NCT03701321

Daratumumab, Bortezomib, and Dexamethasone With or Without Venetoclax in Treating Patients With Relapsed or Refractory Multiple Myeloma

Phase 1/2 Study of Daratumumab, Bortezomib, Dexamethasone With or Without Venetoclax in Relapsed/Refractory Multiple Myeloma With Assessment for t(11;14) Status

• Status: Withdrawn
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 0 (actual)
• Sponsor: National Cancer Institute (NCI) · NIH
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This phase I/II trial studies the side effects and best dose of venetoclax when given together with daratumumab, bortezomib, and dexamethasone, and how well they work in treating patients with multiple myeloma that has come back (relapsed) or does not respond to treatment (refractory). Drugs used in chemotherapy, such as venetoclax and dexamethasone, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Immunotherapy with monoclonal antibodies, such as daratumumab, may help the body's immune system attack the tumor, and may interfere with the ability of tumor cells to grow and spread. Bortezomib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving venetoclax with daratumumab, bortezomib, and dexamethasone may work better in treating patients with relapsed or refractory multiple myeloma compared to standard of care treatment, including chemotherapy.

Detailed description

PRIMARY OBJECTIVES: I. To determine the dose limiting toxicities and the recommended phase II dose of venetoclax in combination with daratumumab, bortezomib, and dexamethasone for patients with relapsed/refractory multiple myeloma. (Phase I) II. To evaluate the safety of venetoclax (VEN) in combination with bortezomib and dexamethasone (DVd). (Phase I) III. To compare efficacy of DVd-VEN versus DVd as measured by minimal residual disease negative rate after 8 cycles of therapy. (Phase II) IV. To inform the role of t(11;14) as a biomarker in a subsequent evaluation of the regimen. (Phase II) SECONDARY OBJECTIVES: I. To compare rates of very good partial response between arms. II. To assess improvement in progression-free and overall survival with the addition of VEN. III. To evaluate the safety of VEN in combination with DVd and compare overall toxicity rates between arms. IV. To assess association of cycle 8 minimal residual disease (MRD) status with overall and progression-free survival. V. To estimate the impact of t(11;14) status on very good partial response, overall and progression-free survival. EXPLORATORY OBJECTIVES: I. To measure treatment exposure and adherence. II. To estimate time to progression with the addition of VEN. III. To measure MRD levels longitudinally and assess the kinetics of relapse. IV. To assess association of MRD status after 8 cycles with survival outcomes. V. To evaluate agreement and discordance between methods determining disease-free status. OUTLINE: This is a phase I, dose-escalation study of venetoclax followed by a phase II study. PHASE I: Patients receive daratumumab intravenously (IV) on days 1, 8, and 15 of cycles 1-3 and on day 1 of subsequent cycles, bortezomib subcutaneously (SC) on days 1, 8, and 15 of cycles 1-8, dexamethasone orally (PO) on days 1, 8, and 15 of cycles 1-8, and venetoclax PO once daily (QD) on days 1-21. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. PHASE II: Patients are randomized to 1 of 2 arms. ARM D: Patients receive venetoclax PO QD on days 1-21, daratumumab IV on days 1, 8, and 15 of cycles 1-3 and on day 1 of subsequent cycles, bortezomib SC on days 1, 8, and 15 of cycles 1-8, and dexamethasone PO on days 1, 8, and 15 of cycles 1-8. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. ARM E: Patients receive daratumumab IV on days 1, 8, and 15 of cycles 1-3 and on day 1 of subsequent cycles, bortezomib SC on days 1, 8, and 15 of cycles 1-8, and dexamethasone PO on days 1, 8, and 15 of cycles 1-8. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up periodically for 10 years.

Conditions

• Recurrent Plasma Cell Myeloma
• Refractory Plasma Cell Myeloma

Interventions

Type	Name	Description
DRUG	Bortezomib	Given SC
BIOLOGICAL	Daratumumab	Given IV
DRUG	Dexamethasone	Given PO
DRUG	Venetoclax	Given PO

Timeline

• Start date: 2019-01-25
• Primary completion: 2020-05-28
• Completion: 2020-05-28
• First posted: 2018-10-10
• Last updated: 2023-09-26

Locations

3 sites across 1 country: United States

Regulatory

• FDA-regulated drug study