A Trial of Obinutuzumab,GDC-0199 Plus Ibrutinib in Relapsed/Refractory Mantle Cell Lymphoma Patients

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.

Timeline

Start

2015-10-14

Primary completion

2019-04

Completion

2025-05-13

Publications

• Decombis S, Bellanger C, Le Bris Y, Madiot C, Jardine J, Santos JC, Boulet D, Dousset C, Menard A, Kervoelen C, Douillard E, Moreau P, Minvielle S, Moreau-Aubry A, Tessoulin B, Roue G, Bidere N, Le Gouill S, Pellat-Deceunynck C, Chiron D. CARD11 gain of function upregulates BCL2A1 expression and promotes resistance to targeted therapies combination in B-cell lymphoma. Blood. 2023 Nov 2;142(18):1543-1555. doi: 10.1182/blood.2023020211.
• Le Gouill S, Morschhauser F, Chiron D, Bouabdallah K, Cartron G, Casasnovas O, Bodet-Milin C, Ragot S, Bossard C, Nadal N, Herbaux C, Tessoulin B, Tchernonog E, Rossi C, McCulloch R, Gastinne T, Callanan MB, Rule S. Ibrutinib, obinutuzumab, and venetoclax in relapsed and untreated patients with mantle cell lymphoma: a phase 1/2 trial. Blood. 2021 Feb 18;137(7):877-887. doi: 10.1182/blood.2020008727.

Drugs

Indications