Belantamab Mafodotin, Lenalidomide, and Daratumumab for the Treatment of Relapsed, Refractory, or Previously Untreated Multiple Myeloma

Plasma Cell Myeloma Clinical Trial

Official title: Randomized Phase 1 / 2 Trial of Belantamab Mafodotin, Lenalidomide, and Daratumumab in Relapsed or Newly Diagnosed Multiple Myeloma Patients

Status Completed

Clinical Trial Summary

This phase I/II trial studies the best dose and effect of belantamab mafodotin given together with lenalidomide and daratumumab in treating patients with multiple myeloma that has come back (relapsed), does not respond to treatment (refractory) or for which the patient has not received treatment in the past (previously untreated). Belantamab mafodotin is a monoclonal antibody, called belantamab, linked to a chemotherapy drug, called mafodotin. Belantamab is a form of targeted therapy because it attaches to specific molecules (receptors) on the surface of cancer cells, known as BCMA receptors, and delivers mafodotin to kill them. Lenalidomide is an immunomodulatory drug (altering the immune effects on the tumor cell). Daratumumab is a drug that is a monoclonal antibody that is directed towards a protein on the myeloma cell. Giving belantamab mafodotin together with lenalidomide and daratumumab may kill more cancer cells.

Clinical Trial Description

PRIMARY OBJECTIVES:

I. To determine the maximum tolerated dose (MTD) of belantamab mafodotin (belantamab) in combination with daratumumab and lenalidomide in patients with relapsed or refractory multiple myeloma. (Phase I) II. To assess the confirmed complete response rate following induction therapy with belantamab, daratumumab, and lenalidomide (bortezomib-dexamethasone-rituximab [BDR]), OR alternating cycles of daratumumab, lenalidomide, dexamethasone and belantamab, lenalidomide and dexamethasone, when used as initial therapy in patients with previously untreated symptomatic multiple myeloma patients. (Phase II)

SECONDARY OBJECTIVES:

I. To describe the toxicities associated with the combination of belantamab, daratumumab, and lenalidomide when used as initial therapy in patients with relapsed multiple myeloma. (Phase I) II. To assess the overall response rate (ORR) and >= very good partial response (VGPR) rate of belantamab, daratumumab, and lenalidomide (BDR) (Phase II), OR alternating cycles of daratumumab, lenalidomide, dexamethasone and belantamab, lenalidomide and dexamethasone. (Phase II) III. To assess the progression free survival and overall survival among patients with previously untreated symptomatic multiple myeloma following treatment with belantamab, daratumumab, and lenalidomide (BDR) (Phase II), OR alternating cycles of daratumumab, lenalidomide, dexamethasone and belantamab, lenalidomide and dexamethasone. (Phase II) IV. To assess the time to response (defined as the time between the date of first dose and the first documented evidence of a partial response or better) following treatment with belantamab, daratumumab, and lenalidomide (BDR) (Phase II), OR alternating cycles of daratumumab, lenalidomide, dexamethasone and belantamab, lenalidomide and dexamethasone. (Phase II) V. To describe the toxicities associated with belantamab, daratumumab, and lenalidomide (BDR) (Phase II), OR alternating cycles of daratumumab, lenalidomide, dexamethasone and belantamab, lenalidomide and dexamethasone. (Phase II)

CORRELATIVE RESEARCH OBJECTIVE:

I. Examine the rate of minimal residual disease (MRD) negativity following induction therapy with the combination of belantamab, daratumumab, and lenalidomide (BDR) (Phase II), OR alternating cycles of daratumumab, lenalidomide, dexamethasone and belantamab, lenalidomide and dexamethasone. (Phase II)

OUTLINE: This is a phase I dose-escalation study of belantamab mafodotin, followed by a phase II study.

PHASE I:

INDUCTION: Patients receive belantamab mafodotin intravenously (IV) over 30 minutes on day 1, lenalidomide orally (PO) once daily (QD) on days 1-21, and daratumumab IV over 90 minutes on days 1, 8, 15, and 22 of cycles 1 and 2, days 1 and 15 of cycles 3-6, and day 1 of subsequent cycles. Treatment with belantamab mafodotin repeats every 56 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. Treatment with lenalidomide and daratumumab repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity.

MAINTENANCE: Beginning cycle 13, patients receive belantamab mafodotin IV over 30 minutes on day 1 of odd number cycles, lenalidomide PO QD on days 1-21, and daratumumab IV over 90 minutes on day 1. Treatment with belantamab mafodotin repeats every 56 days, and every 28 days for lenalidomide and daratumumab in the absence of disease progression or unacceptable toxicity. Treatment with belantamab mafodotin repeats every 56 days (every other cycle) for up to 24 cycles in the absence of disease progression or unacceptable toxicity. Treatment with lenalidomide and daratumumab repeats every 28 days for up to 24 cycles in the absence of disease progression or unacceptable toxicity.

PHASE II: Patients are randomized to 1 of 2 arms.

ARM A:

INDUCTION: Patients receive belantamab mafodotin IV over 30 minutes on day 1 of odd number cycles, lenalidomide PO QD on days 1-21, and daratumumab IV over 90 minutes on days 1, 8, 15, and 22 of cycles 1 and 2, days 1 and 15 of cycles 3-6, and day 1 of subsequent cycles. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity.

MAINTENANCE: Beginning cycle 13, patients receive belantamab mafodotin IV over 30 minutes on day 1 of odd number cycles (starting cycle 13), lenalidomide PO QD on days 1-21, and daratumumab IV over 90 minutes on day 1. Treatment repeats every 28 days for up to 24 cycles in the absence of disease progression or unacceptable toxicity.

ARM B:

INDUCTION: Patients receive belantamab mafodotin IV over 30 minutes on day 1 of cycles 2, 4, 6, 8, 10, and 12, lenalidomide PO QD on days 1-21, daratumumab IV over 90 minutes on days 1, 8, 15, and 22 of cycles 1 and 3, and days 1 and 15 on cycles 5, 7, 9, and 11. Patients also receive dexamethasone PO on days 1, 8, 15 and 22. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity.

MAINTENANCE: Beginning cycle 13, patients receive belantamab mafodotin IV over 30 minutes on day 1 of even numbered cycles, lenalidomide PO QD on days 1-21, and daratumumab IV over 90 minutes on day 1 of odd numbered cycles. Treatment repeats every 28 days for up to 24 cycles in the absence of disease progression or unacceptable toxicity.

Additionally, all patients undergo blood sample collection, X-ray skeletal survey or whole body low dose computed tomography (CT), bone marrow aspiration and biopsy throughout study.

After completion of study treatment, patients are followed up at 30 days. ;

Related Conditions & MeSH terms

• Multiple Myeloma
• Neoplasms, Plasma Cell
• Plasma Cell Myeloma
• Recurrent Plasma Cell Myeloma
• Refractory Plasma Cell Myeloma

• NCT number: NCT04892264
• Study type: Interventional
• Source: Mayo Clinic
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: June 3, 2021
• Completion date: March 18, 2024