Neoplasms

Blood and Lymph Conditions

Immune System Diseases

All Conditions

Rare Diseases

Lymphoma

Lymphoma, Mantle-Cell

Neoplasms by Histologic Type

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Lymphoma, Non-Hodgkin

Lymphosarcoma

Mantle Cell Lymphoma

All Drugs and Chemicals

Antineoplastic Agents

Antibodies

Antibodies, Monoclonal

Venetoclax

Obinutuzumab

Lenalidomide

Immunoglobulins

Muromonab-CD3

Antineoplastic Agents, Immunological

Immunoglobulins, Intravenous

Antibodies, Bispecific

Immunologic Factors

Angiogenesis Inhibitors

Growth Inhibitors

Patients receive venetoclax PO, obinutuzumab IV, glofitamab IV, and lenalidomide IV on study. Patients undergo bone marrow biopsy, blood sample collection, and CT scan and/or PET scan throughout the study. Patients may undergo tumor biopsy throughout the study.

Biopsy

Biospecimen Collection

Bone Marrow Biopsy

Computed Tomography

Glofitamab

Positron Emission Tomography

Tycel J. Phillips

Tycel J Phillips

This phase I/II trial tests the safety and effectiveness of glofitamab (with obinutuzumab pretreatment), venetoclax, and lenalidomide in treating patients with newly diagnosed, high risk mantle cell lymphoma. Glofitamab and obinutuzumab are monoclonal antibodies that may interfere with the ability of cancer cells to grow and spread. Venetoclax is in a class of medications called B-cell lymphoma-2 (BCL-2) inhibitors. It may stop the growth of cancer cells by blocking Bcl-2, a protein needed for cancer cell survival. Lenalidomide works by helping the immune system kill cancer cells and by helping the bone marrow to produce normal blood cells. Giving venetoclax, glofitamab with obinutuzumab, and lenalidomide together may kill more cancer cells in patients with newly diagnosed, high risk mantle cell lymphoma.

PRIMARY OBJECTIVE:

I. To evaluate the efficacy of venetoclax, glofitamab and lenalidomide in newly diagnosed patients with high risk mantle cell lymphoma (MCL) as measured by progression free survival (PFS) at 24 months.

SECONDARY OBJECTIVES:

I. To evaluate the safety and tolerability of the combination of lenalidomide, venetoclax and glofitamab in patients with newly diagnosed MCL.

II. To determine overall response rate (ORR) of patients with newly diagnosed MCL who are treated with the combination of lenalidomide, venetoclax and glofitamab.

III. To determine the complete remission rate of the combination in patients with untreated MCL.

IV. To determine the PFS at 24 months of the patients with p53 mutation versus (vs.) those who lack this abnormality.

V. To determine duration of response of patients treated with the combination lenalidomide, venetoclax and glofitamab.

VI. To determine progression free survival of patients who obtain minimal residual disease (MRD) negativity.

EXPLORATORY OBJECTIVES:

I. To evaluate changes in T-cell repertoire at baseline and on treatment based on exposure to glofitamab utilizing immune-sequence (seq) assay.

II. To determine if any other baseline genetic feature impacts response and/or duration of response to the treatment regimen.

III. To evaluate outcomes of treated patients based on segregation into distinct MCL clusters using whole exome sequencing (WES).

IV. To determine if rates of cytokine release syndrome (CRS)/immune effector cell-associated neurotoxicity syndrome (ICANS) are impacted by co-administration of lenalidomide/venetoclax in conjunction with glofitamab.

V. To determine if utilization and efficacy of tocilizumab for CRS is impacted by co-administration of lenalidomide/venetoclax in conjunction with glofitamab.

OUTLINE:

Patients receive venetoclax orally (PO), obinutuzumab intravenously (IV), glofitamab IV, and lenalidomide IV on study. Patients undergo bone marrow biopsy, blood sample collection, and computed tomography (CT) scan and/or positron emission tomography (PET) scan throughout the study. Patients may undergo tumor biopsy throughout the study.

Patients are followed-up every 3 months for the first two years, and then every 6 months starting in the third year until disease recurrence.

Glofitamab With Obinutuzumab, Venetoclax, and Lenalidomide for the Treatment of Patients With Newly Diagnosed High Risk Mantle Cell Lymphoma

Phase 1/2 Study of the Combination of Glofitamab, Venetoclax and Lenalidomide in Patients With Newly Diagnosed High Risk Mantle Cell Lymphoma

Adverse events will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0.

Adverse events of special interest including neurotoxicity, cytopenias, and infections are graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 5. Cytokine release syndrome is graded according to American Society for Transplantation and Cellular Therapy criteria.

Determined by revised Lugano 2016 criteria. Includes complete response and partial response.

National Cancer Institute (NCI)

City of Hope Medical Center

Symptoms and General Pathology

Recurrence

Amino Acids

Acalabrutinib

Tyrosine Kinase Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Tyrosine

Patients receive acalabrutinib PO BID on days 1-28. Starting cycle 2 day 1, patients also receive venetoclax PO daily. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Luhua (Michael) Wang

This phase II trial studies how well venetoclax and acalabrutinib work in treating patients with mantle cell lymphoma that did not respond to previous treatment or has come back. Venetoclax may cause cancer cell death by blocking the mechanism that cancer cells use to stay alive. Acalabrutinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving venetoclax and acalabrutinib together may kill more cancer cells in patients with mantle cell lymphoma.

PRIMARY OBJECTIVES:

I. To evaluate the efficacy of a combination of venetoclax and acalabrutinib, in patients with previously treated relapsed/refractory mantle cell lymphoma (MCL).

SECONDARY OBJECTIVES:

I. To evaluate the efficacy of this combination regimen in previously treated subjects with relapsed/refractory MCL with overall response rate (ORR), duration of response (DOR), event free survival (EFS), progression free survival (PFS), and overall survival (OS).

II. To evaluate the safety and tolerability of venetoclax and acalabrutinib in previously treated subjects with relapsed/refractory MCL.

CORRELATIVE/TRANSLATIONAL COMPONENT OBJECTIVES:

I. Sequential peripheral blood (PB)/plasma/tissue fine needle aspirate will be stored.

II. Clonal evolution with targeted sequencing (seq) and/or whole exome sequencing (WES) in sequential samples.

III. Pattern of mutation changes with Bruton tyrosine kinase inhibitor (BTKi) or with venetoclax resistance.

IV. Response predictors - mutations, cytokine-chemokines, clonal evolution (CE).

V. Minimal residual disease (MRD) assay using circulating tumor deoxyribonucleic acid (ctDNA) analysis, flow cytometry at various time points from peripheral blood (PB)/ bone marrow (BM).

VI. Sequential immunologic studies with cytokines/chemokines, T cell numbers, and immunoglobulins (Ig).

VII. Tissue microenvironmental studies with simultaneous assessment of PB, BM and lymph nodes for gene expression profiling (GEP), single cell seq, ribonucleic acid (RNA) seq and clonal heterogeneity and the impact of acalabrutinib - venetoclax (A-V) treatment.

OUTLINE: This is a dose escalation study of venetoclax.

Patients receive acalabrutinib orally (PO) twice daily (BID) on days 1-28. Starting cycle 2 day 1, patients also receive venetoclax PO daily. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up within 30 days, then every 4 months for 2 years, then every 6 months for the next 2 years, and then annually thereafter.

Venetoclax and Acalabrutinib in Treating Patients With Relapsed or Refractory Mantle Cell Lymphoma

An Open Label, Phase II Investigator Initiated Study of Venetoclax and Acalabrutinib in Previously Treated Relapsed/Refractory Patients With Mantle Cell Lymphoma (MCL)

Assessed by Lugano criteria - positron emission tomography (PET)-computed tomography, and in a subset of patients by bone marrow flow cytometry, circulating tumor deoxyribonucleic acid and endoscopy if at baseline there is gut involvement. Response will be calculated separately with and without knowledge of the PET result by International Working Group criteria, in order to provide context in relation to historical control data. Will estimate the CR along with the 95% credible interval.

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.

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

M.D. Anderson Cancer Center

Anti-Infective Agents

Antirheumatic Agents

Anti-Inflammatory Agents

Antiemetics

Gastrointestinal Agents

Dermatologic Agents

Reproductive Control Agents

Micronutrients

Hematinics

Vitamins

Cytarabine

Cyclophosphamide

Doxorubicin

Liposomal doxorubicin

Dexamethasone

Methotrexate

Rituximab

Vincristine

Daunorubicin

Dexamethasone acetate

BB 1101

Ibrutinib

Ichthammol

Immunosuppressive Agents

Antineoplastic Agents, Alkylating

Alkylating Agents

Glucocorticoids

Hormones

Hormone Antagonists

Antineoplastic Agents, Hormonal

HIV Protease Inhibitors

Protease Inhibitors

Anti-Bacterial Agents

Antibiotics, Antitubercular

Antimetabolites

Folic Acid

Vitamin B Complex

Folic Acid Antagonists

Antiviral Agents

Tubulin Modulators

Antimitotic Agents

Folinic Acid

Folate

Vitamin B9

PART I (IBRUTINIB PLUS RITUXIMAB): Patients receive ibrutinib PO QD on days 1-28 and rituximab IV over 6-8 hours on days 1, 8, 15, and 22 of cycle 1 and then over 4 hours on day 1 of cycles 3-12. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity or until patients achieve complete response.

PART II (CONSOLIDATION THERAPY): Patients receive rituximab IV over 6 hours on day 1; dexamethasone PO or IV on days 1-4; cyclophosphamide IV over 3 hours BID on days 2-4; doxorubicin hydrochloride IV over 15-30 minutes on day 5; and vincristine sulfate IV over 15-30 minutes on day 5 of cycles 1, 3, 5, and 7. Patients also receive rituximab IV over 6 hours on day 1; methotrexate IV over 24 hours on day 2; and cytarabine IV over 2 hours BID on days 3 and 4 of cycles 2, 4, 6, and 8. Treatment repeats every 28 days for up to 8 cycles in the absence of disease progression or unacceptable toxicity.

Doxorubicin Hydrochloride

Laboratory Biomarker Analysis

Vincristine Sulfate

This phase II trial studies how well ibrutinib, rituximab, and consolidation chemotherapy consisting of cyclophosphamide, vincristine sulfate, doxorubicin hydrochloride, dexamethasone, methotrexate, and cytarabine work in treating young 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. 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 cyclophosphamide, vincristine sulfate, doxorubicin hydrochloride, dexamethasone, methotrexate, and cytarabine, 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 more than one drug (combination chemotherapy) may kill more cancer cells. Giving ibrutinib together with rituximab and consolidation chemotherapy may be a better treatment for mantle cell lymphoma.

PRIMARY OBJECTIVES:

I. To evaluate the response rate of ibrutinib plus rituximab in young newly diagnosed mantle cell lymphoma (MCL) including young high-risk patients.

SECONDARY OBJECTIVES:

I. To evaluate the progression free survival of ibrutinib plus rituximab with rituximab - cyclophosphamide, vincristine (vincristine sulfate), doxorubicin (doxorubicin hydrochloride), and dexamethasone (hyper-CVAD) consolidation in newly diagnosed MCL patients and in high-risk patients.

II. To further evaluate the toxicity profile of the ibrutinib/rituximab combination and consolidation therapy.

III. To estimate the rate of complete response (CR) prior to and following consolidation therapy.

IV. To estimate the response duration and overall survival. V. To analyze progression free survival in a subgroup of patients presenting with high risk features after receiving an additional 2 years of maintenance therapy with rituximab and ibrutinib at doses used in part 1 of the study, starting after part 2 of the study ends.

OUTLINE:

PART I (IBRUTINIB PLUS RITUXIMAB): Patients receive ibrutinib orally (PO) once daily (QD) on days 1-28 and rituximab intravenously (IV) over 6-8 hours on days 1, 8, 15, and 22 of cycle 1 and then over 4 hours on day 1 of cycles 3-12. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity or until patients achieve complete response.

PART II (CONSOLIDATION THERAPY): Patients receive rituximab IV over 6 hours on day 1; dexamethasone PO or IV on days 1-4; cyclophosphamide IV over 3 hours twice daily (BID) on days 2-4; doxorubicin hydrochloride IV over 15-30 minutes on day 5; and vincristine sulfate IV over 15-30 minutes on day 5 of cycles 1, 3, 5, and 7. Patients also receive rituximab IV over 6 hours on day 1; methotrexate IV over 24 hours on day 2; and cytarabine IV over 2 hours BID on days 3 and 4 of cycles 2, 4, 6, and 8. Treatment repeats every 28 days for up to 8 cycles in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 4 months for 2 years, every 6 months for 2 years, and then annually thereafter.

Ibrutinib, Rituximab, and Consolidation Chemotherapy in Treating Young Patients With Newly Diagnosed Mantle Cell Lymphoma

A Phase II Study of Ibrutinib Plus Rituximab With Hyper-CVAD Consolidation in Newly Diagnosed Young Patients With Mantle Cell Lymphoma: A Window Period for Bioimmunotherapy Before Chemotherapy

Will be monitored using the Bayesian stopping boundaries calculated based on beta-binomial distribution. Logistic regression will be utilized to assess the effect of patient prognostic factors on the response rate.

Will be monitored using the Bayesian stopping boundaries calculated based on beta-binomial distribution. Logistic regression will be utilized to assess the effect of patient prognostic factors on the toxicity rate. Toxicity data by type and severity will be summarized by frequency tables.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Glofitamab With Obinutuzumab, Venetoclax, and Lenalidomide for the Treatment of Patients With Newly Diagnosed High Risk Mantle Cell Lymphoma	NCT05861050	Blastoid Varian... Mantle Cell Lym... Pleomorphic Var...	Biopsy Biospecimen Col... Bone Marrow Bio... Computed Tomogr... Glofitamab Lenalidomide Obinutuzumab Positron Emissi... Venetoclax	18 Years - 80 Years	City of Hope Medical Center
Venetoclax and Acalabrutinib in Treating Patients With Relapsed or Refractory Mantle Cell Lymphoma	NCT03946878	Blastoid Varian... CCND1 Protein O... CD20 Positive CD5 Positive FCER2 Negative Pleomorphic Var... Recurrent Mantl... Refractory Mant... t(11;14)(q13;q3...	Acalabrutinib Venetoclax	18 Years -	M.D. Anderson Cancer Center
Ibrutinib, Rituximab, and Consolidation Chemotherapy in Treating Young Patients With Newly Diagnosed Mantle Cell Lymphoma	NCT02427620	Blastoid Varian... Mantle Cell Lym... Pleomorphic Var...	Cyclophosphamid... Cytarabine Dexamethasone Doxorubicin Doxorubicin Hyd... Ibrutinib Laboratory Biom... Methotrexate Rituximab Vincristine Vincristine Sul...	18 Years - 65 Years	M.D. Anderson Cancer Center
Glofitamab With Obinutuzumab, Venetoclax, and Lenalidomide for the Treatment of Patients With Newly Diagnosed High Risk Mantle Cell Lymphoma	NCT05861050	Blastoid Varian... Mantle Cell Lym... Pleomorphic Var...	Biopsy Biospecimen Col... Bone Marrow Bio... Computed Tomogr... Glofitamab Lenalidomide Obinutuzumab Positron Emissi... Venetoclax	18 Years - 80 Years	City of Hope Medical Center
Glofitamab With Obinutuzumab, Venetoclax, and Lenalidomide for the Treatment of Patients With Newly Diagnosed High Risk Mantle Cell Lymphoma	NCT05861050	Blastoid Varian... Mantle Cell Lym... Pleomorphic Var...	Biopsy Biospecimen Col... Bone Marrow Bio... Computed Tomogr... Glofitamab Lenalidomide Obinutuzumab Positron Emissi... Venetoclax	18 Years - 80 Years	City of Hope Medical Center

Spots Global Cancer Trial Database for pleomorphic variant mantle cell lymphoma