Clinical Trial Results:
Risk-based, response-adapted, Phase II open-label trial of nivolumab + brentuximab vedotin (N+ Bv) for children, adolescents, and young adults with relapsed/refractory (R/R) CD30 + classic Hodgkin lymphoma (cHL) after failure of first-line therapy, followed by brentuximab + bendamustine (Bv + B) for participants with a suboptimal response.
CheckMate 744: CHECKpoint pathway and nivolumab clinical Trial Evaluation
Summary
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EudraCT number |
2016-002347-41 |
Trial protocol |
CZ ES IE DE GB NL PL Outside EU/EEA IT |
Global end of trial date |
28 May 2024
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Results information
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Results version number |
v1(current) |
This version publication date |
17 Nov 2024
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First version publication date |
17 Nov 2024
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Other versions |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
CA209-744
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT02927769 | ||
WHO universal trial number (UTN) |
- | ||
Sponsors
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Sponsor organisation name |
Bristol-Myers Squibb
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Sponsor organisation address |
Chaussee de la Hulpe 185, Brussels, Belgium, 1170
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Public contact |
EU Study Start-Up Unit, Bristol-Myers Squibb International Corporation, Clinical.Trials@bms.com
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Scientific contact |
Bristol-Myers Squibb Study Director, Bristol-Myers Squibb, Clinical.Trials@bms.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
Yes
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EMA paediatric investigation plan number(s) |
EMEA-001407-PIP02-15 | ||
Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
Yes
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
08 Jul 2024
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
28 May 2024
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
To describe the complete metabolic response (CMR) rate before radiation therapy/high-dose chemotherapy/autologous stem-cell transplant and event-free survival (EFS) rate at 3 years, as assessed by blinded independent central review (BICR), using Lugano 2014 response criteria.
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Protection of trial subjects |
The study was in compliance with the ethical principles derived from the Declaration of Helsinki and in compliance with all International Conference on Harmonization Good Clinical Practice Guidelines. All the local regulatory requirements pertinent to safety of trial participants were followed.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
28 Mar 2017
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
Yes
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
France: 14
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Country: Number of subjects enrolled |
Germany: 10
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Country: Number of subjects enrolled |
Ireland: 2
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Country: Number of subjects enrolled |
Italy: 15
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Country: Number of subjects enrolled |
Netherlands: 6
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Country: Number of subjects enrolled |
Spain: 1
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Country: Number of subjects enrolled |
United Kingdom: 4
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Country: Number of subjects enrolled |
United States: 20
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Worldwide total number of subjects |
72
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EEA total number of subjects |
48
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
7
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Adolescents (12-17 years) |
42
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Adults (18-64 years) |
23
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From 65 to 84 years |
0
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85 years and over |
0
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Recruitment
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Recruitment details |
- | ||||||||||||||||||
Pre-assignment
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Screening details |
All participants entered the Induction phase. Participants entered the Intensification phase if they received brentuximab + bendamustine (Bv + B). Participants entered the Consolidation Phase if they received radiation therapy (C1) or high-dose chemotherapy/autologous stem cell transplant (HDCT/ASCT) (C2). | ||||||||||||||||||
Period 1
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Period 1 title |
Induction Phase
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Is this the baseline period? |
Yes | ||||||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Not blinded | ||||||||||||||||||
Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Cohort 1: Relapsed/Refractory cHL - Low Risk Relapse | ||||||||||||||||||
Arm description |
Participants started in the induction phase and received nivolumab + brentuximab vedotin (N+Bv) for 2 cycles (6 weeks). Participants with radiographic progression, by Investigator at Cycle 2 entered follow-up. The rest continued in the induction phase and received 2 more cycles of N+Bv (total 4 cycles = 12 weeks). - Participants who had a complete metabolic response (CMR) by BICR after a total of 4 cycles (12 weeks) of N+Bv received 2 more cycles of treatment of N+Bv (total of 6 cycles [18 weeks]), followed by Radiation Therapy (RT) (consolidation phase). - Participants without a CMR after 4 cycles of N+Bv, by BICR, entered the intensification phase and received 2 cycles of brentuximab + bendamustine (Bv+B); participants who achieved CMR after these 2 cycles proceeded with RT (consolidation phase). - Participants who had radiographic progression after Cycle 4 N+Bv, by BICR, or those who did not achieve CMR, after 2 cycles of Bv+B were taken off study treatment and entered follow-up. | ||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||
Investigational medicinal product name |
Brentuximab Vedotin
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Powder for solution for injection
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Routes of administration |
Intravenous use
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Dosage and administration details |
1.8 mg/kg every 21 days
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Investigational medicinal product name |
Nivolumab
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Investigational medicinal product code |
BMS-936558
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Other name |
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Pharmaceutical forms |
Concentrate for solution for injection/infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
3 mg/kg every 21 days
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Arm title
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Cohort 2: Relapsed/Refractory cHL - Standard Risk Relapse | ||||||||||||||||||
Arm description |
Participants started in the induction phase and received nivolumab + brentuximab vedotin (N+Bv) for 2 cycles (6 weeks). Those with progression at Cycle 2 entered follow-up. The rest received 2 more cycles of N+Bv (total 4 cycles = 12 weeks). - Participants with complete metabolic response (CMR) after 4 cycles of N+Bv received high-dose chemotherapy and autologous stem cell transplant (HDCT/ASCT) (consolidation phase). Participants with CMR could receive up to 2 more cycles of N+Bv if their HDCT/ASCT was postponed. - Participants without CMR after 4 cycles of N+Bv received 2 cycles of brentuximab + bendamustine (Bv+B) (intensification phase). - Participants in CMR after 2 cycles of Bv+B received HDCT/ASCT. - Participants without CMR could receive 2 more cycles of Bv+B. If they had CMR, they received HDCT/ASCT. - Participants with CMR could receive up to 2 more cycles of B+Bv if their HDCT/ASCT was postponed. - Participants with progression after Cycle 4 N+Bv were taken off treatment. | ||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||
Investigational medicinal product name |
Bendamustine
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Concentrate for solution for injection
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Routes of administration |
Intravenous use
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Dosage and administration details |
90 mg/m2/day, 21-day cycles (on Days1 and 2)
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Investigational medicinal product name |
Nivolumab
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Investigational medicinal product code |
BMS-936558
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Other name |
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Pharmaceutical forms |
Concentrate for solution for injection/infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
3 mg/kg every 21 days
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Period 2
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Period 2 title |
Consolidation Phase
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Is this the baseline period? |
No | ||||||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Not blinded | ||||||||||||||||||
Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Cohort 1: Relapsed/Refractory cHL - Low Risk Relapse | ||||||||||||||||||
Arm description |
Participants started in the induction phase and received nivolumab + brentuximab vedotin (N+Bv) for 2 cycles (6 weeks). Participants with radiographic progression, by Investigator at Cycle 2 entered follow-up. The rest continued in the induction phase and received 2 more cycles of N+Bv (total 4 cycles = 12 weeks). - Participants who had a complete metabolic response (CMR) by BICR after a total of 4 cycles (12 weeks) of N+Bv received 2 more cycles of treatment of N+Bv (total of 6 cycles [18 weeks]), followed by Radiation Therapy (RT) (consolidation phase). - Participants without a CMR after 4 cycles of N+Bv, by BICR, entered the intensification phase and received 2 cycles of brentuximab + bendamustine (Bv+B); participants who achieved CMR after these 2 cycles proceeded with RT (consolidation phase). - Participants who had radiographic progression after Cycle 4 N+Bv, by BICR, or those who did not achieve CMR, after 2 cycles of Bv+B were taken off study treatment and entered follow-up. | ||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||
Investigational medicinal product name |
Nivolumab
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Investigational medicinal product code |
BMS-936558
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Other name |
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Pharmaceutical forms |
Concentrate for solution for injection/infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
3 mg/kg every 21 days
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Investigational medicinal product name |
Bendamustine
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Investigational medicinal product code |
|||||||||||||||||||
Other name |
|||||||||||||||||||
Pharmaceutical forms |
Concentrate for solution for injection
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Routes of administration |
Intravenous use
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Dosage and administration details |
90 mg/m2/day, 21-day cycles (on Days1 and 2)
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Investigational medicinal product name |
Brentuximab Vedotin
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Investigational medicinal product code |
|||||||||||||||||||
Other name |
|||||||||||||||||||
Pharmaceutical forms |
Powder for solution for injection
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Routes of administration |
Intravenous use
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Dosage and administration details |
1.8 mg/kg every 21 days
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Arm title
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Cohort 2: Relapsed/Refractory cHL - Standard Risk Relapse | ||||||||||||||||||
Arm description |
Participants started in the induction phase and received nivolumab + brentuximab vedotin (N+Bv) for 2 cycles (6 weeks). Those with progression at Cycle 2 entered follow-up. The rest received 2 more cycles of N+Bv (total 4 cycles = 12 weeks). - Participants with complete metabolic response (CMR) after 4 cycles of N+Bv received high-dose chemotherapy and autologous stem cell transplant (HDCT/ASCT) (consolidation phase). Participants with CMR could receive up to 2 more cycles of N+Bv if their HDCT/ASCT was postponed. - Participants without CMR after 4 cycles of N+Bv received 2 cycles of brentuximab + bendamustine (Bv+B) (intensification phase). - Participants in CMR after 2 cycles of Bv+B received HDCT/ASCT. - Participants without CMR could receive 2 more cycles of Bv+B. If they had CMR, they received HDCT/ASCT. - Participants with CMR could receive up to 2 more cycles of B+Bv if their HDCT/ASCT was postponed. - Participants with progression after Cycle 4 N+Bv were taken off treatment. | ||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||
Investigational medicinal product name |
Nivolumab
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Investigational medicinal product code |
BMS-936558
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Other name |
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Pharmaceutical forms |
Concentrate for solution for injection/infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
3 mg/kg every 21 days
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Investigational medicinal product name |
Bendamustine
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Investigational medicinal product code |
|||||||||||||||||||
Other name |
|||||||||||||||||||
Pharmaceutical forms |
Concentrate for solution for injection
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Routes of administration |
Intravenous use
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||||||||||||||||||
Dosage and administration details |
90 mg/m2/day, 21-day cycles (on Days1 and 2)
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||||||||||||||||||
Investigational medicinal product name |
Bendamustine
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||||||||||||||||||
Investigational medicinal product code |
|||||||||||||||||||
Other name |
|||||||||||||||||||
Pharmaceutical forms |
Concentrate for solution for injection
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Routes of administration |
Intravenous use
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Dosage and administration details |
90 mg/m2/day, 21-day cycles (on Days1 and 2)
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Notes [1] - The number of subjects starting the period is not consistent with the number completing the preceding period. It is expected the number of subjects starting the subsequent period will be the same as the number completing the preceding period. Justification: Not all participants who started in the induction phase entered the intensification or consolidation phase. |
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Period 3
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Period 3 title |
Intensification Phase
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Is this the baseline period? |
No | ||||||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Not blinded | ||||||||||||||||||
Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Cohort 1: Relapsed/Refractory cHL - Low Risk Relapse | ||||||||||||||||||
Arm description |
Participants started in the induction phase and received nivolumab + brentuximab vedotin (N+Bv) for 2 cycles (6 weeks). Participants with radiographic progression, by Investigator at Cycle 2 entered follow-up. The rest continued in the induction phase and received 2 more cycles of N+Bv (total 4 cycles = 12 weeks). - Participants who had a complete metabolic response (CMR) by BICR after a total of 4 cycles (12 weeks) of N+Bv received 2 more cycles of treatment of N+Bv (total of 6 cycles [18 weeks]), followed by Radiation Therapy (RT) (consolidation phase). - Participants without a CMR after 4 cycles of N+Bv, by BICR, entered the intensification phase and received 2 cycles of brentuximab + bendamustine (Bv+B); participants who achieved CMR after these 2 cycles proceeded with RT (consolidation phase). - Participants who had radiographic progression after Cycle 4 N+Bv, by BICR, or those who did not achieve CMR, after 2 cycles of Bv+B were taken off study treatment and entered follow-up. | ||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||
Investigational medicinal product name |
Bendamustine
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Investigational medicinal product code |
|||||||||||||||||||
Other name |
|||||||||||||||||||
Pharmaceutical forms |
Concentrate for solution for injection
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Routes of administration |
Intravenous use
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Dosage and administration details |
90 mg/m2/day, 21-day cycles (on Days1 and 2)
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Investigational medicinal product name |
Brentuximab Vedotin
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Investigational medicinal product code |
|||||||||||||||||||
Other name |
|||||||||||||||||||
Pharmaceutical forms |
Powder for solution for injection
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Routes of administration |
Intravenous use
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Dosage and administration details |
1.8 mg/kg every 21 days
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Arm title
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Cohort 2: Relapsed/Refractory cHL - Standard Risk Relapse | ||||||||||||||||||
Arm description |
Participants started in the induction phase and received nivolumab + brentuximab vedotin (N+Bv) for 2 cycles (6 weeks). Those with progression at Cycle 2 entered follow-up. The rest received 2 more cycles of N+Bv (total 4 cycles = 12 weeks). - Participants with complete metabolic response (CMR) after 4 cycles of N+Bv received high-dose chemotherapy and autologous stem cell transplant (HDCT/ASCT) (consolidation phase). Participants with CMR could receive up to 2 more cycles of N+Bv if their HDCT/ASCT was postponed. - Participants without CMR after 4 cycles of N+Bv received 2 cycles of brentuximab + bendamustine (Bv+B) (intensification phase). - Participants in CMR after 2 cycles of Bv+B received HDCT/ASCT. - Participants without CMR could receive 2 more cycles of Bv+B. If they had CMR, they received HDCT/ASCT. - Participants with CMR could receive up to 2 more cycles of B+Bv if their HDCT/ASCT was postponed. - Participants with progression after Cycle 4 N+Bv were taken off treatment. | ||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||
Investigational medicinal product name |
Bendamustine
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Investigational medicinal product code |
|||||||||||||||||||
Other name |
|||||||||||||||||||
Pharmaceutical forms |
Concentrate for solution for injection
|
||||||||||||||||||
Routes of administration |
Intravenous use
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Dosage and administration details |
90 mg/m2/day, 21-day cycles (on Days1 and 2)
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||||||||||||||||||
Investigational medicinal product name |
Brentuximab Vedotin
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||||||||||||||||||
Investigational medicinal product code |
|||||||||||||||||||
Other name |
|||||||||||||||||||
Pharmaceutical forms |
Powder for solution for injection
|
||||||||||||||||||
Routes of administration |
Intravenous use
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Dosage and administration details |
1.8 mg/kg every 21 days
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Notes [2] - The number of subjects starting the period is not consistent with the number completing the preceding period. It is expected the number of subjects starting the subsequent period will be the same as the number completing the preceding period. Justification: Not all participants who started in the induction phase entered the intensification or consolidation phase. |
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Baseline characteristics reporting groups
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Reporting group title |
Cohort 1: Relapsed/Refractory cHL - Low Risk Relapse
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Reporting group description |
Participants started in the induction phase and received nivolumab + brentuximab vedotin (N+Bv) for 2 cycles (6 weeks). Participants with radiographic progression, by Investigator at Cycle 2 entered follow-up. The rest continued in the induction phase and received 2 more cycles of N+Bv (total 4 cycles = 12 weeks). - Participants who had a complete metabolic response (CMR) by BICR after a total of 4 cycles (12 weeks) of N+Bv received 2 more cycles of treatment of N+Bv (total of 6 cycles [18 weeks]), followed by Radiation Therapy (RT) (consolidation phase). - Participants without a CMR after 4 cycles of N+Bv, by BICR, entered the intensification phase and received 2 cycles of brentuximab + bendamustine (Bv+B); participants who achieved CMR after these 2 cycles proceeded with RT (consolidation phase). - Participants who had radiographic progression after Cycle 4 N+Bv, by BICR, or those who did not achieve CMR, after 2 cycles of Bv+B were taken off study treatment and entered follow-up. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Cohort 2: Relapsed/Refractory cHL - Standard Risk Relapse
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Reporting group description |
Participants started in the induction phase and received nivolumab + brentuximab vedotin (N+Bv) for 2 cycles (6 weeks). Those with progression at Cycle 2 entered follow-up. The rest received 2 more cycles of N+Bv (total 4 cycles = 12 weeks). - Participants with complete metabolic response (CMR) after 4 cycles of N+Bv received high-dose chemotherapy and autologous stem cell transplant (HDCT/ASCT) (consolidation phase). Participants with CMR could receive up to 2 more cycles of N+Bv if their HDCT/ASCT was postponed. - Participants without CMR after 4 cycles of N+Bv received 2 cycles of brentuximab + bendamustine (Bv+B) (intensification phase). - Participants in CMR after 2 cycles of Bv+B received HDCT/ASCT. - Participants without CMR could receive 2 more cycles of Bv+B. If they had CMR, they received HDCT/ASCT. - Participants with CMR could receive up to 2 more cycles of B+Bv if their HDCT/ASCT was postponed. - Participants with progression after Cycle 4 N+Bv were taken off treatment. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Cohort 1: Relapsed/Refractory cHL - Low Risk Relapse
|
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Reporting group description |
Participants started in the induction phase and received nivolumab + brentuximab vedotin (N+Bv) for 2 cycles (6 weeks). Participants with radiographic progression, by Investigator at Cycle 2 entered follow-up. The rest continued in the induction phase and received 2 more cycles of N+Bv (total 4 cycles = 12 weeks). - Participants who had a complete metabolic response (CMR) by BICR after a total of 4 cycles (12 weeks) of N+Bv received 2 more cycles of treatment of N+Bv (total of 6 cycles [18 weeks]), followed by Radiation Therapy (RT) (consolidation phase). - Participants without a CMR after 4 cycles of N+Bv, by BICR, entered the intensification phase and received 2 cycles of brentuximab + bendamustine (Bv+B); participants who achieved CMR after these 2 cycles proceeded with RT (consolidation phase). - Participants who had radiographic progression after Cycle 4 N+Bv, by BICR, or those who did not achieve CMR, after 2 cycles of Bv+B were taken off study treatment and entered follow-up. | ||
Reporting group title |
Cohort 2: Relapsed/Refractory cHL - Standard Risk Relapse
|
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Reporting group description |
Participants started in the induction phase and received nivolumab + brentuximab vedotin (N+Bv) for 2 cycles (6 weeks). Those with progression at Cycle 2 entered follow-up. The rest received 2 more cycles of N+Bv (total 4 cycles = 12 weeks). - Participants with complete metabolic response (CMR) after 4 cycles of N+Bv received high-dose chemotherapy and autologous stem cell transplant (HDCT/ASCT) (consolidation phase). Participants with CMR could receive up to 2 more cycles of N+Bv if their HDCT/ASCT was postponed. - Participants without CMR after 4 cycles of N+Bv received 2 cycles of brentuximab + bendamustine (Bv+B) (intensification phase). - Participants in CMR after 2 cycles of Bv+B received HDCT/ASCT. - Participants without CMR could receive 2 more cycles of Bv+B. If they had CMR, they received HDCT/ASCT. - Participants with CMR could receive up to 2 more cycles of B+Bv if their HDCT/ASCT was postponed. - Participants with progression after Cycle 4 N+Bv were taken off treatment. | ||
Reporting group title |
Cohort 1: Relapsed/Refractory cHL - Low Risk Relapse
|
||
Reporting group description |
Participants started in the induction phase and received nivolumab + brentuximab vedotin (N+Bv) for 2 cycles (6 weeks). Participants with radiographic progression, by Investigator at Cycle 2 entered follow-up. The rest continued in the induction phase and received 2 more cycles of N+Bv (total 4 cycles = 12 weeks). - Participants who had a complete metabolic response (CMR) by BICR after a total of 4 cycles (12 weeks) of N+Bv received 2 more cycles of treatment of N+Bv (total of 6 cycles [18 weeks]), followed by Radiation Therapy (RT) (consolidation phase). - Participants without a CMR after 4 cycles of N+Bv, by BICR, entered the intensification phase and received 2 cycles of brentuximab + bendamustine (Bv+B); participants who achieved CMR after these 2 cycles proceeded with RT (consolidation phase). - Participants who had radiographic progression after Cycle 4 N+Bv, by BICR, or those who did not achieve CMR, after 2 cycles of Bv+B were taken off study treatment and entered follow-up. | ||
Reporting group title |
Cohort 2: Relapsed/Refractory cHL - Standard Risk Relapse
|
||
Reporting group description |
Participants started in the induction phase and received nivolumab + brentuximab vedotin (N+Bv) for 2 cycles (6 weeks). Those with progression at Cycle 2 entered follow-up. The rest received 2 more cycles of N+Bv (total 4 cycles = 12 weeks). - Participants with complete metabolic response (CMR) after 4 cycles of N+Bv received high-dose chemotherapy and autologous stem cell transplant (HDCT/ASCT) (consolidation phase). Participants with CMR could receive up to 2 more cycles of N+Bv if their HDCT/ASCT was postponed. - Participants without CMR after 4 cycles of N+Bv received 2 cycles of brentuximab + bendamustine (Bv+B) (intensification phase). - Participants in CMR after 2 cycles of Bv+B received HDCT/ASCT. - Participants without CMR could receive 2 more cycles of Bv+B. If they had CMR, they received HDCT/ASCT. - Participants with CMR could receive up to 2 more cycles of B+Bv if their HDCT/ASCT was postponed. - Participants with progression after Cycle 4 N+Bv were taken off treatment. | ||
Reporting group title |
Cohort 1: Relapsed/Refractory cHL - Low Risk Relapse
|
||
Reporting group description |
Participants started in the induction phase and received nivolumab + brentuximab vedotin (N+Bv) for 2 cycles (6 weeks). Participants with radiographic progression, by Investigator at Cycle 2 entered follow-up. The rest continued in the induction phase and received 2 more cycles of N+Bv (total 4 cycles = 12 weeks). - Participants who had a complete metabolic response (CMR) by BICR after a total of 4 cycles (12 weeks) of N+Bv received 2 more cycles of treatment of N+Bv (total of 6 cycles [18 weeks]), followed by Radiation Therapy (RT) (consolidation phase). - Participants without a CMR after 4 cycles of N+Bv, by BICR, entered the intensification phase and received 2 cycles of brentuximab + bendamustine (Bv+B); participants who achieved CMR after these 2 cycles proceeded with RT (consolidation phase). - Participants who had radiographic progression after Cycle 4 N+Bv, by BICR, or those who did not achieve CMR, after 2 cycles of Bv+B were taken off study treatment and entered follow-up. | ||
Reporting group title |
Cohort 2: Relapsed/Refractory cHL - Standard Risk Relapse
|
||
Reporting group description |
Participants started in the induction phase and received nivolumab + brentuximab vedotin (N+Bv) for 2 cycles (6 weeks). Those with progression at Cycle 2 entered follow-up. The rest received 2 more cycles of N+Bv (total 4 cycles = 12 weeks). - Participants with complete metabolic response (CMR) after 4 cycles of N+Bv received high-dose chemotherapy and autologous stem cell transplant (HDCT/ASCT) (consolidation phase). Participants with CMR could receive up to 2 more cycles of N+Bv if their HDCT/ASCT was postponed. - Participants without CMR after 4 cycles of N+Bv received 2 cycles of brentuximab + bendamustine (Bv+B) (intensification phase). - Participants in CMR after 2 cycles of Bv+B received HDCT/ASCT. - Participants without CMR could receive 2 more cycles of Bv+B. If they had CMR, they received HDCT/ASCT. - Participants with CMR could receive up to 2 more cycles of B+Bv if their HDCT/ASCT was postponed. - Participants with progression after Cycle 4 N+Bv were taken off treatment. |
|
|||||||||
End point title |
Complete Metabolic Response (CMR) Rate at Any Time Prior to Radiation Therapy by Blinded Independent Centralized Review (BICR) - Cohort 1 [1] [2] | ||||||||
End point description |
The complete metabolic response (CMR) rate is defined as the percent of all response-evaluable participants who, assessed by the BICR, achieved best response of CMR.
Complete metabolic response (CMR):
• Lymph nodes/extralymphatic sites: Score 1, 2, 3 with/without residual mass on 5-point scale
• New lesions: No
• Bone marrow: No FDG-avid disease
Participants who stopped study treatment early for toxicity without a CMR were evaluable.
Confidence interval is based on the Clopper and Pearson method
|
||||||||
End point type |
Primary
|
||||||||
End point timeframe |
From first dose to complete metabolic response or the completion of six cycles of therapy (up to approximately 18 weeks).
|
||||||||
Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Only descriptive statistics were planned for this endpoint. [2] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Prespecified to be collected for Cohort 1 only. |
|||||||||
|
|||||||||
No statistical analyses for this end point |
|
|||||||||
End point title |
Event-free Survival (EFS) Rate at 3 Years by Blinded Independent Centralized Review (BICR) - Cohort 1 [3] [4] | ||||||||
End point description |
Event Free Survival (EFS) is the time from the first treatment to the earliest occurrence of composite events including: Disease progression (PD), Failure to achieve complete metabolic response (CMR) after 4 cycles of N+Bv and 2 cycles of Bv+B, Secondary malignancy, Death .
PD :
Lymph Nodes and Lesions: new growth or increase of >= 50% in size from nadir. New or growing lesions outside the lymph nodes.
Spleen: Significant increase in spleen size, either from a previously enlarged state or from normal size.
New Lesions: Yes
Bone Marrow: New or returning FDG-avid disease
CM):
Lymph nodes/extralymphatic sites: Score 1, 2, 3 with/without residual mass on 5-point scale •
New lesions: No
Bone marrow: No FDG-avid disease
Participants without an “event” were censored at the last tumor assessment. Those who started subsequent anticancer therapy without a prior “event” were censored at the last tumor assessment prior to or upon starting subsequent therapy.
Based on Kaplan-Meier Estimates.
|
||||||||
End point type |
Primary
|
||||||||
End point timeframe |
At 3 years post first dose of study therapy
|
||||||||
Notes [3] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Only descriptive statistics were planned for this endpoint. [4] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Prespecified to be collected for Cohort 1 only. |
|||||||||
|
|||||||||
No statistical analyses for this end point |
|
|||||||||
End point title |
Complete Metabolic Response (CMR) Rate at Any Time Prior to High Dose Chemotherapy Followed by Autologous Stem Cell Treatment (HDCT/ASCT) by Blinded Independent Centralized Review (BICR) - Cohort 2 [5] [6] | ||||||||
End point description |
The complete metabolic response (CMR) rate is defined as the percent of all response-evaluable participants who, assessed by the BICR, achieved best response of CMR.
Complete metabolic response (CMR):
• Lymph nodes/extralymphatic sites: Score 1, 2, 3 with/without residual mass on 5-point scale
• New lesions: No
• Bone marrow: No FDG-avid disease
Participants who came off study treatment early for toxicity without a CMR were evaluable.
Confidence interval is based on the Clopper and Pearson method
|
||||||||
End point type |
Primary
|
||||||||
End point timeframe |
From first dose to complete metabolic response or the completion of six cycles of therapy (up to approximately 18 weeks)
|
||||||||
Notes [5] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Only descriptive statistics were planned for this endpoint. [6] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Prespecified to be collected for Cohort 1 only. |
|||||||||
|
|||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Overall Response Rate (ORR) Following 4 Cycles of Nivolumab + Brentuximab Vedotin Treatment by Blinded Independent Centralized Review (BICR) | ||||||||||||
End point description |
Overall response rate (ORR) is defined as the percent of all response-evaluable participants who, assessed by the BICR, achieved a best response of complete metabolic response (CMR) or partial metabolic response (PMR).
Complete metabolic response (CMR):
• Lymph nodes/extralymphatic sites: Score 1, 2, 3 with/without residual mass on 5-point scale
• New lesions: No
• Bone marrow: No FDG-avid disease
Partial metabolic response (PMR):
• Lymph nodes/extralymphatic: Score 4 or 5, reduced uptake from baseline
• New lesions: None
• Bone marrow: Residual uptake higher than normal, reduced from baseline.
Participants who came off early for toxicity without CMR or PMR were evaluable.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
From first dose to PMR or CMR within 4 cycles of therapy, or the completion of four cycles of therapy (N+Bv x4) (up to approximately 12 weeks).
|
||||||||||||
|
|||||||||||||
No statistical analyses for this end point |
|
|||||||||
End point title |
Event-free Survival (EFS) Rate at 3 Years by Investigator - Cohort 1 [7] | ||||||||
End point description |
Event Free Survival (EFS) is the time from the first treatment to the earliest occurrence of composite events including: Disease progression (PD), Failure to achieve complete metabolic response (CMR) after 4 cycles of N+Bv and 2 cycles of Bv+B, Secondary malignancy, Death .
PD :
Lymph Nodes and Lesions: new growth or increase of >= 50% in size from nadir. New or growing lesions outside the lymph nodes.
Spleen: Significant increase in spleen size, either from a previously enlarged state or from normal size.
New Lesions: Yes
Bone Marrow: New or returning FDG-avid disease
CMR:
Lymph nodes/extralymphatic sites: Score 1, 2, 3 with/without residual mass on 5-point scale
New lesions: No
Bone marrow: No FDG-avid disease
Participants without an “event” were censored at the last tumor assessment. Those who started subsequent anticancer therapy without a prior “event” were censored at the last tumor assessment prior to or upon starting subsequent therapy.
Based on Kaplan-Meier Estimates.
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
At 3 years post first dose of study therapy
|
||||||||
Notes [7] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Prespecified to be collected for Cohort 1 only. |
|||||||||
|
|||||||||
No statistical analyses for this end point |
|
|||||||||
End point title |
Complete Metabolic Response (CMR) Rate at Any Time Prior to Radiation Therapy by Investigator - Cohort 1 [8] | ||||||||
End point description |
The complete metabolic response (CMR) rate is defined as the percent of all response-evaluable participants who, assessed by the investigator, achieved best response of CMR.
Complete metabolic response (CMR):
• Lymph nodes/extralymphatic sites: Score 1, 2, 3 with/without residual mass on 5-point scale
• New lesions: No
• Bone marrow: No FDG-avid disease
Participants who come off early for toxicity without a CMR were evaluable.
Confidence interval is based on the Clopper and Pearson method
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
From first dose to complete metabolic response or the completion of six cycles of therapy (up to approximately 18 weeks).
|
||||||||
Notes [8] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Prespecified to be collected for Cohort 1 only. |
|||||||||
|
|||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Duration of Response (DOR) by Blinded Independent Centralized Review (BICR) | ||||||||||||
End point description |
Duration of response (DOR) is from first complete metabolic response or partial metabolic response (CMR or PMR) to event free survival EFS (Cohort 1)/progression free survival PFS (Cohort 2) event. For participants with no event, the DOR was censored on the date of last tumor assessment.
Participants who started subsequent anticancer therapy (not part of high-dose chemotherapy followed by autologous stem cell transplant HDCT/ASCT) without a prior reported EFS/PFS event were censored at the last tumor assessment prior to starting subsequent anticancer therapy.
Complete metabolic response (CMR):
• Lymph nodes/extralymphatic sites: Score 1, 2, 3 with/without residual mass on 5-point scale
• New lesions: No
• Bone marrow: No FDG-avid disease
Partial metabolic response:
• Lymph nodes/extralymphatic: Score 4 or 5, reduced uptake from baseline
• New lesions: None
• Bone marrow: Residual uptake higher than normal, reduced from baseline.
Based on Kaplan-Meier estimates. "99999 = N/A".
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
From first dose until disease progression, start of subsequent anti-cancer therapy, or or death due to any cause (up to approximately 86 months)
|
||||||||||||
|
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Progression Free Survival (PFS) Rate at 3 Years by Blinded Independent Centralized Review (BICR) | ||||||||||||
End point description |
Progression Free Survival (PFS) is the time from the date of first treatment to the date of first documented disease progression by BICR or death.
Progressive Disease (PD):
Lymph Nodes and Lesions: new growth or increase of >= 50% in size from nadir. New or growing lesions outside the lymph nodes.
Spleen: Significant increase in spleen size, either from a previously enlarged state or from normal size.
New Lesions: Yes
Bone Marrow: New or returning FDG-avid disease.
Participants who neither progressed nor died were censored at the last adequate tumor assessment. Participants who started subsequent anticancer therapy (that is not part of high dose chemotherapy followed by autologous stem cell transplant (HDCT/ASCT) Consolidation Therapy for R2 Cohort) without a prior reported progression or death were censored at the last tumor assessment prior to initiation of the subsequent anticancer therapy.
Based on Kaplan-Meier Estimates.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
At 3 years post first dose of study therapy
|
||||||||||||
|
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Progression Free Survival (PFS) Rate at 3 Years by Investigator | ||||||||||||
End point description |
Progression Free Survival (PFS) is the time from the date of first treatment to the date of first documented disease progression by investigator or death.
Progressive Disease (PD):
Lymph Nodes and Lesions: new growth or increase of >= 50% in size from nadir. New or growing lesions outside the lymph nodes.
Spleen: Significant increase in spleen size, either from a previously enlarged state or from normal size.
New Lesions: Yes
Bone Marrow: New or returning FDG-avid disease.
Participants who neither progressed nor died were be censored at the last adequate tumor assessment. Participants who started subsequent anticancer therapy (that is not part of high dose chemotherapy followed by autologous stem cell transplant (HDCT/ASCT) Consolidation Therapy forR2 Cohort) without a prior reported progression or death were censored at the last tumor assessment prior to initiation of the subsequent anticancer therapy.
Based on Kaplan-Meier Estimates.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
At 3 years post first dose
|
||||||||||||
|
|||||||||||||
No statistical analyses for this end point |
|
|||||||||
End point title |
Complete Metabolic Response (CMR) Rate at Any Time Prior to High Dose Chemotherapy Followed by Autologous Stem Cell Treatment (HDCT/ASCT) by Investigator - Cohort 2 [9] | ||||||||
End point description |
The complete metabolic response (CMR) rate is defined as the percent of all response-evaluable participants who, assessed by the investigator, achieved best response of CMR.
Complete metabolic response (CMR):
• Lymph nodes/extralymphatic sites: Score 1, 2, 3 with/without residual mass on 5-point scale
• New lesions: No
• Bone marrow: No FDG-avid disease
Participants who came off study treatment early for toxicity without a CMR were evaluable.
Confidence interval is based on the Clopper and Pearson method.
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
From first dose to complete metabolic response or the completion of six cycles of therapy (up to approximately 18 weeks)
|
||||||||
Notes [9] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Prespecified to be collected for Cohort 2 only. |
|||||||||
|
|||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Overall Response Rate (ORR) Following 4 Cycles of Nivolumab + Brentuximab Vedotin Treatment by Investigator | ||||||||||||
End point description |
Overall response rate (ORR) is defined as the percent of all response-evaluable participants who, assessed by the investigator, achieve a best response of complete metabolic response (CMR) or partial metabolic response (PMR).
Complete metabolic response (CMR):
• Lymph nodes/extralymphatic sites: Score 1, 2, 3 with/without residual mass on 5-point scale
• New lesions: No
• Bone marrow: No FDG-avid disease
Partial metabolic response:
• Lymph nodes/extralymphatic: Score 4 or 5, reduced uptake from baseline
• New lesions: None
• Bone marrow: Residual uptake higher than normal, reduced from baseline
Participants who came off early for toxicity without CMR or PMR were evaluable.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
From first dose to PMR or CMR within 4 cycles of therapy, or the completion of four cycles of therapy (N+Bv x4) (up to approximately 12 weeks).
|
||||||||||||
|
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Duration of Response (DOR) by Investigator | ||||||||||||
End point description |
Duration of response (DOR) is from first complete metabolic response or partial metabolic response (CMR or PMR) to event free survival EFS (Cohort 1)/progression free survival PFS (Cohort 2) event. For participants with no event, the DOR was censored on the date of last tumor assessment.
Participants who started subsequent anticancer therapy (not part of high-dose chemotherapy followed by autologous stem cell transplant HDCT/ASCT) without a prior reported EFS/PFS event were censored at the last tumor assessment before starting subsequent anticancer therapy.
Complete metabolic response (CMR):
• Lymph nodes/extralymphatic sites: Score 1, 2, 3 with/without residual mass on 5-point scale
• New lesions: No
• Bone marrow: No FDG-avid disease
Partial metabolic response:
• Lymph nodes/extralymphatic: Score 4 or 5, reduced uptake from baseline
• New lesions: None
• Bone marrow: Residual uptake higher than normal, reduced from baseline.
Based on Kaplan-Meier estimates. "99999=N/A".
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
From first dose until disease progression, start of subsequent anti-cancer therapy, or or death due to any cause (up to approximately 86 months)
|
||||||||||||
|
|||||||||||||
No statistical analyses for this end point |
|
||||||||||
End point title |
The Number of Participants with Adverse Events (AEs) | |||||||||
End point description |
An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered study drug and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (such as an abnormal laboratory finding), symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug.
|
|||||||||
End point type |
Secondary
|
|||||||||
End point timeframe |
From first dose to 30 days post last dose (an average of 4 months up until a maximum of 7 months).
|
|||||||||
|
||||||||||
No statistical analyses for this end point |
|
||||||||||
End point title |
The Number of Participants with Serious Adverse Events (SAEs) | |||||||||
End point description |
A Serious Adverse Event (SAE) is defined as any untoward medical occurrence that, at any dose:
- Results in death
- Is life-threatening (defined as an event in which the participant was at risk of death at the time of the event; it does not refer to an event which hypothetically might have caused death if it were more severe)
- Requires inpatient hospitalization or causes prolongation of existing hospitalization
- Results in persistent or significant disability/incapacity
- Is a congenital anomaly/birth defect
- Is an important medical event.
|
|||||||||
End point type |
Secondary
|
|||||||||
End point timeframe |
From first dose to 30 days post last dose (an average of 4 months up until a maximum of 7 months)
|
|||||||||
|
||||||||||
No statistical analyses for this end point |
|
||||||||||||||||||||||||||||||||||||||||
End point title |
The Number of Participants with Abnormal Laboratory Values for Specific Thyroid Tests | |||||||||||||||||||||||||||||||||||||||
End point description |
The Number of Participants with Abnormal Laboratory Values for Specific Thyroid Tests.
|
|||||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
|||||||||||||||||||||||||||||||||||||||
End point timeframe |
From first dose to 30 days post last dose (an average of 4 months up until a maximum of 7 months)
|
|||||||||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||
End point title |
The Number of Participants with Abnormal Laboratory Values for Liver Tests | ||||||||||||||||||||||||||||||
End point description |
The Number of Participants with Abnormal Laboratory Values for Liver Tests.
|
||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||
End point timeframe |
From first dose to 30 days post last dose (an average of 4 months up until a maximum of 7 months)
|
||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
||||||||||
End point title |
Vital Sign Measurements | |||||||||
End point description |
Data not collected
|
|||||||||
End point type |
Secondary
|
|||||||||
End point timeframe |
Data not collected
|
|||||||||
|
||||||||||
Notes [10] - Data not collected [11] - Data not collected |
||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Adverse events information
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Timeframe for reporting adverse events |
SAEs and Non-serious AEs were assessed from first dose to 30 days after last dose of study therapy (assessed for an average of 4 months up until a maximum of 7 months).
|
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Adverse event reporting additional description |
Serious Adverse Events and Non-Serious Adverse Events represents all participants that received at least 1 dose of study medication.
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
27.0
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Reporting groups
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Reporting group title |
Cohort 1: Nivo + Bv
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Reporting group description |
Participants started in the induction phase and received nivolumab + brentuximab vedotin (N+Bv) for 2 cycles (6 weeks). Participants with radiographic progression, as assessed by Investigator at Cycle 2 entered follow-up. The rest of the participants continued in the induction phase and received 2 additional cycles of N+Bv study therapy (total 4 cycles = 12 weeks). - Participants who had a complete metabolic response (CMR) by BICR after a total of 4 cycles (12 weeks) of N+Bv received an additional 2 cycles of treatment of N+Bv (for a total of 6 cycles [18 weeks]), followed by Radiation Therapy (RT) (consolidation phase). | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Cohort 2: Nivo + Bv
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Reporting group description |
Participants started in the induction phase and received nivolumab + brentuximab vedotin (N+Bv) for 2 cycles (6 weeks). Participants with radiographic progression, as assessed by Investigator at Cycle 2 entered follow-up. The rest of the participants received 2 additional cycles of N+Bv study therapy (total 4 cycles = 12 weeks). - Participants who had complete metabolic response (CMR), by BICR, after a total of 4 cycles (12 weeks) of N+Bv proceeded with high-dose chemotherapy followed by an autologous stem cell transplant (HDCT/ASCT) (consolidation phase). Participants with CMR had the option to receive up to 2 additional cycles of N+Bv if their HDCT/ASCT was postponed for any reason. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Cohort 2: (Nivo + Bv) + (Bv + B)
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Reporting group description |
Participants started in the induction phase with nivolumab and brentuximab vedotin (N+Bv) for 2 cycles (6 weeks). Those with radiographic progression at Cycle 2 entered follow-up. The rest received 2 more cycles of N+Bv (total 4 cycles, 12 weeks). Participants with complete metabolic response (CMR) after 4 cycles of N+Bv got with high-dose chemotherapy and autologous stem cell transplant (HDCT/ASCT). Those with CMR could receive up to 2 additional cycles of N+Bv if HDCT/ASCT was postponed. Participants without CMR after 4 cycles of N+Bv received 2 cycles of brentuximab and bendamustine (Bv+B). Those with CMR after 2 cycles of Bv+B got HDCT/ASCT. Participants without CMR could receive 2 more cycles of Bv+B and, if CMR was attained, got HDCT/ASCT. Those with CMR could receive up to 2 additional cycles of Bv+B if HDCT/ASCT was postponed. Participants with radiographic progression after Cycle 4 N+Bv or no CMR after final Bv+B were taken off study treatment and entered follow-up. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Cohort 1: (Nivo + Bv) + (Bv + B)
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Reporting group description |
Participants started in the induction phase and received nivolumab and brentuximab vedotin (N+Bv) for 2 cycles (6 weeks). Those with radiographic progression at Cycle 2 entered follow-up. The rest continued in the induction phase for 2 additional cycles of N+Bv (total 4 cycles, 12 weeks). Participants with a complete metabolic response (CMR) after 4 cycles of N+Bv received 2 more cycles of N+Bv (total 6 cycles, 18 weeks) followed by Radiation Therapy (RT) in the consolidation phase. Participants without a CMR after 4 cycles of N+Bv entered the intensification phase and received 2 cycles of brentuximab and bendamustine (Bv+B). Those who achieved CMR after these 2 cycles proceeded with RT consolidation. Participants with radiographic progression after Cycle 4 N+Bv or those who did not achieve CMR after 2 cycles of Bv+B were taken off study treatment and entered follow-up. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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01 Mar 2017 |
Per Health Authority recommendations (eg,: Add additional Safety Assessments to provide more frequent safety monitoring for this patient population during Induction Phase, update an optional lab sample and revise Section 2 Tables-due to new Safety Labs, add futility rule for R2 Cohort, amend inclusion criteria language from Direct to Total Bilirubin, simplify
nivolumab dose delay criteria language and formatting, include guidance for live vaccinations, and clarify the need to follow local guidelines for opportunistic infection prophylaxis).
Additionally, clarifying: R1 Consolidation Therapy may be inclusive of all types of Radiation Therapy (RT) per institutional guidelines, adds up to 2 additional cycles of Bv+B with BMS MM approval for R2 cohort consolidation therapy delays (to be consistent with the approach taken for Induction Phase, N+Bv), deletes wording “for biomarker analysis” as the
biopsy isrequired per Standard of Care and provided to BMS for histologic confirmation of disease and biomarker testing, modification of requirements for FDG-PET at screening and during treatment in alignment with Standard of Care practices, and LYRIC 2016 criteria will be added as an exploratory endpoint for future data analysis according to refinement of LUGANO classification in the era of immunomodulatory therapy. |
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26 Mar 2021 |
The response assessment by investigators using Lugano 2014 response criteria was added as a secondary endpoint to allow for a comprehensive interpretation of the study data. Guidance for collection and submission of tumor assessments was added to support the evaluation of this new secondary endpoint.
Contraception requirements for female participants of child bearing potential were modified to properly align with Nivolumab clinical research standard guidelines and brentuximab label. Other minor edits were made, as described in the Summary of Key Changes. |
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Interruptions (globally) |
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Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
None reported |