NCT02073097

Carfilzomib, Rituximab, and Combination Chemotherapy in Treating Patients With Diffuse Large B-Cell Lymphoma

A Phase I/II Study of Carfilzomib in Combination With R-CHOP (CR-CHOP) for Patients With Diffuse Large B-cell Lymphoma

• Status: Completed
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 48 (actual)
• Sponsor: Case Comprehensive Cancer Center · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This phase I/II trial studies the side effects and best dose of carfilzomib when given together with rituximab and combination chemotherapy and to see how well they work in treating patients with diffuse large B-cell lymphoma. Carfilzomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies, such as rituximab, can block cancer growth by finding cancer cells and helping kill them. Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. It is not known if carfilzomib in combination with R-CHOP is better or worse than R-CHOP alone in treating patients with diffuse large b-cell lymphoma.

Detailed description

PRIMARY OBJECTIVES: I. To determine the safety of carfilzomib in combination with rituximab-cyclophosphamide, doxorubicin hydrochloride, vincristine, and prednisone (R-CHOP) (CR-CHOP) in patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL) and identify a recommended phase II dose (RP2D). (Phase I) SECONDARY OBJECTIVES: I. To determine if CR-CHOP improves the rates of 1-year progression free survival (PFS) and overall survival (OS) in non-germinal center (non-GC) DLBCL patients relative to historical controls treated with R-CHOP(Phase II) II. To determine response rates (complete and partial remission) in non-GC DLBCL patients treated with CR-CHOP and compare to historical controls treated with R-CHOP. III. Because a proportion (\~10%) of patients classified as non-GC by immunohistochemical (IHC) algorithms may not have the activated B-cells (ABC) subtyped of DLBCL, an exploratory secondary objective will compare the PFS, OS and response rates of the ABC subgroup of patients with DLBCL as determined by the Gene Expression Profiling with those of the overall group of non-GC DLBCL. OUTLINE: This is a phase I, dose-escalation study of carfilzomib followed by a phase II study. Patients receive rituximab intravenously (IV) over at least 90 minutes, cyclophosphamide IV over 30-60 minutes, doxorubicin hydrochloride IV over 3-5 minutes, vincristine sulfate IV over 1 minute on day 1, and prednisone orally (PO) on days 1-5. Patients also receive carfilzomib IV over 30 minutes on days 1, 2, 8 and 9. Courses repeat every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up at 30 days and at 6, 12, and 24 months.

Conditions

• Contiguous Stage II Adult Diffuse Large Cell Lymphoma
• Noncontiguous Stage II Adult Diffuse Large Cell Lymphoma
• Stage I Adult Diffuse Large Cell Lymphoma
• Stage III Adult Diffuse Large Cell Lymphoma
• Stage IV Adult Diffuse Large Cell Lymphoma

Interventions

Type	Name	Description
DRUG	Carfilzomib	Given IV, according to dose level. Cohorts begin with dose level (DL)1, escalated in standard 3+3 design to identify a recommended phase 2 dose DL (-2) 11 mg/m2 on day 1 and 2 every 21 days, cycles 1-6 DL (-1) 15 mg/m2 on days 1 and 2 every 21 days, cycles 1-6 DL (1) 20 mg/m2 days 1,2 every 21 days, cycles 1-6 DL (2) 20 mg/m2 days 1,2 of cycle 1 followed by 27 mg/m2 days 1,2 every 21 days for cycles 2-6. DL (3) 20 mg/m2 days 1,2 of cycle 1 followed by 36 mg/m2 days 1,2 every 21 days for cycles 2-6. DL(4) 20 mg/m2 days 1,2 of cycle 1 followed by 45 mg/m2 days 1,2 every 21 days for cycles 2-6 DL (5) 20 mg/m2 days 1,2 of cycle 1 followed by 56 mg/m2 days 1,2 every 21 days for cycles 2-6
BIOLOGICAL	Rituximab	Given IV (375mg/m\^2)
DRUG	Cyclophosphamide	Given IV (750mg/m\^2)
DRUG	Doxorubicin hydrochloride	Given IV (50mg/m\^2)
DRUG	Vincristine sulfate	Given IV (1.4mg/m\^2)
DRUG	Prednisone	Given PO (100mg)
DRUG	Pegfilgrastim	6 mg SC day 4 (every 21 days). Filgrastim 300 or 480 mcg IV/SC daily days 1-10 may be substituted if pegfilgrastim is not available. ONPROTM is also an acceptable method of administration.
DRUG	Acyclovir	PO (400mg)

Timeline

• Start date: 2015-01-28
• Primary completion: 2021-07-20
• Completion: 2023-06-29
• First posted: 2014-02-27
• Last updated: 2024-05-29
• Results posted: 2024-05-29

Locations

3 sites across 1 country: United States

Regulatory

• FDA-regulated drug study