Neoplasms

Blood and Lymph Conditions

Immune System Diseases

All Conditions

Rare Diseases

Lymphoma

Lymphoma, Follicular

Neoplasms by Histologic Type

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Lymphoma, Non-Hodgkin

Lymphosarcoma

Follicular Lymphoma

All Drugs and Chemicals

Antineoplastic Agents

Amino Acids

Antibodies

Antibodies, Monoclonal

Venetoclax

Obinutuzumab

Immunoglobulins

Ibrutinib

Tyrosine Kinase Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Antineoplastic Agents, Immunological

Tyrosine

Patients receive obinutuzumab IV over 60 minutes on days 1, 8, and 15 of cycle 1, day 1 of cycles 2-6, 8, 10, 12, 14, 16, 18, 20, 22, and 24. Patients also receive venetoclax PO QD on days 1-28 (days 4-28 of cycle 1) and ibrutinib PO QD on days 1-28. Treatment repeats every 28 days for up to 24 cycles in the absence of disease progression or unacceptable toxicity.

Lizbeth Gasga

Haifaa Abdulhaq, MD

Shenetra Walker

John Timmerman, MD

Selina Laqui

Joseph M. Tuscano

Benjamin Heyman, MD

Joseph M Tuscano

This phase II trial studies how well obinutuzumab, ibrutinib, and venetoclax work in treating patients with previously untreated stage II-IV follicular lymphoma. Immunotherapy with obinutuzumab may induce changes in body's immune system and may interfere with the ability of tumor cells to grow and spread. Ibrutinib and venetoclax may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving obinutuzumab, ibrutinib, and venetoclax together may work better in treating follicular lymphoma compared to each drug alone.

PRIMARY OBJECTIVE:

I. To evaluate the efficacy of obinutuzumab combined with venetoclax and ibrutinib in patients with previously untreated follicular lymphoma (FL) (determined by a positron emission tomography \[PET\]/computed tomography \[CT\] complete response \[CR\] rate at 12 months as per International Workshop Lymphoma Response Criteria, Cheson 2014).

SECONDARY OBJECTIVES:

I. To evaluate the safety and tolerability of obinutuzumab in combination with venetoclax and ibrutinib in patients with untreated FL as assessed by frequency, severity, and relatedness of treatment-emergent adverse events (AEs) as well as frequency of treatment-emergent AEs requiring discontinuation or dose reduction of study drug.

II. To evaluate the efficacy of obinutuzumab in combination with venetoclax and ibrutinib in subjects with untreated FL as assessed by CR at 30 months, overall response rate (ORR) (CR + partial response \[PR\]), duration of response (DOR), time to next anti-lymphoma treatment (TTNT), progression-free survival (PFS), and OS.

OUTLINE:

Patients receive obinutuzumab intravenously (IV) over 60 minutes on days 1, 8, and 15 of cycle 1, day 1 of cycles 2-6, 8, 10, 12, 14, 16, 18, 20, 22, and 24. Patients also receive venetoclax orally (PO) once daily (QD) on days 1-28 (days 4-28 of cycle 1) and ibrutinib PO QD on days 1-28. Treatment repeats every 28 days for up to 24 cycles in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up periodically for up to 2 years.

Obinutuzumab, Ibrutinib, and Venetoclax for the Treatment of Previously Untreated Stage II-IV Follicular Lymphoma

A Phase II Trial of the Combination of Obinutuzumab, Ibrutinib, and Venetoclax in Patients With Previously Untreated Follicular Lymphoma

Determined by positron emission tomography (PET)/computed tomography (CT) based on Cheson, Lugano classification 2014 as assessed by the investigator. Logistic regression will be utilized to assess the effect of patient prognostic factors on the response rate.

Adverse events will be graded and recorded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Toxicity data by type and severity will be summarized by frequency tables.

Adverse events will be graded and recorded according to NCI CTCAE version 5.0. Toxicity data by type and severity will be summarized by frequency tables.

Determined by PET/CT based on Cheson, Lugano classification 2014 as assessed by the investigator. Logistic regression will be utilized to assess the effect of patient prognostic factors on the response rate. The number and percentage of subjects with a CR will be tabulated.

CR + partial response (PR), determined by PET/CT based on Cheson, Lugano classification 2014 as assessed by the investigator. Logistic regression will be utilized to assess the effect of patient prognostic factors on the response rate. The number and percentage of subjects with an ORR will be tabulated. The best ORR will be recorded.

CR + PR, determined by PET/CT based on Cheson, Lugano classification 2014 as assessed by the investigator. Kaplan-Meier methodology will be used to estimate event-free curves, median, and 95% confidence interval (CI).

Kaplan-Meier methodology will be used to estimate event-free curves, median, and 95% CI. Comparison by important subgroups will be made using the log-rank test.

National Cancer Institute (NCI)

Pharmacyclics LLC.

Genentech, Inc.

Joseph Tuscano

Principal Investigator

Lymphoma, B-Cell, Marginal Zone

Lymphoma, B-Cell

B-cell Lymphoma

Marginal Zone Lymphoma

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.

Laboratory Biomarker Analysis

Ubaldo Martinez-Outschoorn, MD

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.

PRIMARY OBJECTIVES:

I. To assess the efficacy of the combination of ibrutinib and obinutuzumab in chemotherapy naive patients with indolent lymphomas.

SECONDARY OBJECTIVES:

I. To assess progression free survival rates and overall survival rates in indolent lymphomas.

II. To assess safety and tolerability of the combination. III. To evaluate response using positron emission tomography (PET) and correlate PET negativity with durability of response.

OUTLINE:

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 1 year later.

Obinutuzumab and Ibrutinib as Front Line Therapy in Treating Patients With Indolent Non-Hodgkin's Lymphomas

Phase II, Single Arm, Open Label Multi-center Study of Obinutuzumab and Ibrutinib in the Front Line Treatment of Indolent Non-Hodgkin's Lymphomas

Response will be assessed by the revised Lugano. Will compute estimates of response, along with corresponding confidence intervals, using appropriate exact methods that take into account the 2-stage design.

Assessed using Common Terminology Criteria for Adverse Events version 5.0. Will compute estimates toxicity rates, along with corresponding confidence intervals, using appropriate exact methods that take into account the 2-stage design.

Sidney Kimmel Cancer Center at Thomas Jefferson University

Antirheumatic Agents

Rituximab

Lenalidomide

Immunoglobulins, Intravenous

Immunologic Factors

Angiogenesis Inhibitors

Growth Inhibitors

Patients receive lenalidomide PO on days 1-21, rituximab IV over 4-6 hours on days 1, 8, 15, and 22 of cycle 1 and day 1 of all subsequent cycles, and ibrutinib PO QD on days 1-28. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity.

Loretta J Nastoupil

This phase II trial studies how well ibrutinib in combination with rituximab and lenalidomide works in treating patients with previously untreated, stage II-IV follicular lymphoma or marginal zone lymphoma. Ibrutinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies, such as rituximab, may block cancer growth in different ways by targeting certain cells. Biological therapies, such as lenalidomide, use substances made from living organisms that may stimulate or suppress the immune system in different ways and stop cancer cells from growing. Giving ibrutinib in combination with rituximab and lenalidomide may work better in treating follicular lymphoma or marginal zone lymphoma.

PRIMARY OBJECTIVES:

I. To evaluate the efficacy of ibrutinib combined with rituximab and lenalidomide in patients with previously untreated follicular lymphoma (FL) and marginal zone lymphoma (determined by progression-free survival at 2 years).

SECONDARY OBJECTIVES:

I. To evaluate the efficacy of ibrutinib combined with rituximab and lenalidomide in subjects with FL as assessed by complete response rate (CR) at 120 weeks, overall response rate (ORR), duration of response (DOR), event free survival (EFS), time to next anti-lymphoma treatment (TTNT), and overall survival (OS).

II. To evaluate the safety and tolerability of ibrutinib combined with rituximab and lenalidomide in previously untreated subjects with FL and marginal zone lymphoma.

EXPLORATORY OBJECTIVES:

I. To evaluate prognostic and mechanistic biomarkers relative to treatment outcomes.

OUTLINE:

Patients receive lenalidomide orally (PO) on days 1-21, rituximab intravenously (IV) over 4-6 hours on days 1, 8, 15, and 22 of cycle 1 and day 1 of all subsequent cycles, and ibrutinib PO once daily (QD) on days 1-28. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 12 weeks for 1 year and then every 24 weeks for 2 years.

Ibrutinib in Combination With Rituximab and Lenalidomide in Treating Patients With Previously Untreated, Stage II-IV Follicular Lymphoma or Marginal Zone Lymphoma

An Open Label, Phase 2 Study of Ibrutinib in Combination With Rituximab and Lenalidomide in Previously Untreated Subjects With Follicular Lymphoma and Marginal Zone Lymphoma

Response will be assessed by the investigator based on the 2014 Cheson Lugano criteria. The 2-year PFS rate will be calculated and corresponding 95% confidence interval (CI) will be derived. Kaplan-Meier method will be used to estimate the PFS. Corresponding 95% CI will be summarized. Cox proportional hazards models will be used to assess the effects of patient prognostic factors on time-to-event endpoints.

Will be defined as the percentage of subjects with a CR at 120 weeks as determined by the principal investigator (Cheson, Lugano classification 2014).

Will be defined as the percentage of subjects with an ORR and assessed by the investigator based on Cheson, Lugano 2014. The best ORR will be recorded.

Kaplan-Meier methodology will be used to estimate event-free curves, median, and 95% CI.

Additional AE summaries will include AE frequency by AE severity and by relationship to study drug.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Obinutuzumab, Ibrutinib, and Venetoclax for the Treatment of Previously Untreated Stage II-IV Follicular Lymphoma	NCT04450173	Ann Arbor Stage... Ann Arbor Stage... Ann Arbor Stage... Grade 1 Follicu... Grade 2 Follicu... Grade 3a Follic...	Ibrutinib Obinutuzumab Venetoclax	18 Years -	University of California, Davis
Obinutuzumab and Ibrutinib as Front Line Therapy in Treating Patients With Indolent Non-Hodgkin's Lymphomas	NCT03198026	Non-Hodgkin's L... Ann Arbor Stage... Ann Arbor Stage... Ann Arbor Stage... Ann Abor Stage ... Ann Arbor Stage... Ann Arbor Stage... Ann Arbor Stage... Ann Arbor Stage... Ann Arbor Stage... Ann Arbor Stage... Ann Arbor Stage... Grade 1 Follicu... Grade 2 Follicu... Grade 3a Follic... Indolent Non-ho... Stage II Spleni... Stage III Splen... Stage IV Spleni...	Ibrutinib Obinutuzumab Laboratory Biom...	18 Years -	Thomas Jefferson University
Ibrutinib in Combination With Rituximab and Lenalidomide in Treating Patients With Previously Untreated, Stage II-IV Follicular Lymphoma or Marginal Zone Lymphoma	NCT02532257	Ann Arbor Stage... Ann Arbor Stage... Ann Arbor Stage... Ann Arbor Stage... Ann Arbor Stage... Ann Arbor Stage... CD20 Positive Grade 1 Follicu... Grade 2 Follicu... Grade 3a Follic...	Ibrutinib Laboratory Biom... Lenalidomide Rituximab	18 Years -	M.D. Anderson Cancer Center

Spots Global Cancer Trial Database for ann arbor stage iv follicular lymphoma