Clinical Trial Results:
Phase IIa study on the role of Gemcitabine plus Romidepsin (GEMRO regimen) in the treatment of relapsed/refractory peripheral T-cell lymphoma patients.
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Summary
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EudraCT number |
2012-001404-38 |
Trial protocol |
IT |
Global end of trial date |
02 Jul 2018
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Results information
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Results version number |
v1(current) |
This version publication date |
01 Apr 2022
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First version publication date |
01 Apr 2022
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Other versions |
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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 |
FIL_GEMRO
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT01822886 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Fondazione Italiana Linfomi (FIL) ONLUS
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Sponsor organisation address |
Piazza Turati 5, Alessandria, Italy,
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Public contact |
Segreteria, Fondazione Italiana Linfomi ONLUS, +39 0131/033151, segreteriadirezione@filinf.it
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Scientific contact |
Segreteria, Fondazione Italiana Linfomi ONLUS, +39 0131/033151, segreteriadirezione@filinf.it
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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 |
24 May 2019
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
15 Dec 2014
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Global end of trial reached? |
Yes
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Global end of trial date |
02 Jul 2018
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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, as assessed by the CR rate, of GEMRO combination as salvage treatment in PTCL.
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Protection of trial subjects |
Safety assessment by a safety committee will be performed after the first three patients have completed at least one cycle, after 6 patients have completed 2 cycles and quarterly thereafter. For hematologic or non-hematologic drug-related toxicity grade 3 or more the administration of the drug(s) will be postponed a maximum of 3 weeks until toxicity returns to < Grade 1.
In case of the following drug-related toxicities the dose of romidepsin will be modified:
- Grade 4 neutropenia and/or thrombocytopenia that last more than 7 days
- Grade 3 neutropenia and/or thrombocytopenia that last more than 14 days
- Grade 3 extra-hematological toxicity lasting for more than week, or Grade 4 extrahematological toxicity
- Grade 4 febrile neutropenia,
- Cardiac toxicity: QTc ≥ 501 msec, VT, including Torsade de Pointes, VF, new occurrence
of > Grade >2 atrial fibrillation or flutter
- Inability to initiate cycle 2, day 1 of therapy within 28 days of anticipated start.
If toxicity recurs, the dose will be further reduced.
Patients who experience toxicity may continue in the study. They may resume treatment at the indicated dose level below that at which the toxicity was observed once they have recovered from the event. Appropriate cardiovascular monitoring precautions will be considered, such as the monitoring of electrolytes and ECGs at baseline and every two cycle during treatment with romidepsin.
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Background therapy |
- | ||
Evidence for comparator |
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Actual start date of recruitment |
08 Jan 2013
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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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 |
Italy: 20
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Worldwide total number of subjects |
20
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EEA total number of subjects |
20
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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) |
15
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From 65 to 84 years |
5
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85 years and over |
0
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Recruitment
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Recruitment details |
Twenty patients recruited in Italy from 8 January 2013, with date of last completed at 15 December 2014 | ||||||||||||
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Pre-assignment
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Screening details |
The screening can be up to 28 days prior to first infusion. Bone marrow results obtained 56 day prior to first infusion will be allowed. All patients must satisfy all the inclusion criteria and none of exclusion criteria. | ||||||||||||
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Period 1
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Period 1 title |
Baseline (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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Single arm | ||||||||||||
Arm description |
The combination of romidepsin and gemcitabine will be evaluated at the following dose: Romidepsin 12 mg/m2 d.1,8, 15 + Gemcitabine 800 mg/m2 d.1, 15 for 6 cycles by 28 days followed by Romidepsin 14 mg/m2 d. 1, 15 to PD | ||||||||||||
Arm type |
Single arm study | ||||||||||||
Investigational medicinal product name |
Gemcitabine
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Concentrate for solution for infusion
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Routes of administration |
Infusion
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Dosage and administration details |
Gemcitabine 800 mg/m2 d.1, 15 for 6 cycles by 28 days
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Investigational medicinal product name |
Romidepsin
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Powder and solvent for solution for infusion
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Routes of administration |
Infusion
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Dosage and administration details |
Romidepsin 12 mg/m2 d.1,8, 15 for 6 cycles + Gemcitabine 800 mg/m2 d.1, 15 for 6 cycles by 28 days followed by Romidepsin 14 mg/m2 d. 1, 15 to PD
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Baseline characteristics reporting groups
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Reporting group title |
Baseline
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Reporting group description |
- | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Single arm
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Reporting group description |
The combination of romidepsin and gemcitabine will be evaluated at the following dose: Romidepsin 12 mg/m2 d.1,8, 15 + Gemcitabine 800 mg/m2 d.1, 15 for 6 cycles by 28 days followed by Romidepsin 14 mg/m2 d. 1, 15 to PD | ||
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End point title |
Complete Remission (CR) Rate [1] | ||||||
End point description |
The proportion of patients with complete remission (CR) according to the Revised Response Criteria for Malignant Lymphoma (Cheson et al. 2007)
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End point type |
Primary
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End point timeframe |
18 months
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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 study is single-arm without comparator. |
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| No statistical analyses for this end point | |||||||
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End point title |
Overall Response Rate (ORR) | ||||||
End point description |
The Overall Response Rate (ORR=CR+CRu+PR) is defined as the proportion of patients who achieve CR, CRu or PR relative to the per-protocol population. Disease response and progression will be evaluated according to the “Revised Response Criteria” for malignant lymphoma (Cheson et al. 2007)
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End point type |
Secondary
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End point timeframe |
24 months
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| No statistical analyses for this end point | |||||||
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End point title |
Progression Free Survival (PFS) | ||||||||
End point description |
Progression Free survival (PFS) is defined as the time from start of study treatment to first documentation of objective tumor progression or to death due to any cause, whichever comes first. PFS data will be censored on the day following the date of the last radiological assessment of measured lesions documenting absence of progressive disease for patients who do not have objective tumor progression and are still on study at the time of an analysis, are given antitumor treatment other than the study treatment or stem cell transplant, or are removed from study prior to documentation of objective tumor progression. Patients lacking an evaluation of tumor response after their first dose will have their event time censored at 1 day.
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End point type |
Secondary
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End point timeframe |
24 months
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| No statistical analyses for this end point | |||||||||
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End point title |
Overall Survival (OS) | ||||||||
End point description |
Overall Survival (OS) is measured from the date of study entry to the date of patient’s death. If the patient is alive or his vital status is unknown, the date of death will be censored at the date that the patient is last known to be alive. Time to subsequent anti-lymphoma therapy will be assessed, for all patients, from the initiation of study treatment to the start of alternative therapy. Patients who do not receive alternate therapy will be censored in the analysis at the date of death or the last known date alive.
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End point type |
Secondary
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End point timeframe |
24 months
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| No statistical analyses for this end point | |||||||||
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End point title |
Safety | ||||||||||||||
End point description |
Frequency of toxicities Grade 3 and 4.
Frequency of toxicities was reported by type and grade according to the National Cancer Institute Common Terminology Criteria for Adverse Events (version 4.0)
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End point type |
Secondary
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End point timeframe |
24 months
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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 |
24 months
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Adverse event reporting additional description |
Any Grade
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
NCI CTCAE | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
4
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Reporting groups
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Reporting group title |
Single arm
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Reporting group description |
The combination of romidepsin and gemcitabine will be evaluated at the following dose: Romidepsin 12 mg/m2 d.1,8, 15 + Gemcitabine 800 mg/m2 d.1, 15 for 6 cycles by 28 days followed by Romidepsin 14 mg/m2 d. 1, 15 to PD | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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? No | |||
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 | |||
Online references |
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| http://www.ncbi.nlm.nih.gov/pubmed/27071522 |
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