NCT02558816

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.

Trial Health

90
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
48

participants targeted

Target at P50-P75 for phase_1

Timeline
Completed

Started Oct 2015

Longer than P75 for phase_1

Geographic Reach
2 countries

9 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

August 27, 2015

Completed
28 days until next milestone

First Posted

Study publicly available on registry

September 24, 2015

Completed
20 days until next milestone

Study Start

First participant enrolled

October 14, 2015

Completed
3.5 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

April 1, 2019

Completed
6.1 years until next milestone

Study Completion

Last participant's last visit for all outcomes

May 13, 2025

Completed
Last Updated

July 24, 2025

Status Verified

July 1, 2025

Enrollment Period

3.5 years

First QC Date

August 27, 2015

Last Update Submit

July 21, 2025

Conditions

Mantle Cell Lymphoma

Outcome Measures

Primary Outcomes (3)

  • Step A : occurrence of unacceptable toxicity of the combination of GA101 and Ibrutinib during the first cycle of treatment

    4 weeks after initiation of treatment.

    week 4

  • Step B : occurrence of unacceptable toxicity (definition p3) of the combination of GA101 and Ibrutinib plus GDC-0199 during the cycle 2 in terms of Dose-Limiting Toxicities (DLTs)

    No unacceptable toxicity has been observed during step A, thefore the second step (step B) was initiated

    At the end of cycle 2 (each cycle is 28 days)

  • Step C : occurrence of unacceptable toxicity of the combination of GA101 and Ibrutinib and GDC-0199 at the end of the cycle 2

    The third step started, because no unacceptable toxicity has been observed during the second step

    At the end of cycle 2 (each cycle is 28 days)

Secondary Outcomes (6)

  • Response (CR, PR, SD, PD) and overall response (CR+ PR) rates

    48 months

  • Time to progression

    48 months

  • Overall survival

    48 months

  • Safety measured by type, frequency, severity of related treatment adverse event as Assessed by CTCAE v4.0.

    48 months

  • Incidence of Serious Adverse Event (SAE), Adverse Event (AE) and laboratory abnormalities.

    48 months

  • +1 more secondary outcomes

Study Arms (1)

Ibrutinib - GA101 - GDC_0199

EXPERIMENTAL

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

Drug: Ibrutinib + GA101 +GDC-0199

Interventions

Ibrutinib + GA101 +GDC-0199DRUG

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

Also known as: GA101 : Obinutuzumab, Ibrutinib, GDC-0199
Ibrutinib - GA101 - GDC_0199

Eligibility Criteria

Age16 Years+
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

  • Age ≥18 for French patients and Age ≥16 for UK patients
  • Step A + B : Relapsed / refractory MCL after at least one line of treatment. The relapse diagnosis (within 3 months before baseline), needs to be histologically confirmed (tumor biopsy or bone marrow biopsy) or confirmed by the presence (immunuphenotype) of circulating tumor cells on peripheral blood and/or bone marrow aspirate.
  • Step C : Untreated patients with histologically confirmed MCL (within 3 months before baseline). The initial diagnosis has to be confirmed according to WHO classification.
  • Stage II-IV in need of treatment
  • ECOG performance status of 0 - 2.
  • Haematology values must be within the following limits:
  • Absolute neutrophil count (ANC)≥ 1000/mm3 independent of growth factor support
  • Platelets ≥75,000/mm3 or ≥ 50,000/mm3 if bone marrow involvement and independent of transfusion support in either situation
  • Biochemical values within the following limits:
  • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3 x upper limit of normal (ULN)
  • Total bilirubin ≤ 1.5 x ULN unless bilirubin rise is due to Gilbert's syndrome or of non-hepatic origin
  • Serum creatinine ≤ 2 x ULN or estimated Glomerular Filtration Rate (Cockroft Gault 11) ≥ 50 mL/min/1.73m2
  • HIV, anti-HBc, HbsAg test negative
  • Life expectancy of more than 3 months.
  • Women of childbearing potential and men who are sexually active must be practicing a highly effective method of birth control during and after the study consistent with local regulations regarding the use of birth control methods for subjects participating in clinical trials. Men must agree to not donate sperm during and after the study. For females, these restrictions apply for at least 30 days after the last dose of venetoclax or 18 months after the last dose of obinutuzumab, whichever is longer. For males, these restrictions apply for 6 months after the last dose of study drug.
  • +19 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (9)

CHU Angers

Angers, 49033, France

Location

CHU de Dijon

Dijon, 21000, France

Location

Hôpital Claude Huriez - CHRU de Lille

Lille, 59037, France

Location

Hôpital Saint Eloi

Montpellier, 34295, France

Location

CHU de Nantes

Nantes, 44093, France

Location

Hôpital du Haut Lévêque

Pessac, 33604, France

Location

CHU Rennes

Rennes, 35033, France

Location

Derriford Hospital _ Plymouth Hospitals NHS Trust

Plymouth, Devon, PL6 8DH, United Kingdom

Location

University of Southampton

Southampton, SO16 6YD, United Kingdom

Location

Related Publications (2)

  • 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.

    PMID: 37562004DERIVED

  • 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.

    PMID: 33181832DERIVED

MeSH Terms

Conditions

Lymphoma, Mantle-Cell

Interventions

ibrutinibobinutuzumabvenetoclax

Condition Hierarchy (Ancestors)

Lymphoma, Non-HodgkinLymphomaNeoplasms by Histologic TypeNeoplasmsLymphoproliferative DisordersLymphatic DiseasesHemic and Lymphatic DiseasesImmunoproliferative DisordersImmune System Diseases

Study Officials

  • Steven LE GOUILL, Pr

    Nantes University Hospital

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

August 27, 2015

First Posted

September 24, 2015

Study Start

October 14, 2015

Primary Completion

April 1, 2019

Study Completion

May 13, 2025

Last Updated

July 24, 2025

Record last verified: 2025-07

Data Sharing

IPD Sharing
Will not share

Locations

FR(7)GB(2)