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Mantle Cell LymphomaPhase 1/2OAsIsNCT02558816

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

A Phase 1/2 study testing Ibrutinib + GA101 +GDC-0199 in people with Mantle Cell Lymphoma, run by Nantes University Hospital at 9 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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). Read more about this study

Who is it for?
Ages 16 years and older
Conditions the study is for
Mantle Cell Lymphoma
What is being tested?
Ibrutinib + GA101 +GDC-0199
Could I receive a placebo?
No, everyone receives an active treatment
How many people
48 participants
Where
9 sitesin 2 countries
Study dates
14 Oct 2015to 13 May 2025
Phase
Phase 1/2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 16 years and older
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • 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:
Show all 38Show fewer
  • 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.
  • Women of childbearing potential must have a negative serum or urine pregnancy test at Screening. Women who are pregnant or breastfeeding are ineligible for this study.
  • Written signed informed consent form.
  • Non-Inclusion criteria :
  • Clinically significant cardiovascular disease such as uncontrolled or symptomatic arrhythmias, congestive heart failure, or myocardial infarction within 6 months of Screening, or any Class 3 (moderate) or Class 4 (severe) cardiac disease as defined by the New York Heart Association Functional Classification.
  • Major surgery within 4 weeks of inclusion.
  • Known central nervous system lymphoma.
  • History of stroke or intracranial haemorrhage within 6 months prior to inclusion.
  • Requires anticoagulation with warfarin or equivalent vitamin K antagonists (eg, phenprocoumon).
  • Impaired liver, renal (GFR<50ml/min) or other organ function which will interfere with the treatment.
  • Requires treatment with strong CYP3A inhibitors.
  • Vaccinated with live, attenuated vaccines within 6 months of inclusion.
  • Known history of human immunodeficiency virus (HIV) or active Hepatitis C Virus or active Hepatitis C Virus or active Hepatitis B Virus infection or any uncontrolled active systemic infection requiring intravenous (IV) antibiotics. (patients HbsAg+and/or antiHBc+ and/or HIV+ are excluded)
  • Any life-threatening illness, medical condition, or organ system dysfunction which, in the investigator's opinion, could compromise the subject's safety, interfere with the absorption or metabolism of study treatment (ibrutinib, GA101, GDC-0199) capsules, or put the study outcomes at undue risk.
  • Known hypersensitivity to study treatment (GA101, Ibrutinib, GDC-0199) or to any of the excipients.
  • Known allergy to xanthine oxidase inhibitors and rasburicase
  • Severe prior reactions to monoclonal antibodies or with prior significant toxicity (other than thrombocytopenia) from Bcl-2 inhibitor
  • History of prior other malignancy with the exception of: Curatively treated basal cell carcinoma or squamous cell carcinoma of the skin or carcinoma in situ of the cervix at any time prior to study
  • Other cancers not specified above which have been curatively treated and from which subject is disease-free for < 5 years .
  • Allografted patient
  • Psychiatric illness or condition which could interfere with their ability to understand the requirements of the study.
  • Pregnancy/lactation
  • Men or women of reproductive potential not agreeing to use acceptable method of birth control during treatment and for 18 months after completion of treatment for the women and 6 months for the men.
  • Use of any standard or experimental anti-cancer drug therapy within 28 days prior to the first dose of study drug.

Who cannot join

None listed.

Trial locations and contacts

9 sites in 2 countries.

9 sites in 2 countries

France7 sites

  • CHU Angers

    Angers, 49033

  • CHU de Dijon

    Dijon, 21000

  • Hôpital Claude Huriez - CHRU de Lille

    Lille, 59037

  • Hôpital Saint Eloi

    Montpellier, 34295

  • CHU de Nantes

    Nantes, 44093

  • Hôpital du Haut Lévêque

    Pessac, 33604

  • CHU Rennes

    Rennes, 35033

Other trials in France

United Kingdom2 sites

  • Derriford Hospital _ Plymouth Hospitals NHS Trust

    Plymouth, Devon, PL6 8DH

  • University of Southampton

    Southampton, SO16 6YD

Other trials in United Kingdom

About this study

Official title: A Phase I/II Trial of Obinutuzumab, ABT-199 (GDC-0199) Plus Ibrutinib in Relapsed / Refractory Mantle Cell Lymphoma Patients

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).

Read more

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.

Read the 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
Being tested
Ibrutinib + GA101 +GDC-0199
Medical subject headings
Lymphoma, Mantle-Cell

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Ibrutinib + GA101 +GDC-0199Drug

    Also called GA101 : Obinutuzumab, Ibrutinib, GDC-0199

    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

Study groups in NCT02558816
Study groupRoleWhat they receive
Ibrutinib - GA101 - GDC_0199ExperimentalSTEP 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
Receives: Drug: Ibrutinib + GA101 +GDC-0199

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: week 4

  2. 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

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

  3. 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

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

Secondary outcomes (6)

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

    Response (CR, PR, SD, PD) and overall response (CR+ PR) rates assessed by Cheson 99 and 07 criteria and Working Group Revised Response Criteria for Malignant Lymphomas 14

    Measured: 48 months

  2. Time to progression

    Measured: 48 months

  3. Overall survival

    Measured: 48 months

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

    Measured: 48 months

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

    Measured: 48 months

  6. Incidence and severity of tumor lysis syndrome

    Measured: 48 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted24 Sep 2015 (estimated)
  2. Study start14 Oct 2015
  3. Primary completionApr 2019
  4. Study completion13 May 2025

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
48 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02558816
Sponsor's protocol ID
RC14_0048
Other IDs
2014-003740-13, 2014
Acronym
OAsIs
Status last verified
Jul 2025
First submitted
27 Aug 2015
Last updated
14 Sep 2026
Results posted
No
Data monitoring committee
Yes

Publications

  • 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.

    PubMed 33181832

  • 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.

    PubMed 37562004

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Ibrutinib + GA101 +GDC-0199 in people with Mantle Cell Lymphoma, run by Nantes University Hospital at 9 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 38 inclusion and 0 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 14 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 9 sites in France, United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Step A : occurrence of unacceptable toxicity of the combination of GA101 and Ibrutinib during the first cycle of treatment (time frame: week 4). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02558816, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Sep 2026.

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