NCT06948084

Testing the Investigational Medication Combination of Daratumumab and Teclistamab Compared to the Usual Treatment (Daratumumab, Pomalidomide, Dexamethasone or Daratumumab, Carfilzomib, Dexamethasone) for Patients With High-risk Multiple Myeloma Refractory or in First Relapse

A Randomized Phase II Trial for High-Risk Multiple Myeloma That is Refractory or in First Relapse With Daratumumab, Teclistamab (DT) Versus Daratumumab, Pomalidomide, Dexamethasone (DPd) or Daratumumab, Carfilzomib, Dexamethasone (DKd)

• Status: Not Yet Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 80 (estimated)
• Sponsor: National Cancer Institute (NCI) · NIH
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This phase II trial compares the effect of the combination of daratumumab-hyaluronidase (daratumumab) and teclistamab to the usual treatment of daratumumab, pomalidomide, dexamethasone or daratumumab, carfilzomib and dexamethasone in treating patients with multiple myeloma that has not responded to previous treatment (refractory) or that has come back after a period of improvement (relapsed). Daratumumab is in a class of medications called monoclonal antibodies. It binds to a protein called CD38, which is found on some types of immune cells and cancer cells, including myeloma cells. Daratumumab may block CD38 and help the immune system kill cancer cells. Teclistamab is a bispecific antibody that can bind to two different antigens at the same time. Teclistamab binds to B-cell maturation antigen, a protein found on some B-cells and myeloma cells, and CD3 on T-cells (a type of white blood cell) and may interfere with the ability of cancer cells to grow and spread. Pomalidomide is in a class of medications called immunomodulatory agents. It works by helping the immune system kill cancer cells and by helping the bone marrow to produce normal blood cells. Dexamethasone is in a class of medications called corticosteroids. It is used to reduce inflammation and lower the body's immune response to help lessen the side effects of chemotherapy drugs. Carfilzomib, a type of proteasome inhibitor, blocks the action of enzymes called proteasomes, which may help keep cancer cells from growing and may kill them. Giving daratumumab and teclistamab may be more effective than the usual treatment of daratumumab, pomalidomide, dexamethasone or daratumumab, carfilzomib and dexamethasone in reducing myeloma cells to undetectable levels in patients with relapsed or refractory multiple myeloma.

Detailed description

PRIMARY OBJECTIVE: I. To determine whether patients with high-risk multiple myeloma (MM) that is refractory or in first relapse randomized to daratumumab and recombinant human hyaluronidase (daratumumab-hyaluronidase) in combination with teclistamab (DT) have superior efficacy measured by minimal residual disease (MRD)-negative status after 6 cycles of therapy compared to investigator's choice of daratumumab-hyaluronidase, pomalidomide and dexamethasone (DPd) or daratumumab-hyaluronidase, carfilzomib and dexamethasone (DKd). SECONDARY CLINICAL OBJECTIVES: I. To compare toxicity rates up to 6 cycles and overall on treatment between arms. II. To compare progression-free and overall survival between arms. III. To evaluate best response per International Myeloma Working Group (IMWG) criteria after 6 cycles and overall on treatment. IV. To evaluate safety and tolerability. EXPLORATORY CLINICAL OBJECTIVES: I. To evaluate treatment exposure and adherence. II. To evaluate time to progression and event free survival. III. To evaluate association of MRD-negative status after 6 cycles with best response per IMWG criteria and time to event outcomes. EXPLORATORY THROMBOEMBOLISM RISK OBJECTIVES: I. To estimate cumulative incidence of venous and arterial thromboembolic events. II. To calculate IMPEDE and SAVED risk scores at baseline and at time of venous thromboembolic event. III. To validate IMPEDE and SAVED risk stratification models. IV. To describe thromboprophylaxis strategies on treatment and assess the association with venous and arterial thromboembolic events. V. To estimate incidence of clinically significant (major) bleeding events and assess association with thromboprophylaxis strategy. VI. To assess the association of venous and arterial thromboembolic events and overall survival. OUTLINE: Patients are randomized to 1 of 2 arms. ARM A: Patients are assigned to 1 of 2 treatments per investigator's choice. Treatment I (DPD): Patients receive daratumumab-hyaluronidase subcutaneously (SC) over 3-5 minutes on days 1, 8, 15, and 22 of cycles 1 and 2, on days 1 and 15 of cycles 3-6, then on day 1 of subsequent cycles. Patients also receive pomalidomide orally (PO) on days 1-21 of each cycle, dexamethasone PO or intravenously (IV) on days 1, 8, 15, and 22 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Treatment II (DKD): Patients are assigned to 1 of 2 options for carfilzomib. OPTION 1: Patients receive daratumumab-hyaluronidase SC over 3-5 minutes carfilzomib IV on days 1, 2, 8, 9, 15, and 16 of each cycle, and dexamethasone PO or IV on days 1, 2, 8, 9, 15, and 16 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. OPTION 2: Patients receive daratumumab-hyaluronidase SC over 3-5 minutes on days 1, 8, 15, and 22 of cycles 1 and 2, on days 1 and 15 of cycles 3-6 and on day 1 of subsequent cycles, carfilzomib IV on days 1, 8, and 15 of each cycle, and dexamethasone PO or IV on days 1, 8, 15, and 22 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. ARM B: Patients receive daratumumab-hyaluronidase SC over 3-5 minutes on days 1, 8, 15, and 22 of cycles 1 and 2, on days 1 and 15 of cycles 3-6 and on day 1 of subsequent cycles. Patients also receive teclistamab SC on day 2, 4, 8, 15 and 22 of cycle 1, on days 1, 8, 15, and 22 of cycle 2, on days 1 and 15 of cycles 3-6 and then on day 1 of subsequent cycles. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo urine and blood sample collection, bone marrow biopsy, and fludeoxyglucose F-18 (FDG) positron emission tomography (PET)/computed tomography (CT) throughout the study. After completion of study treatment, patients are followed up every 3 months for up to year 2, every 6 months up to year 5 then yearly for up to 10 years from randomization.

Conditions

• Recurrent Multiple Myeloma
• Refractory Multiple Myeloma

Interventions

Type	Name	Description
PROCEDURE	Biospecimen Collection	Undergo urine and blood sample collection
PROCEDURE	Bone Marrow Biopsy	Undergo bone marrow biopsy
DRUG	Carfilzomib	Given IV
PROCEDURE	Computed Tomography	Undergo FDG PET/CT
DRUG	Daratumumab and Recombinant Human Hyaluronidase	Given SC
DRUG	Dexamethasone	Given PO or IV
PROCEDURE	FDG-Positron Emission Tomography	Undergo FDG PET/CT
DRUG	Pomalidomide	Given PO
DRUG	Teclistamab	Given SC

Timeline

• Start date: 2026-04-29
• Primary completion: 2028-02-28
• Completion: 2028-02-28
• First posted: 2025-04-29
• Last updated: 2026-04-13

Regulatory

• FDA-regulated drug study