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A phase I/II trial of Obinutuzumab, ABT-199 (GDC-0199) plus Ibrutinib in Relapsed / Refractory Mantle Cell Lymphoma patients (OAsIs)
EU CTIS ID: 2024-516750-21-00
What this study is testing
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). 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) Step C : This step will be conducted if no unacceptable toxicity is 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.
- Phase I and Phase II (Integrated)- Other
A plain-language read of the study's public EU CTIS listing. The study team confirms the details.
Who can take part
You may be able to join if
- • Age ≥18 for French patients, Age ≥16 for English patients
- • 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.
- • Step A and B : Relapsed / refractory disease 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 mantle cell lymphoma (within 3 months before baseline). The initial diagnosis has to be confirmed according to WHO classification.
You likely can't join if
- • 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.
- • 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 ibrutinib 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
See the full eligibility criteria
- • Age ≥18 for French patients, Age ≥16 for English patients
- • 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.
- • Step A and B : Relapsed / refractory disease 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 mantle cell lymphoma (within 3 months before baseline). The initial diagnosis has to be confirmed according to WHO classification.
- • Stage II-IV in need of treatment (see Appendix 12 : Ann Arbor Staging)
- • ECOG performance status of 0 – 2
- • Hematology values must be within the following limits: a. Absolute neutrophil count (ANC) ≥1000/mm3 independent of growth factor support b. 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: a. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3 x upper limit of normal (ULN) b. Total bilirubin ≤ 1.5 x ULN unless bilirubin rise is due to Gilbert’s syndrome or of non-hepatic origin c. Serum creatinine ≤ 2 x ULN or estimated Glomerular Filtration Rate (Cockroft Gault11) ≥ 50 mL/min/1.73m2
- • HIV, anti-HBc, HbsAg test negative
- • Life expectancy of more than 3 months.
- • 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.
- • 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 ibrutinib 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 patients
- • 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
- • Major surgery within 4 weeks of inclusion
- • Use of any standard or experimental anti-cancer drug therapy within 28 days prior to the first dose of study drug
- • Known central nervous system lymphoma
- • History of stroke or intracranial hemorrhage 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 4 weeks of inclusion
- • Known history of human immunodeficiency virus (HIV) 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)
The study team makes the final eligibility decision.
Where it's taking place
- United Kingdom
Questions & answers
Do participants get paid in this trial?
This listing doesn't specify compensation. Many trials still reimburse travel or offer a stipend, so it's worth asking the study team when you connect.
Is it free to join, and do I need insurance?
Searching and applying through BridgeMD is free. In clinical trials the study-related treatment and visits are generally provided at no cost to you. You usually don't need insurance to take part - confirm specifics with the study team.
How long does this study last?
The listing doesn't state an exact length. The study team walks you through the schedule and number of visits before you decide to enroll.
Who can join this trial?
This study is enrolling all sexes, 18-64 years, 65+ years. The study team makes the final eligibility decision.
Where is this trial taking place?
Study sites include United Kingdom. Enter your location above to see the nearest site and check your eligibility.
Explore other conditions
BridgeMD is an information and trial-matching tool - not medical advice, and not the study sponsor. Details come from EU CTIS; the study team decides eligibility.