A Phase 1 interventional study of Obinutuzumab and Venetoclax in Follicular Lymphoma, sponsored by Swiss Group for Clinical Cancer Research. Completed at 6 sites in Switzerland. Open to participants aged 18 Years to 80 Years. Per ClinicalTrials.gov, last updated 2022-06-10.
Sponsored by Swiss Group for Clinical Cancer Research · Phase 1, Interventional, and Treatment
Follicular lymphoma (FL) is an indolent yet incurable lymphoma characterized by initial responses to standard therapies, invariably followed by shorter disease free intervals. Obinutuzumab, a novel type II, anti-CD20 monoclonal antibody has been approved in combination with chlorambucil for the treatment of previously untreated chronic lymphocytic leukemia (CLL) and in combination with bendamustine followed by obinutuzumab alone for FL who did not respond to, or who progressed during or after treatment with rituximab or a rituximab-containing regimen, or in relapse after such treatment. Additionally, venetoclax, a small molecule Bcl-2 inhibitor, showed single agent activity in relapsed/refractory (R/R) CLL and other B-cell lymphomas, including R/R FL. Preclinical evidence suggests a synergism of the two drugs in vitro as well as in different lymphoma in vivo models. Based on single agent clinical activity and on the preclinical data of the combination of both drugs and aiming to develop a new chemotherapy-free combination regimen, this trial plans to evaluate the combination of obinutuzumab and venetoclax in previously untreated FL patients in need of systemic therapy. This phase I study will provide information on the safety and tolerability together with evidence of preliminary antitumor activity. Combination treatment consists of a 6 cycles of 28 days each. The combination therapy is followed by a 2 years maintenance with obinutuzumab. Dosing of obinutuzumab is as per Swissmedic approval in FL.Venetoclax will be administered in different dose levels according to the trial design.
Follicular lymphoma is an indolent yet incurable lymphoma characterized by a relapsing-remitting course with initial responses to standard therapies, invariably followed by shorter disease free intervals. In recent years, significant treatment improvements have been achieved, mainly due to the introduction of the anti-CD20 monoclonal antibody rituximab in standard therapies. Unfortunately, most patients invariably relapse and require additional treatment. Therefore new therapies are needed in order to further improve treatment outcomes.
Recent advances in preclinical research and the improved knowledge of the molecular biology of lymphomas have permitted the development of a high number of new therapeutic compounds that inhibit components of altered signaling pathways that drive the genesis of lymphomas and their progression. Additionally, improvements in monoclonal antibody technology have permitted the development of new and active monoclonal antibodies that recognize different antigens on the surface of the lymphoma cells.
Obinutuzumab, a type II, anti-CD20 monoclonal antibody has been clinically tested both as single agent as well as in combination with chemotherapy or targeted agents, showing significant clinical activity in CLL and in FL patients that were refractory to rituximab.
Additionally venetoclax, a small molecule Bcl-2 inhibitor has recently advanced into clinical trials, showing a good safety profile and signs of single agent activity in CLL and other B-cell lymphomas, including patients with relapsed/refractory FL. There is interest to further investigate venetoclax in FL, given that the pathogenesis of this lymphoma relies on the chromosomal translocation t(14;18)(q32;q21), which is present in nearly all cases and results in constitutive overexpression of the BCL2 gene, allowing B cells to abrogate the default germinal center apoptotic program.
The combination of these two compounds is interesting given their single agent activity observed in FL. Preclinical studies have demonstrated a synergism both in vitro as well as in vivo models in different lymphomas and the two compounds are currently investigated in combination studies in CLL and with the chemotherapy CHOP regimen in non-Hodgkin lymphomas.
Based on the single agent activity of the two compounds and aiming to develop a new chemotherapy-free combination regimen, this SAKK trial plans to evaluate the combination of obinutuzumab and venetoclax in previously untreated FL patients in need of systemic therapy. There are data with venetoclax in combination with rituximab and bendamustine in relapsed or refractory Non-Hodgkin lymphoma (NHL) patients. No significant safety signal has been observed.
In the indication CLL the combination of obinutuzumab and venetoclax is currently investigated in a phase I dose finding trial (NCT01685892). In the currently ongoing CLL 14 trial the combination of obinutuzumab plus venetoclax is randomly compared to obinutuzumab plus chlorambucil within a prospective phase III study. Nevertheless, to the best of our knowledge, the proposed trial is one of the first trials worldwide investigating the combination treatment of obinutuzumab with venetoclax in FL as first line treatment. Given the need to further improve chemotherapy-free approaches in the first-line treatment of patients with FL in need of systemic therapy, this combination may provide an opportunity for an active and well tolerated regimen that does not present the short and long term toxicities of chemotherapy.
This phase I study will provide information on the safety and tolerability together with evidence of preliminary antitumor activity of obinutuzumab in combination with venetoclax in the first line treatment of FL.
5,578 studies on the registry are indexed under Lymphoma; 825 are open to participants now.
This study's enrollment of 25 is below the median of 40 across 4,508 interventional studies indexed under Lymphoma.
Browse Lymphoma studies →Swiss Group for Clinical Cancer Research is the lead sponsor of 107 studies on the registry; none are open to participants now.
Counted across the registry records on this site, refreshed daily.
Exclusion Criteria:
Known history of
Patients with a history of recurring or chronic infections may be included in the study but caution should be exercised and an infectious disease expert should be consulted before enrollment in the trial.
Coagulation parameters
Part A: dose escalation: Combination therapy N= 4-18 pts Cycle 1-6 (1 cycle = 28 days) Obinutuzumab: 1000 mg, i.v. infusion; d1, 8, 15 C1 and d1 C2-6 Venetoclax: p.o. once daily according to dose level (DL) Part B - dose expansion: Combination therapy N= up to 25 pts Cycle 1-6 (1 cycle = 28 days) Obinutuzumab: 1000 mg, i.v. infusion d1, 8, 15 C1 and d1 C2-6 Venetoclax: p.o. once daily according to MTD Part A and part B are followed (in case of no PD) by an obinutuzumab maintenance therapy for 2 years
Drug: Obinutuzumab · Drug: Venetoclax
Obinutuzumab: 1000 mg, i.v. infusion; d1, 8, 15 C1 and d1 C2-6
Also known as: GA101, Gazyvaro, Gazyva
p.o. once daily according to dose level (DL) or MTD
Also known as: ABT-199, GDC-0199, Venclexta
Dose limiting toxicities (DLT) during the first cycle
The primary endpoint is the frequency of DLTs which are relevant for the determination of the maximum tolerated dose (MTD) in the dose escalation phase of the trial.
Time frame: Day 28 of the first cycle
Adverse events (AEs)
Time frame: at 6 months (combination therapy) and at 2 years (maintenance therapy)
Laboratory safety variables
Time frame: at 6 months (combination therapy) and at 2 years (maintenance therapy)
Complete response (CR)
Time frame: at 6 months and 30 months
Overall response (OR) based on best response observed during combination therapy.
Time frame: at 6 months, based on best response observed during combination therapy, at 30 months and based on best response observed during whole therapy (combination and maintenance)
Duration of response
Time frame: at 2.5 years
Progression free survival (PFS)
Time frame: at 12 months, at 30 months
Plan to share: No
This study is completed, as verified in Jun 2022. You cannot join it, but the record below documents what was studied.
Get an email when the registry record changes — status, dates, results — or when someone posts here.
Sign in to followQuestions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.
Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.
Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.
Swiss Group for Clinical Cancer Research