Obinutuzumab + Ibrutinib for Indolent Non-Hodgkin's Lymphomas
Recruiting in Palo Alto (17 mi)
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Waitlist Available
Sponsor: Sidney Kimmel Cancer Center at Thomas Jefferson University
No Placebo Group
Prior Safety Data
Breakthrough Therapy
Trial Summary
What is the purpose of this trial?This phase II trial studies how well obinutuzumab and ibrutinib work as front line therapy in treating patients with indolent non-Hodgkin's lymphoma. Monoclonal antibodies, such as obinutuzumab, may interfere with the ability of cancer cells to grow and spread. Ibrutinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving obinutuzumab and ibrutinib may work better in treating patients with non-Hodgkin's lymphomas.
Do I have to stop taking my current medications for the trial?
The trial protocol does not specify if you must stop taking your current medications. However, you cannot use warfarin, other vitamin K antagonists, or strong CYP3A inhibitors. You should also be off corticosteroids 2 weeks before starting the trial.
What data supports the idea that Obinutuzumab + Ibrutinib for Indolent Non-Hodgkin's Lymphomas is an effective treatment?
The available research does not provide specific data on the combination of Obinutuzumab and Ibrutinib for Indolent Non-Hodgkin's Lymphomas. However, it does mention that Ibrutinib, when combined with another drug called Rituximab, showed positive results in treating a similar condition called follicular lymphoma. In this study, a high percentage of patients responded well to the treatment, with many experiencing complete responses. This suggests that Ibrutinib can be effective in treating certain types of lymphomas, but there is no direct data on its combination with Obinutuzumab for Indolent Non-Hodgkin's Lymphomas in the provided information.
12345What safety data exists for the treatment of Obinutuzumab and Ibrutinib in indolent non-Hodgkin's lymphomas?
Existing safety data for Obinutuzumab and Ibrutinib in indolent non-Hodgkin's lymphomas includes findings from several studies. Obinutuzumab, when used in combination with bendamustine, showed a generally manageable tolerability profile with mild to moderate infusion-related reactions and neutropenia as common adverse events. In the GAUDI study, Obinutuzumab combined with chemotherapy (G-CHOP or G-FC) resulted in high response rates and an acceptable safety profile, with infusion-related reactions and neutropenia being the most common adverse events. Ibrutinib, when studied in combination with nivolumab, was assessed for safety in relapsed or refractory B-cell malignancies, indicating ongoing evaluation of its safety profile in combination therapies.
23678Is the drug combination of Obinutuzumab and Ibrutinib promising for treating indolent non-Hodgkin's lymphomas?
Yes, the drug combination of Obinutuzumab and Ibrutinib is promising for treating indolent non-Hodgkin's lymphomas. Obinutuzumab has shown to significantly extend the time patients live without the disease getting worse, especially in those who did not respond well to previous treatments. This makes it a valuable option for patients with this type of lymphoma.
236910Eligibility Criteria
This trial is for adults with untreated indolent non-Hodgkin's lymphoma, including various types of marginal zone and follicular lymphomas. Participants must have measurable disease, be able to swallow pills, and not have severe liver failure or other serious health conditions. Women of childbearing potential need a negative pregnancy test and agree to use effective contraception.Inclusion Criteria
I have symptoms or conditions due to my lymphoma that require treatment.
I have a type of slow-growing non-Hodgkin's lymphoma known as follicular lymphoma.
My MZL cancer requires systemic therapy and has been confirmed with a biopsy.
+28 more
Exclusion Criteria
I do not have active hepatitis B.
Patient is receiving other investigational drugs
I haven't had a major infection or been on IV antibiotics in the last 4 weeks.
+23 more
Participant Groups
The study tests the combination of obinutuzumab (a monoclonal antibody) and ibrutinib (an enzyme blocker) as initial treatment for patients with certain types of slow-growing non-Hodgkin's lymphoma. The goal is to see if this drug combo can stop cancer cells from growing by interfering with their function.
1Treatment groups
Experimental Treatment
Group I: Treatment (ibrutinib, obinutuzumab)Experimental Treatment3 Interventions
Patients receive ibrutinib orally (PO) once daily (QD) on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also receive obinutuzumab intravenously (IV) on days 1, 8, and 15 of cycle 1 and day 1 of subsequent cycles. Treatment repeats every 28 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Beginning 2 months after cycle 6, patients with stable disease will continue to receive obinutuzumab every 2 months for a total of 12 doses.
After completion of study treatment, patients are followed up monthly for 1 year, every 3-6 months for 4 years, and then annually for up to 2 years.
Ibrutinib is already approved in European Union, United States, Canada, Japan for the following indications:
🇪🇺 Approved in European Union as Imbruvica for:
- Chronic lymphocytic leukemia
- Mantle cell lymphoma
- Waldenström's macroglobulinemia
- Marginal zone lymphoma
- Graft-versus-host disease
🇺🇸 Approved in United States as Imbruvica for:
- Chronic lymphocytic leukemia/small lymphocytic lymphoma
- Mantle cell lymphoma
- Waldenström's macroglobulinemia
- Marginal zone lymphoma
- Graft-versus-host disease
🇨🇦 Approved in Canada as Imbruvica for:
- Chronic lymphocytic leukemia
- Mantle cell lymphoma
- Waldenström's macroglobulinemia
- Marginal zone lymphoma
🇯🇵 Approved in Japan as Imbruvica for:
- Chronic lymphocytic leukemia
- Mantle cell lymphoma
- Waldenström's macroglobulinemia
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Sidney Kimmel Cancer Center at Thomas Jefferson UniversityPhiladelphia, PA
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Who Is Running the Clinical Trial?
Sidney Kimmel Cancer Center at Thomas Jefferson UniversityLead Sponsor
Genentech, Inc.Industry Sponsor
Pharmacyclics LLC.Industry Sponsor
References
Ibrutinib (imbruvica): a novel targeted therapy for chronic lymphocytic leukemia. [2021]Ibrutinib (Imbruvica): a novel targeted therapy for chronic lymphocytic leukemia.
Battle of Thermopylae: 300 Spartans (natural killer cells plus obinutuzumab) versus the immortal warriors (chronic lymphocytic leukemia cells) of Xerxes' army. [2022]To analyze the effects of subcutaneous or intravenous rituximab + lymphokine-activated killer cells, obinutuzumab or ibrutinib on natural killer (NK) cell levels in chronic lymphocytic leukemia and follicular lymphoma patients.
Pharmaceutical approval update. [2021]Obinutuzumab (Gazyva) for chronic lymphocytic leukemia; ibrutinib (Imbruvica) for mantle-cell lymphoma; and sofosbuvir (Sovaldi) for chronic hepatitis C infection.
The combination of ibrutinib and rituximab demonstrates activity in first-line follicular lymphoma. [2021]This phase 2 study evaluated the activity and safety of ibrutinib, a Bruton's tyrosine kinase inhibitor, plus rituximab in adults with previously untreated follicular lymphoma. Patients received once-daily ibrutinib 560 mg continuously plus once-weekly rituximab 375 mg/m2 for 4 weeks beginning Week 1 (Arm 1, n = 60) or Week 9 (following an 8-week ibrutinib lead-in) to explore biomarkers (Arm 2, n = 20). The primary endpoint was the best overall response rate (ORR). The median age was 58 years; most had an Eastern Cooperative Oncology Group Performance Status of 0 (74%) and Stage III/IV disease (84%). At a median study follow-up of 34 months in Arm 1 and 29 months in Arm 2, ORRs were 85% [95% confidence interval (CI) 73-93] and 75% (95% CI 51-91), respectively, with complete responses in 40% and 50%. The median duration of response was not reached in either arm; 30-month progression-free and overall survival rates were 67% and 97% (Arm 1) and 65% and 100% (Arm 2). The most common adverse events were fatigue, diarrhoea and nausea. Higher grade (Grade 3/4) haematological, haemorrhagic and cardiac events occurred infrequently. Ibrutinib plus rituximab was active and tolerable in first-line follicular lymphoma.
Ibrutinib in Combination With Rituximab for Indolent Clinical Forms of Mantle Cell Lymphoma (IMCL-2015): A Multicenter, Open-Label, Single-Arm, Phase II Trial. [2022]The need for an individualized management of indolent clinical forms in mantle cell lymphoma (MCL) is increasingly recognized. We hypothesized that a tailored treatment with ibrutinib in combination with rituximab (IR) could obtain significant responses in these patients.
Obinutuzumab: A Review in Rituximab-Refractory or -Relapsed Follicular Lymphoma. [2018]Obinutuzumab (Gazyva®, Gazyvaro®) is a recombinant, monoclonal, humanized and glycoengineered, type II, anti-CD20, IgG1 antibody. It has recently been granted an additional indication for the treatment of patients with follicular lymphoma who relapsed after, or are refractory to, a rituximab-containing regimen. In the primary analysis of the large, phase III GADOLIN study, induction therapy with obinutuzumab plus bendamustine followed by obinutuzumab maintenance prolonged progression-free survival (PFS) to a statistically significant extent relative to induction with bendamustine monotherapy in patients with indolent non-Hodgkin's lymphoma (iNHL). The improvement in PFS was largely driven by the subgroup of patients with follicular lymphoma, who also had prolonged overall survival (OS) in a planned updated analysis. Obinutuzumab had a generally manageable tolerability profile in these patients; mild to moderate infusion-related reactions (IRRs) were the most common treatment-emergent adverse events (AEs) and neutropenia the most common grade 3 or 4 treatment-related AEs. Although additional studies and longer-term data are needed to further assess treatment benefits with obinutuzumab, current evidence indicates that obinutuzumab is a useful treatment option for patients with rituximab-refractory or -relapsed follicular lymphoma.
Obinutuzumab (GA101) plus CHOP or FC in relapsed/refractory follicular lymphoma: results of the GAUDI study (BO21000). [2022]The safety and activity of obinutuzumab (GA101) plus chemotherapy in relapsed/refractory follicular lymphoma was explored in 56 patients. Participants received obinutuzumab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (G-CHOP; every 3 weeks for 6 to 8 cycles) or obinutuzumab plus fludarabine and cyclophosphamide (G-FC; every 4 weeks for 4 to 6 cycles). Patients were randomly assigned to either obinutuzumab 1600 mg on days 1 and 8 of cycle 1 followed by 800 mg on day 1 of subsequent cycles or 400 mg for all doses. Treatment responders were eligible for obinutuzumab maintenance every 3 months for up to 2 years. Grade 1/2 infusion-related reactions (IRRs) were the most common treatment-related adverse event (AE) (all grades: G-CHOP, 68%; G-FC, 82%). Grade 3/4 IRRs were rare (7%) and restricted to the first infusion. All patients received the planned obinutuzumab dose. Neutropenia was the most common treatment-related hematologic AE for G-CHOP (43%) and G-FC (50%). At induction end, 96% (27/28) of patients receiving G-CHOP (complete response [CR], 39% [11/28]) and 93% (26/28) receiving G-FC (CR, 50% [14 of 28]) achieved responses. G-CHOP and G-FC had an acceptable safety profile with no new or unexpected AEs, but G-FC was associated with more AEs than G-CHOP. Obinutuzumab plus chemotherapy resulted in 93% to 96% response rates, supporting phase 3 investigation. This trial was registered at www.clinicaltrials.gov as #NCT00825149.
Safety and activity of ibrutinib in combination with nivolumab in patients with relapsed non-Hodgkin lymphoma or chronic lymphocytic leukaemia: a phase 1/2a study. [2021]Preclinical studies have shown synergistic antitumour effects between ibrutinib and immune-checkpoint blockade. The aim of this study was to assess the safety and activity of ibrutinib in combination with nivolumab in patients with relapsed or refractory B-cell malignant diseases.
Obinutuzumab plus bendamustine versus bendamustine monotherapy in patients with rituximab-refractory indolent non-Hodgkin lymphoma (GADOLIN): a randomised, controlled, open-label, multicentre, phase 3 trial. [2022]Patients with indolent non-Hodgkin lymphoma who fail to achieve adequate disease control with rituximab-based treatment have few treatment options and a poor prognosis. We aimed to assess a combination of obinutuzumab (GA101), a novel glyco-engineered type II anti-CD20 monoclonal antibody, and bendamustine in this patient population.
Obinutuzumab for the treatment of indolent lymphoma. [2018]Obinutuzumab is a humanized, type II anti-CD20 monoclonal antibody designed for strong induction of direct cell death and antibody-dependent cell-mediated cytotoxicity. The Phase III GADOLIN trial tested the clinical efficacy of obinutuzumab plus bendamustine followed by obinutuzumab monotherapy in rituximab-refractory indolent non-Hodgkin lymphoma versus treatment with bendamustine alone. It demonstrated significantly longer progression-free survival for the obinutuzumab-containing regimen in this difficult to treat patient group. Based on the results of this trial, US FDA approval was most recently granted for obinutuzumab in the treatment of follicular lymphoma that has relapsed after or was refractory to a rituximab-containing regimen. This article summarizes the available data on chemistry, pharmacokinetics, clinical efficacy and safety of obinutuzumab in the treatment of indolent non-Hodgkin lymphoma.