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

ConditionsRecurrent Multiple Myeloma Refractory Multiple Myeloma

Trial statusRecruiting

Trial phasePhase 2

Trial typeInterventional

Biological sexAll

Age18+

SponsorNational Cancer Institute (NCI)

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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

Disqualifiers

None

Trial design

Design model

Parallel

Treatments tested in this trial

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

Treatment groups

80 Participants

are divided into 4 treatment groups

Group A: Arm A Treatment I (DPd)Active comparator 7 interventions

Group B: Arm A Treatment II Option 1 (DKd)Active comparator 7 interventions

Group C: Arm A Treatment II Option 2 (DKd)Active comparator 7 interventions

Group D: Arm B (daratumumab, teclistamab)Experimental treatment 6 interventions

Trial outcomes

Primary outcomes

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.

Time frame

After 6 cycles of treatment (cycle length = 28 days), assessed at 6 months

Secondary outcomes

Incidence of adverse events (AEs)

Will be graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) and classified by Medical Dictionary for Regulatory Activities (MedDRA) system organ class. Maximum grade toxicity by AE type will be tabulated. Summaries (count and percentages) will be reported by AE type by arm.

Time frame

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

Will be graded according to the NCI CTCAE and classified by MedDRA system organ class. Maximum grade toxicity by AE type will be tabulated. Summaries (count and percentages) will be reported by AE type by arm. Rates of maximum grade 3 or higher (including grade 5) non-hematologic, hematologic and overall toxicity will be calculated along with 90% CIs. AEs will be further analyzed by arm in subsets of serious AEs per protocol, lethal AEs and treatment-emergent AEs status.

Time frame

Up to 6 cycles (cycle length = 28 days) and overall assessed up to 10 years

Progression-free survival (PFS)

PFS will be estimated in the treated population using the Kaplan-Meier method and compared between arms using the stratified log-rank test. Stratified cox proportional hazards (PH) regression will be used to produce the treatment hazard ratio (HR) along with the 90% CI, provided PH assumption is valid. Sensitivity analyses excluding untreated patients will be conducted.

Time frame

From randomization until the earlier of progression or death due to any cause, assessed up to 10 years

Overall survival (OS)

OS will be estimated in the treated population using the Kaplan-Meier method and compared between arms using the stratified log-rank test. Stratified cox PH regression will be used to produce the treatment HR along with the 90% CI, provided PH assumption is valid. Sensitivity analyses excluding untreated patients will be conducted.

Time frame

From randomization to death due to any cause, assessed up to 10 years

Other outcomes

Event-free survival

Time frame

From randomization until the earlier of non-protocol therapy, progression, or death due to any cause, assessed up to 10 years

Time to progression

Time frame

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

Time frame

From randomization to treatment end, or censored at the date of last treatment, assessed up to 10 years

Cumulative dose intensity

Will be defined as the sum of all doses taken across all cycles. Will be characterized using descriptive statistics.

Time frame

Up to 24 months (cycle length = 28 days)

Locations23

Select a site below to view it on the map.

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

National Cancer Institute (NCI)

Lead sponsor

Source ClinicalTrials.gov

Apply now