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)
3 other identifiers
interventional
80
0 countries
N/A
Brief 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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_2
Started Aug 2026
Shorter than P25 for phase_2
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
April 26, 2025
CompletedFirst Posted
Study publicly available on registry
April 29, 2025
CompletedStudy Start
First participant enrolled
August 26, 2026
ExpectedPrimary Completion
Last participant's last visit for primary outcome
February 28, 2028
Study Completion
Last participant's last visit for all outcomes
February 28, 2028
May 13, 2026
May 1, 2026
1.5 years
April 26, 2025
May 12, 2026
Conditions
Outcome Measures
Primary Outcomes (1)
Minimal residual disease (MRD) negativity
Will be determined by the Adaptive Biotechnologies clonoSEQ assay result. Analysis will be performed using Cochran-Mantel-Haenszel (CMH) test, stratified on prior anti-CD38 antibody therapy and investigator's choice of therapy if assigned to Arm A. MRD-negative status requires both MRD negativity and achievement of complete response. Will be summarized using descriptive statistics by treatment arm with two-sided exact binomial 80% confidence intervals (CI), Clopper-Pearson. The corresponding CMH odds ratio (OR) estimate with an 80% CI, and p-value will be reported. Logistic regression will be used to assess the treatment effect within subgroups including but not limited to age 70 status, prior anti-CD38 antibody therapy and high-risk by fluorescence in situ hybridization status.
After 6 cycles of treatment (cycle length = 28 days), assessed at 6 months
Secondary Outcomes (5)
Incidence of adverse events (AEs)
Up to 6 cycles (cycle length = 28 days) and overall assessed up to 10 years
Incidence of grade 3 or higher hematologic and/or non-hematologic AEs
Up to 6 cycles (cycle length = 28 days) and overall assessed up to 10 years
Progression-free survival (PFS)
From randomization until the earlier of progression or death due to any cause, assessed up to 10 years
Overall survival (OS)
From randomization to death due to any cause, assessed up to 10 years
Response rates
After 6 cycles of treatment (cycle length = 28 days) and overall, assessed up to 10 years
Other Outcomes (12)
Event-free survival
From randomization until the earlier of non-protocol therapy, progression, or death due to any cause, assessed up to 10 years
Time to progression
From randomization to time of documented progression or censored at date of last disease evaluation if alive or death not due to disease progression, assessed up to 10 years
Duration of treatment
From randomization to treatment end, or censored at the date of last treatment, assessed up to 10 years
- +9 more other outcomes
Study Arms (4)
Arm A Treatment I (DPd)
ACTIVE COMPARATORPatients 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, then on day 1 of subsequent cycles. Patients also receive pomalidomide PO on days 1-21 of each cycle, 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. Additionally, patients undergo urine and blood sample collection, bone marrow biopsy, and FDG PET/CT throughout the study.
Arm A Treatment II Option 1 (DKd)
ACTIVE COMPARATORPatients 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. Additionally, patients undergo urine and blood sample collection, bone marrow biopsy, and FDG PET/CT throughout the study.
Arm A Treatment II Option 2 (DKd)
ACTIVE COMPARATORPatients 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. Additionally, patients undergo urine and blood sample collection, bone marrow biopsy, and FDG PET/CT throughout the study.
Arm B (daratumumab, teclistamab)
EXPERIMENTALPatients 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 FDG PET/CT throughout the study.
Interventions
Undergo FDG PET/CT
Given PO
Given SC
Given SC
Undergo urine and blood sample collection
Undergo bone marrow biopsy
Given IV
Given PO or IV
Undergo FDG PET/CT
Eligibility Criteria
You may qualify if:
- Patient must be ≥ 18 years of age
- Patient must have an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0-2 (PS 3 allowed if secondary to pain)
- Patient must have an identifiable dominant sequence (clonotype) established based on Adaptive Biotechnologies clonoSEQ® assay
- Patient must have received only one prior line of therapy
- One prior line of systemic therapy is defined as 1 or more cycles of single agent or combination therapy, as well as a series of treatment regimens administered in a sequential manner (e.g., lenalidomide, bortezomib and dexamethasone induction therapy for 4 cycles followed by autologous stem cell transplantation and then lenalidomide +/- proteasome inhibitor or anti-CD38 monoclonal antibody (mAb) maintenance therapy would be considered 1 line of prior therapy)
- NOTE: Autologous stem cell transplant is allowed provided the stem cell infusion was \> 90 days prior to randomization. Allogeneic stem cell transplantation (SCT) patients are ineligible
- Patient must be diagnosed with relapsed or refractory (RR) multiple myeloma, as defined by disease progression, either an increase in serum or urine M protein of any level, or other evidence of progression biochemical or clinical as specified in the IMWG progression criteria (including disease which becomes non-responsive or progressive on therapy or within 60 days of the last treatment in patients who had achieved a partial response or better on prior therapy)
- Patient must be daratumumab-hyaluronidase (or isatuximab) naïve or daratumumab-hyaluronidase (or isatuximab) sensitive and \> 180 days from their last dose of daratumumab-hyaluronidase (or isatuximab) at the time of randomization
- Patient must have high-risk multiple myeloma (HR-MM) as defined by one of the following either at diagnosis or at refractory status or at first relapse:
- Evidence of deletion 17p by fluorescence in situ hybridization (FISH) testing on bone marrow
- Evidence of t(4;14) by FISH testing on bone marrow
- Evidence of t(14;16) by FISH testing on bone marrow
- Evidence of t(14;20) by FISH testing on bone marrow
- Evidence of chromosome 1 abnormalities either gain/amp 1q or deletion 1p by FISH testing on bone marrow OR
- Evidence of non-hyperdiploid karyotype OR
- +37 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Muhamed Baljevic
ECOG-ACRIN Cancer Research Group
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- NIH
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
April 26, 2025
First Posted
April 29, 2025
Study Start (Estimated)
August 26, 2026
Primary Completion (Estimated)
February 28, 2028
Study Completion (Estimated)
February 28, 2028
Last Updated
May 13, 2026
Record last verified: 2026-05
Data Sharing
- IPD Sharing
- Will share
NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page.