NCT02427620

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

• Status: Active Not Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 131 (estimated)
• Sponsor: M.D. Anderson Cancer Center · Academic / Other
• Sex: All
• Age: 18 Years – 65 Years
• Healthy volunteers: Not accepted

Summary

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.

Detailed description

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.

Conditions

• Blastoid Variant Mantle Cell Lymphoma
• Mantle Cell Lymphoma
• Pleomorphic Variant Mantle Cell Lymphoma

Interventions

Type	Name	Description
DRUG	Cyclophosphamide	Given IV
DRUG	Cytarabine	Given IV
DRUG	Dexamethasone	Given PO or IV
DRUG	Doxorubicin	Given IV
DRUG	Doxorubicin Hydrochloride	Given IV
DRUG	Ibrutinib	Given PO
OTHER	Laboratory Biomarker Analysis	Correlative studies
DRUG	Methotrexate	Given IV
BIOLOGICAL	Rituximab	Given IV
DRUG	Vincristine	Given IV
DRUG	Vincristine Sulfate	Given IV

Timeline

• Start date: 2015-06-03
• Primary completion: 2027-06-30
• Completion: 2027-06-30
• First posted: 2015-04-28
• Last updated: 2025-11-21

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study