Neoplasms

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Lymphoma

Lymphoma, Mantle-Cell

Neoplasms by Histologic Type

Lymphoproliferative Disorders

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Lymphoma, Non-Hodgkin

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Mantle Cell Lymphoma

All Drugs and Chemicals

Anti-Inflammatory Agents

Antineoplastic Agents

Antiemetics

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Antirheumatic Agents

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Anti-Infective Agents

Amino Acids

Antibodies

Antibodies, Monoclonal

Dexamethasone

Rituximab

Lenalidomide

Dexamethasone acetate

BB 1101

Immunoglobulins

Ibrutinib

Ichthammol

Antineoplastic Agents, Immunological

Immunoglobulins, Intravenous

Immunologic Factors

Glucocorticoids

Hormones

Hormone Antagonists

Antineoplastic Agents, Hormonal

Angiogenesis Inhibitors

Growth Inhibitors

HIV Protease Inhibitors

Protease Inhibitors

Enzyme Inhibitors

Tyrosine Kinase Inhibitors

Protein Kinase Inhibitors

Tyrosine

Participants receive ibrutinib PO on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Participants also receive rituximab IV on days 1, 8, 15 and 22 in course 1 and 2, on day 1 of course 3-8, and then on day 1 of every other 28-day course, lenalidomide PO on days 1-21, and dexamethasone PO weekly. Treatment with rituximab repeats every 28 days for 2 years, with lenalidomide for 1 year, and with dexamethasone for up to 2 courses in the absence of disease progression or unacceptable toxicity.

Luhua (Michael) Wang

This phase II trial studies how well ibrutinib plus rituximab and lenalidomide work in treating elderly participants with newly diagnosed mantle cell lymphoma. Ibrutinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Immunotherapy with monoclonal antibodies, such as rituximab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Drugs used in chemotherapy, such as lenalidomide, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving ibrutinib plus rituximab and lenalidomide may work better in treating elderly participants with newly diagnosed mantle cell lymphoma.

PRIMARY OBJECTIVES:

I. To evaluate the overall response rate (ORR) at 4 months of ibrutinib plus rituximab and lenalidomide in elderly patients with newly-diagnosed, untreated mantle cell lymphoma (MCL).

SECONDARY OBJECTIVES:

I. To evaluate the toxicity profile of the combination of ibrutinib plus rituximab and lenalidomide in newly diagnosed, untreated MCL.

II. To estimate the overall response rate (ORR); (partial response \[PR\] or better), the response duration (DOR), progression-free survival (PFS), time to progression (TTP) and overall survival (OS). Clinical benefit response \[(CBR) = marginal response (MR) + ORR\] will also be evaluated.

EXPLORATORY OBJECTIVES:

I. Correlative studies will be aimed at confirming the mechanism of action of the combination and to identify predictors of response or resistance to therapy.

OUTLINE:

Participants receive ibrutinib orally (PO) on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Participants also receive rituximab intravenously (IV) on days 1, 8, 15 and 22 in course 1 and 2, on day 1 of course 3-8, and then on day 1 of every other 28-day course, lenalidomide PO on days 1-21, and dexamethasone PO weekly. Treatment with rituximab repeats every 28 days for 2 years, with lenalidomide for 1 year, and with dexamethasone for up to 2 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, participants are followed up at 30 days, every 3 months for 1 year, and every 6 months thereafter.

Ibrutinib Plus Rituximab and Lenalidomide in Treating Elderly Participants With Newly Diagnosed Mantle Cell Lymphoma

A Phase II Study of Ibrutinib Plus Rituximab and Lenalidomide in Elderly Patients With Newly Diagnosed MCL

The overall response (complete response + partial response) at four months and toxicity at one month (during course 1) will be monitored simultaneously using the Bayesian approach of Thall, Simon, Estey as extended by Thall and Sung. Independence was assumed between or and toxicity, where toxicity is defined as dose-limiting toxicity (DLT) within cycle 1.

Toxicity data by type and severity will be summarized by frequency tables. For the efficacy endpoints, intend-to-treat analysis will be performed. For the toxicity endpoint, per-treated analysis will be performed to include any patient who received the treatment regardless of the eligibility nor the duration or dose of the treatment received.

Summary statistics will be provided for continuous variables. Frequency tables will be used to summarize categorical variables. The distribution of time-to-event endpoints including overall survival and progression free survival will be estimated using the method of Kaplan and Meier. Comparison of time-to-event endpoints by important subgroups will be made using the log-rank test. Cox proportional hazard regression will be employed for multivariate analysis on time-to-event outcomes.

National Cancer Institute (NCI)

M.D. Anderson Cancer Center

Symptoms and General Pathology

Recurrence

Patients receive ibrutinib PO daily on days 1-28 and rituximab IV over 4-8 hours on days 1, 8, 15, and 22 of course 1; on day 1 of courses 3-8; and on day 1 of every other course for all subsequent courses. Treatment with rituximab repeats every 28 days for up to 2 years in the absence of disease progression or unacceptable toxicity. Courses with ibrutinib repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Laboratory Biomarker Analysis

Preetesh Jain

This phase II trial studies how well ibrutinib and rituximab work in treating patients with mantle cell lymphoma that has come back or has not responded to treatment or older patients with newly diagnosed mantle cell 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 find cancer cells and help kill them. Giving ibrutinib and rituximab may be an effective treatment for mantle cell lymphoma.

PRIMARY OBJECTIVES:

I. To evaluate the response rate of ibrutinib plus rituximab in patients with relapsed and/or refractory mantle cell lymphoma (MCL).

II. To evaluate the safety and response rate of ibrutinib plus rituximab in elderly patients (\> 65) with newly-diagnosed, untreated MCL.

SECONDARY OBJECTIVES:

I. To further evaluate the toxicity profile of the combination of ibrutinib and rituximab in patients with relapsed and/or refractory MCL.

II. To estimate the overall response rate (ORR); (partial response \[PR\] or better), the response duration (DOR), progression-free survival (PFS), time to progression (TTP) and overall survival (OS) in patients with relapsed and/or refractory MCL; clinical benefit response (CBR) = (minimal response \[MR\] + ORR) will also be evaluated.

III. To estimate the response duration, PFS, time to progression (TTP), and OS in elderly patients (\> 65) with newly-diagnosed, untreated MCL.

EXPLORATORY OBJECTIVES:

I. To correlate detected gene mutations and changes in gene and/or protein expression with response to treatment.

OUTLINE:

Patients receive ibrutinib orally (PO) daily on days 1-28 and rituximab intravenously (IV) over 4-8 hours on days 1, 8, 15, and 22 of course 1; on day 1 of courses 3-8; and on day 1 of every other course for all subsequent courses. Treatment with rituximab repeats every 28 days for up to 2 years in the absence of disease progression or unacceptable toxicity. Courses with ibrutinib repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months for 1 year and then every 6 months thereafter.

Ibrutinib and Rituximab in Treating Patients With Relapsed or Refractory Mantle Cell Lymphoma or Older Patients With Newly Diagnosed Mantle Cell Lymphoma

A Phase II Study of Ibrutinib Plus Rituximab in Patients With Relapsed/Refractory Mantle Cell Lymphoma or Elderly Patients With Newly Diagnosed MCL

Overall response will be monitored using the Bayesian stopping boundaries calculated based on beta-binomial distribution.

Toxicity data will be summarized by frequency tables for all patients.

Will be assessed by the International Workshop Standardized Response Criteria for non-Hodgkin lymphoma.

Duration of response will be estimated using the method of Kaplan and Meier. Comparison by important subgroups will be made using the log-rank test. Cox proportional hazards will be employed for multivariate analysis.

Progression-free survival will be estimated using the method of Kaplan and Meier. Comparison of time-to-event endpoints by important subgroups will be made using the log-rank test. Cox proportional hazard regression will be employed for multivariate analysis on time-to-events outcomes.

Comparison of time-to-event endpoints by important subgroups will be made using the log-rank test. Cox proportional hazard regression will be employed for multivariate analysis on time-to-events outcomes.

Overall survival will be estimated using the method of Kaplan and Meier. Comparison by important subgroups will be made using the log-rank test. Cox proportional hazards will be employed for multivariate analysis.

Intend-to-treat analysis will be applied to the eligible patients.

Venetoclax

Obinutuzumab

Bendamustine Hydrochloride

Antineoplastic Agents, Alkylating

Alkylating Agents

Patients receive venetoclax PO on days 1-28 of course 1 and days 1-10 of subsequent courses, bendamustine IV on days 1 and 2, and obinutuzumab IV on days 1, 8, and 15 of course 1 and day 1 of subsequent courses. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unaccepted toxicity.

Bendamustine

Jonathon B. Cohen, MD, MS

This phase II trial studies how well bendamustine, obinutuzumab, and venetoclax work in treating patients with mantle cell lymphoma. Drugs used in chemotherapy, such as bendamustine and venetoclax, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Immunotherapy with monoclonal antibodies, such as obinutuzumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving bendamustine, obinutuzumab, and venetoclax may work better in treating patients with mantle cell lymphoma.

PRIMARY OBJECTIVE:

I. To evaluate the efficacy of the combination of bendamustine, obinutuzumab and venetoclax in patients with untreated mantle cell lymphoma.

SECONDARY OBJECTIVES:

I. To evaluate the safety and dose intensity of the combination of bendamustine, obinutuzumab and venetoclax in untreated mantle cell lymphoma.

II. To explore methods of determining molecular remission for patients with untreated mantle cell lymphoma (MCL).

III. To evaluate long-term outcomes including progression-free and overall survival for patients with untreated MCL who receive the combination.

OUTLINE:

Patients receive venetoclax orally (PO) on days 1-28 of course 1 and days 1-10 of subsequent courses, bendamustine intravenously (IV) on days 1 and 2, and obinutuzumab IV on days 1, 8, and 15 of course 1 and day 1 of subsequent courses. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unaccepted toxicity.

After completion of study treatment, patients are followed up at 45-60 days.

Bendamustine, Obinutuzumab, and Venetoclax in Patients With Untreated Mantle Cell Lymphoma

A Phase II Evaluation of Bendamustine, Obinutuzumab and Venetoclax in Patients With Untreated Mantle Cell Lymphoma

Response will be assessed by positron emission tomography (PET)/computerized tomography (CT) imaging according to the Lugano Classification for response assessment in lymphoma, developed at the 2014 International Conference on Malignant Lymphoma.

MRD will be assessed by peripheral blood using the ClonoSEQ assay available from Adaptive Biotechnologies.

Will be described using the Kaplan-Meier methodology. Some patients may undergo consolidative autologous stem cell transplant without evidence of disease progression. This will not be counted against PFS.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Ibrutinib Plus Rituximab and Lenalidomide in Treating Elderly Participants With Newly Diagnosed Mantle Cell Lymphoma	NCT03232307	CCND1 Positive CD20-Positive N... Mantle Cell Lym...	Dexamethasone Ibrutinib Lenalidomide Rituximab	66 Years -	M.D. Anderson Cancer Center
Ibrutinib and Rituximab in Treating Patients With Relapsed or Refractory Mantle Cell Lymphoma or Older Patients With Newly Diagnosed Mantle Cell Lymphoma	NCT01880567	CCND1 Positive CCND2 Positive CCND3 Positive CD20 Positive Mantle Cell Lym... Recurrent Mantl... Refractory Mant...	Ibrutinib Laboratory Biom... Rituximab	18 Years -	M.D. Anderson Cancer Center
Bendamustine, Obinutuzumab, and Venetoclax in Patients With Untreated Mantle Cell Lymphoma	NCT03872180	CCND1 Positive Mantle Cell Lym... t(11;14) Positi...	Bendamustine Obinutuzumab Venetoclax	18 Years -	Emory University
Bendamustine, Obinutuzumab, and Venetoclax in Patients With Untreated Mantle Cell Lymphoma	NCT03872180	CCND1 Positive Mantle Cell Lym... t(11;14) Positi...	Bendamustine Obinutuzumab Venetoclax	18 Years -	Emory University
Ibrutinib and Rituximab in Treating Patients With Relapsed or Refractory Mantle Cell Lymphoma or Older Patients With Newly Diagnosed Mantle Cell Lymphoma	NCT01880567	CCND1 Positive CCND2 Positive CCND3 Positive CD20 Positive Mantle Cell Lym... Recurrent Mantl... Refractory Mant...	Ibrutinib Laboratory Biom... Rituximab	18 Years -	M.D. Anderson Cancer Center

Spots Global Cancer Trial Database for ccnd1 positive