Ignite Creation Date:
2025-12-26 @ 11:48 AM
Ignite Modification Date:
2026-02-25 @ 8:58 PM
Study NCT ID:
NCT02558816
Status:
COMPLETED
Last Update Posted:
2025-07-24
First Post:
2015-08-27
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
A Trial of Obinutuzumab,GDC-0199 Plus Ibrutinib in Relapsed/Refractory Mantle Cell Lymphoma Patients
Sponsor:
Nantes University Hospital
Organization:
Study Overview
Official Title:
A Phase I/II Trial of Obinutuzumab, ABT-199 (GDC-0199) Plus Ibrutinib in Relapsed / Refractory Mantle Cell Lymphoma Patients
Status:
COMPLETED
Status Verified Date:
2025-07
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
OAsIs
Brief Summary:
This is an open label, multicenter, fixed dose and dose escalation, phase I/II study.
The study will be conducted in 3 steps. The first one (step A) will be to ensure the safety of the combination of Obinutuzumab (GA101) and Ibrutinib at fixed doses in patients with relapsed or refractory Mantle Cell Lymphoma (MCL).
A total of 9 patients have been included in the first step with grouped inclusions of three patients (safety evaluation performed at each inclusion of 3 patients).
No unacceptable toxicity has been observed during step A, thefore the second step (step B) was initiated. The aim of the second step was to determine the MTD of the GDC-0199 (400-600-800mg/d) in combination of GA101 and Ibrutinib (both respecting the previous doses) by using a Continual Reassessment Method. This dose escalation method was used until the 12th patient (3 patients included at 400mg/d of GDC-0199-(no DLT), 3 at 600mg/d- (no DLT) and 6 at 800mg/d, (not DLT reported so far). Once the last patient of the 800mg cohort is evaluated for DLT, all other patients will be treated at the dose of 400mg/d of GDC-0199.
The third step (step C) for untreated patients will be conducted at the dose of 400mg/d of GDC-0199. The aim of step C is to confirm the safety profile of the GA101 + Ibrutininb + GDC-199 combination according to step B result. 15 patients will be included in this step.
The study will be conducted in 3 steps. The first one (step A) will be to ensure the safety of the combination of Obinutuzumab (GA101) and Ibrutinib at fixed doses in patients with relapsed or refractory Mantle Cell Lymphoma (MCL).
A total of 9 patients have been included in the first step with grouped inclusions of three patients (safety evaluation performed at each inclusion of 3 patients).
No unacceptable toxicity has been observed during step A, thefore the second step (step B) was initiated. The aim of the second step was to determine the MTD of the GDC-0199 (400-600-800mg/d) in combination of GA101 and Ibrutinib (both respecting the previous doses) by using a Continual Reassessment Method. This dose escalation method was used until the 12th patient (3 patients included at 400mg/d of GDC-0199-(no DLT), 3 at 600mg/d- (no DLT) and 6 at 800mg/d, (not DLT reported so far). Once the last patient of the 800mg cohort is evaluated for DLT, all other patients will be treated at the dose of 400mg/d of GDC-0199.
The third step (step C) for untreated patients will be conducted at the dose of 400mg/d of GDC-0199. The aim of step C is to confirm the safety profile of the GA101 + Ibrutininb + GDC-199 combination according to step B result. 15 patients will be included in this step.
Detailed Description:
The study will be conducted into 3 steps for respecting the optimal safety of the OASIS trial:
Step A :
The primary objective of step A is to evaluate the safety of the combination of GA101 + Ibrutinib at fixed doses (560 mg per day of Ibrutinib + 1000 mg of GA101), in patients with relapsed or refractory Mantle Cell Lymphoma (MCL).
Secondary objectives:
* To describe the efficacy of the combination of GA101 and Ibrutinib in terms of clinical benefits response (overall response rate, complete response rate, partial response rate Cheson 99 and 07 criteria and Working Group Revised Response Criteria for Malignant Lymphomas 14), overall survival, progression free survival.
* To describe the safety and tolerability of the combination of GA101 and Ibrutinib
* To establish a bio-bank to explore biomarkers and mechanisms of action including resistance
Step B : Step B started because no unacceptable toxicity occurred in patients included in the step A.
The primary objective of this step is to determine the maximal tolerated dose (MTD) of the GDC-0199 in addition to the GA101 and Ibrutinib in relapsed refractory MCL patients by using a Continual Reassessment Method (CRM), used up to the 12th enrolled patients. No DLT occured for the first 12 patients. Based on the most recent publications, the dose of 400mg/d will be used from the 13th to the 24th patients (no CRM used).
Secondary objectives:
* To describe the efficacy of the combination GA101, Ibrutinib and GDC-0199 in terms of clinical benefits response (overall response rate, complete response rate, partial response rate Cheson 99 and 07 criteria and Working Group Revised Response Criteria for Malignant Lymphomas 14), overall survival, progression-free survival.
* To describe the safety and tolerability of the novel combination of GDC-0199, GA101 and Ibrutinib
* To establish a bio-bank to explore biomarkers and mechanism of action including resistance
Step C :
This step has started because no unacceptable toxicity was observed during the second step.
The primary objective of this step is to confirm the safety of the combination of GA101 + Ibrutinib + GDC-199 at fixed doses (560 mg per day of Ibrutinib + 1000 mg of GA101, 400mg/d of GDC-199 ), in patients with untreated Mantle Cell Lymphoma (MCL), at end of Cycle 2.
Secondary objectives :
* To describe the efficacy of the combination GA101, Ibrutinib and GDC-0199 in terms of clinical benefits response (overall response rate, complete response rate, partial response rate cheson 99 and 07 criteria and Working Group Revised Response Criteria for Malignant Lymphomas 14), overall survival, progression-free survival.
* To describe the safety and tolerability of the novel combination of GDC-0199, GA101 and Ibrutinib
* To establish a bio-bank to explore biomarkers and mechanism of action including resistance
Step A :
The primary objective of step A is to evaluate the safety of the combination of GA101 + Ibrutinib at fixed doses (560 mg per day of Ibrutinib + 1000 mg of GA101), in patients with relapsed or refractory Mantle Cell Lymphoma (MCL).
Secondary objectives:
* To describe the efficacy of the combination of GA101 and Ibrutinib in terms of clinical benefits response (overall response rate, complete response rate, partial response rate Cheson 99 and 07 criteria and Working Group Revised Response Criteria for Malignant Lymphomas 14), overall survival, progression free survival.
* To describe the safety and tolerability of the combination of GA101 and Ibrutinib
* To establish a bio-bank to explore biomarkers and mechanisms of action including resistance
Step B : Step B started because no unacceptable toxicity occurred in patients included in the step A.
The primary objective of this step is to determine the maximal tolerated dose (MTD) of the GDC-0199 in addition to the GA101 and Ibrutinib in relapsed refractory MCL patients by using a Continual Reassessment Method (CRM), used up to the 12th enrolled patients. No DLT occured for the first 12 patients. Based on the most recent publications, the dose of 400mg/d will be used from the 13th to the 24th patients (no CRM used).
Secondary objectives:
* To describe the efficacy of the combination GA101, Ibrutinib and GDC-0199 in terms of clinical benefits response (overall response rate, complete response rate, partial response rate Cheson 99 and 07 criteria and Working Group Revised Response Criteria for Malignant Lymphomas 14), overall survival, progression-free survival.
* To describe the safety and tolerability of the novel combination of GDC-0199, GA101 and Ibrutinib
* To establish a bio-bank to explore biomarkers and mechanism of action including resistance
Step C :
This step has started because no unacceptable toxicity was observed during the second step.
The primary objective of this step is to confirm the safety of the combination of GA101 + Ibrutinib + GDC-199 at fixed doses (560 mg per day of Ibrutinib + 1000 mg of GA101, 400mg/d of GDC-199 ), in patients with untreated Mantle Cell Lymphoma (MCL), at end of Cycle 2.
Secondary objectives :
* To describe the efficacy of the combination GA101, Ibrutinib and GDC-0199 in terms of clinical benefits response (overall response rate, complete response rate, partial response rate cheson 99 and 07 criteria and Working Group Revised Response Criteria for Malignant Lymphomas 14), overall survival, progression-free survival.
* To describe the safety and tolerability of the novel combination of GDC-0199, GA101 and Ibrutinib
* To establish a bio-bank to explore biomarkers and mechanism of action including resistance
Study Oversight
Has Oversight DMC:
True
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
False
Is an FDA AA801 Violation?:
Secondary ID Infos
| Secondary ID | Type | Domain | Link | View |
|---|---|---|---|---|
| 2014-003740-13 | EUDRACT_NUMBER | None | View |