Clinical Trial Results:
Phase II study to evaluate the efficacy of upfront obinutuzumab in mantle cell lymphoma patients treated by DHAP followed by autologous transplantation plus obinutuzumab maintenance then MRD driven maintenance
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Summary
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EudraCT number |
2016-000548-33 |
Trial protocol |
FR |
Global end of trial date |
02 Dec 2024
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Results information
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Results version number |
v1(current) |
This version publication date |
08 Apr 2026
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First version publication date |
08 Apr 2026
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Other versions |
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Summary report(s) |
synopsis_Protocol V5.0 |
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 |
LyMa101
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT02896582 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
LYSARC
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Sponsor organisation address |
Centre Hospitalier Lyon-Sud Bâtiment 2D, PIERRE-BÉNITE Cedex, France, 69495
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Public contact |
Project Management
, LYSARC, lyma101@lysarc.org
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Scientific contact |
Pr. Steven Le Gouill , LYSA, steven.legouill@curie.fr
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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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? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
02 Dec 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 |
02 Dec 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 evaluate the efficacy of upfront Obinutuzumab (GA101) at the molecular level (MRD) in bone marrow after induction in patients with previously untreated MCL treated by DHAP.
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Protection of trial subjects |
Obinutuzumab must be administered in a clinical (inpatient or outpatient) setting. Full emergency resuscitation facilities should be immediately available and patients should be under close supervision of the investigator at all times
Obinutuzumab should be administered as a slow IV infusion through a dedicated line and after premedications.
The infusion rate of the first GA101 administration is up by 50 mg/hour every thirty minutes until 400 mg/hour to manage potential infusion related reactions or hypersensitivity reactions. For patients who are considered to be at risk of tumor lysis syndrome (TLS) with a high lymphocyte count or bulky lymphoadenopathy, the infusion have to be given extremely slowly (25 mg/hour) over a long period of time or the dose may be split
and given over more than one day. The first recommended dosage is 100 mg followed by 900mg administered on day 1 or day 2. All patients considered at risk should be carefully monitored during the initial days of treatment with a special focus on renal function, potassium, and uric acid values.
The therapy with anti-CD 20 antibodies (obinutuzumab) should be discontinued during the investigations of a
potential PML (Progressive Multifocal Leukoencephalopathy) and permanently stopped if the diagnosis of PML is confirmed. Discontinuation or reduction of any concomitant chemotherapy or immunosuppressive therapy should also be considered
As supportive cares:
G-CSF administration is required during treatment cycles and stem cell collections.
Platelet and red blood cell transfusions are permitted, as necessary.
The use of antibiotics and other supportive therapies is in the discretion of the treating physician.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
15 Sep 2016
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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: 86
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Worldwide total number of subjects |
86
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EEA total number of subjects |
86
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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) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
86
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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 |
All 86 patients included in the study were enrolled in France between November 2016 and 02 May 2018. | ||||||||||||||||||||||||||||||
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Pre-assignment
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Screening details |
Number of patients screened : 88 Number of patients enrolled : 86 | ||||||||||||||||||||||||||||||
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Period 1
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Period 1 title |
Treatment (overall period)
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Is this the baseline period? |
Yes | ||||||||||||||||||||||||||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | ||||||||||||||||||||||||||||||
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Arms
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Arm title
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GA101 | ||||||||||||||||||||||||||||||
Arm description |
Patients receive 4 cycles of GA-DHAP every 21 days and patients at least in stable disease after induction are transplanted. After ASCT, patients at least in stable disease receive a maintenance : Obinutuzumab every 2 months for 3 years. The patients with an informative MRD at baseline will continue with 3 additional years of maintenance in wich the patients will receive Obinutuzumab according to their MRD status. | ||||||||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||||||||
Investigational medicinal product name |
Obinutuzumab
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Infusion
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Routes of administration |
Infusion
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Dosage and administration details |
Patients will receive their first Obinutuzumab infusion (1000 mg) on Day 1 (Cycle 1 Day 1) along with standard premedication. During Cycle 1, Obinutuzumab will also be administered on Days 8 and 15.
Cycle 2 to 4: one administration (1000 mg) every 21 days.
Maintenance : 1000 mg every 2 months.
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Baseline characteristics reporting groups
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Reporting group title |
Treatment (overall period)
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Reporting group description |
- | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
GA101
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Reporting group description |
Patients receive 4 cycles of GA-DHAP every 21 days and patients at least in stable disease after induction are transplanted. After ASCT, patients at least in stable disease receive a maintenance : Obinutuzumab every 2 months for 3 years. The patients with an informative MRD at baseline will continue with 3 additional years of maintenance in wich the patients will receive Obinutuzumab according to their MRD status. | ||
Subject analysis set title |
Efficacy set
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Subject analysis set type |
Full analysis | ||
Subject analysis set description |
The Efficacy set included all patients having signed the informed consent, received at least one dose of the IMP study drug (Obinutuzumab) and with an informative MRD in BM and/or blood at baseline.
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Subject analysis set title |
Modified Efficacy set
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Subject analysis set type |
Modified intention-to-treat | ||
Subject analysis set description |
The modified Efficacy Set included all patients having signed the informed consent, received at least one dose of the IMP study drug (Obinutuzumab), with an informative MRD in BM and/or blood at baseline and an informative MRD in BM after the 4 cycles of GA-DHAP or at treatment discontinuation.
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End point title |
MRD negativity (Q-PCR) [1] | |||||||||||||||
End point description |
MRD negativity rate on Bone Marrow after induction or at treatment discontinuation.
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End point type |
Primary
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End point timeframe |
End of induction
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| 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: The Lyma101 trial was designed in order to detect an increase of 15% of the MRD negativity in bone marrow (BM) rate for patients treated with GA-DHAP, assuming a 80% power at a 5% (1-sided) significance level using a single-stage phase II design. Experimental treatment will be considered ineffective if the MRD negativity proportion is ≤ 55% (P0) and effective if the MRD negativity proportion ≥ 70% (P1). |
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| No statistical analyses for this end point | ||||||||||||||||
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End point title |
PFS | ||||||||
End point description |
The Median-PFS was not reached at the end of study.
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End point type |
Secondary
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End point timeframe |
Since inclusion
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Attachments |
Untitled (Filename: Lyma101 - PFS.jpg) |
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| No statistical analyses for this end point | |||||||||
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End point title |
OS | ||||||||
End point description |
The Median-OS was not reached at the end of study.
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End point type |
Secondary
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End point timeframe |
Since inclusion
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Attachments |
Untitled (Filename: Lyma101 - OS.jpg) |
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| No statistical analyses for this end point | |||||||||
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End point title |
Overall Response rate | ||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
End of Treatment
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| No statistical analyses for this end point | |||||||||
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Adverse events information
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Timeframe for reporting adverse events |
All AEs of grade 3-5 for toxicities regardless relationship to investigational product occurring from the date of informed consent signature to 28 day after the last study drug administration of the study will be recorded.
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
25.0
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Reporting groups
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Reporting group title |
Safety set
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Reporting group description |
The Safety set will include all patients having signed the informed consent and received at least one dose of the IMP study drug (Obinutuzumab). | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 0% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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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20 Oct 2016 |
Protocol v2.0 : Capacity to replace Melphalan by cyclophosphamide |
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27 Feb 2017 |
Protocol v3.0 :
- national recommendation to avoid BEAC = suppression of the capacity to use cyclophosphamide instead of Melphalan
- recomemndation to treat with COP in case of High risk |
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14 Feb 2018 |
Protocol v4.0 :
Bendamustine to replace BCNU
Safety declaration rules
Secondary Statistics anaysis |
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17 Apr 2018 |
Protocol v5.0 :
Suspension of DHAOx
Prohibition of oxaliplatine
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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 | |||
