Clinical trial NCT02558816: A Trial of Obinutuzumab,GDC-0199 Plus Ibrutinib in Relapsed/Refractory Mantle Cell Lymphoma Patients
Official title: A Phase I/II Trial of Obinutuzumab, ABT-199 (GDC-0199) Plus Ibrutinib in Relapsed / Refractory Mantle Cell Lymphoma Patients
Conditions: Mantle Cell Lymphoma
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.
Interventions:
description: Step A : 9 patients receive the combination of Ibrutinib + GA101 Step B : 24 patients receive the combination of Ibrutinib + GA101 + GDC-0199 Step C : 15 untreated patients receive the combination of Ibrutinib + GA101 + GDC-0199
name: Ibrutinib + GA101 +GDC-0199
other_name: GA101 : Obinutuzumab
GDC-0199
Ibrutinib
type: Drug
Study arms:
design_group_description: STEP A:C1:Ibrutinib 560mg D2-28;GA101 1000mg day 1/2,8,15;C2-6:Ibrutinib 560mg D 1-28;GA101 1000mg D1 / C7 (Maintenance phase)-C24:Ibrutinib 560mg D1-28 (until progression);GA101 1000mg D1 every 2cycles (from C8) STEP B:C1:Ibrutinib 560mg D2-28;GA101 1000mg D1/2,8,15 / C1bis : Ibrutinib 560mg day 1-28 ; GA101 1000mg D 1 ; GDC-0199 20mg/d at W1, 50mg/d at W2, 100mg at W3, 200 mg/d at W4 / C2-6:Ibrutinib 560mg D1-28;GA101 1000mg D1;GDC-0199:400mg/d W1 and 400, 600 or 800mg/d W2-3-4 + 400, 600 or 800 mg/d C3-C6 (patients 1-12).Patients 13-24:GDC-199 400mg/d / C7(Maintenance phase)-C23:Ibrutinib 560mg D1-28 (until progression);GA101 1000mg D1 every 2 cycles (from C8);GDC:400, 600 or 800 mg D1-28 (patient 1-12).Patients 13-24 : 400mg/d STEP C:C1-C1bis=Step B; C2-6:Ibrutinib 560mg D1-28;GA101 1000mg D1;GDC:400mg/d C7 (Maintenance phase)-C23 : Ibrutinib 560mg D1-28 (-->progression);GA101 1000mg D1/2 cycles (from C8);GDC-0199 400mg/d
design_group_title: Ibrutinib - GA101 - GDC_0199
design_group_type: Experimental
Sponsor: Nantes University Hospital
Collaborators: Roche Pharma AG
Janssen LP
Drug name mappings:
name: 伊布替尼
lang: CN
name: Ibrutinib
lang: EN
name: イブルチニブ
lang: JP
name: 维奈克拉
lang: CN
name: Venetoclax
lang: EN
name: ベネトクラクス
lang: JP
name: 奥妥珠单抗
lang: CN
name: Obinutuzumab
lang: EN
name: オビヌツズマブ（遺伝子組換え）
lang: JP