A Study Comparing AZD0120, a Dual-targeted CAR-T Against B-cell Maturation Antigen (BCMA) and CD19, Versus Standard Regimens in Participants With Relapsed Refractory Multiple Myeloma (DURGA-4)
This is a randomised, multicentre, controlled, open-label, Phase III global study comparing the efficacy and safety of AZD0120 versus standard regimens (DKd \[daratumumab, carfilzomib, and dexamethasone\], DPd \[daratumumab, pomalidomide, and dexamethasone\], PVd \[pomalidomide, bortezomib and dexamethasone\], or Kd \[carfilzomib and dexamethasone\]) in participants with RRMM.
Eligibility
Sex
ALL
Min age
18 Years
Max age
—
Healthy volunteers
No
Inclusion Criteria:
* Age ≥ 18 years
* Documented diagnosis of multiple myeloma according to the IMWG diagnostic criteria
* Documented evidence of measurable disease:
1. Serum M-protein level ≥ 1 g/dL
2. Urine M-protein level ≥ 200 mg/24h
3. Serum immunoglobulin free light chain ≥ 10 mg/dL (100 mg/L) and abnormal serum immunoglobulin kappa lambda free light chain ratio
* Documented evidence of PD by IMWG 2016 criteria based on investigator's determination during or after the most recent line of therapy. Participants with only 1 prior line of therapy must have progressed within 47 months of a stem cell transplant, or if not transplanted, then within 42 months of starting initial therapy
* Received 1 to 3 lines of prior therapy including an IMiD and either a PI or a CD38 antibody. Participant must have undergone at least 2 complete cycles of treatment for each line of therapy, unless PD was the best response to the line of therapy
* Eligible to receive at least one of the standard regimens (DKd, PVd, DPd, or Kd) as determined by the Investigator.
* ECOG performance status score of 0 to 1
* Adequate hematology and chemistry laboratory values:
1. Haemoglobin ≥ 8.0 g/dL
2. Absolute neutrophil count ≥ 1 × 10\^9/L (1000 per mm3)
3. Platelet count ≥ 75 × 10\^9/L (75000 per mm3) in participants with \< 50% of bone marrow nucleated cells are plasma cells or ≥ 50 × 10\^9/L (50000 per mm3) in participants with ≥ 50% of bone marrow nucleated cells are plasma cells
4. Absolute lymphocyte count ≥ 300/µL (0.3 × 109/L)
5. Total bilirubin ≤ 1.5 × ULN in the absence of Gilbert's syndrome or ≤ 3 × ULN if the participant has Gilbert's syndrome. AST and ALT≤ 3.0 × ULN. CrCl by Cockcroft and Gault method ≥ 30 mL/minute
Exclusion Criteria:
* Known active, or prior history of CNS involvement or exhibits clinical signs of meningeal involvement of MM.
* Primary amyloidosis, active plasma cell leukaemia, Waldenstrom macroglobulinemia or Polyneuropathy Organomegaly Endocrinopathy M-protein and Skin (POEMS) syndrome.
* Participants with primary refractory MM (failed to generate at least a minimal response to any prior therapy)
* Significant neurological or psychiatric condition
* Significant medical condition that places the participant at an unacceptable risk for treatment-related complications
* Previously received any prior BCMA-targeted treatment
* Previously received CAR-T or CAR-NK therapy directed at any target
* Previously received T-cell engager therapy directed at any target
* Previously received allogeneic stem cell transplantation at any time during prior therapy or received autologous stem cell transplantation within 12 weeks of randomization
Primary outcome measure(s)
To demonstrate the superiority of AZD0120 relative to standard therapy (DKd, DPd, PVd, or Kd) by assessment of PFS in participants with RRMM. — 3 years PFS: defined as time from randomisation until progression according to IMWG 2016 criteria as assessed by BICR, or death due to any cause, whichever occurs first.
To demonstrate the superiority of AZD0120 relative to standard therapy (DKd, DPd, PVd, or Kd) by assessment of MRD negativity rate at 9 months in participants with RRMM. — 2 years MRD negative CR rate at 9 months: defined as the proportion of participants with MRD negative status and have a response of CR or sCR (according to the IMWG 2016 criteria) at 9 months (± 3 months) from randomisation before initiation of subsequent anti-myeloma therapy.
Trial sites (143)
Facility
City
Region
Status
Research Site
Gilbert
Arizona
Not Yet Recruiting
Research Site
Phoenix
Arizona
Withdrawn
Research Site
Tucson
Arizona
Not Yet Recruiting
Research Site
La Jolla
California
Withdrawn
Research Site
Sacramento
California
Not Yet Recruiting
Research Site
Santa Monica
California
Not Yet Recruiting
Research Site
Denver
Colorado
Recruiting
Research Site
New Haven
Connecticut
Recruiting
Research Site
Washington D.C.
District of Columbia
Not Yet Recruiting
Research Site
Coral Gables
Florida
Withdrawn
Research Site
Tampa
Florida
Not Yet Recruiting
Research Site
Atlanta
Georgia
Recruiting
Research Site
Chicago
Illinois
Not Yet Recruiting
Research Site
Park Ridge
Illinois
Not Yet Recruiting
Research Site
Iowa City
Iowa
Withdrawn
Research Site
Kansas City
Kansas
Not Yet Recruiting
Research Site
Louisville
Kentucky
Recruiting
Research Site
Boston
Massachusetts
Not Yet Recruiting
Research Site
Boston
Massachusetts
Not Yet Recruiting
Research Site
Boston
Massachusetts
Withdrawn
Research Site
Detroit
Michigan
Withdrawn
Research Site
Detroit
Michigan
Withdrawn
Research Site
Rochester
Minnesota
Withdrawn
Research Site
Albany
New York
Not Yet Recruiting
Research Site
New York
New York
Withdrawn
Research Site
New York
New York
Recruiting
Research Site
New York
New York
Withdrawn
Research Site
New York
New York
Recruiting
Research Site
Rochester
New York
Withdrawn
Research Site
The Bronx
New York
Withdrawn
Research Site
Chapel Hill
North Carolina
Not Yet Recruiting
Research Site
Charlotte
North Carolina
Not Yet Recruiting
Research Site
Charlotte
North Carolina
Recruiting
Research Site
Winston-Salem
North Carolina
Recruiting
Research Site
Winston-Salem
North Carolina
Not Yet Recruiting
Research Site
Cincinnati
Ohio
Not Yet Recruiting
Research Site
Cleveland
Ohio
Not Yet Recruiting
Research Site
Portland
Oregon
Not Yet Recruiting
Research Site
Charleston
South Carolina
Withdrawn
Research Site
Nashville
Tennessee
Recruiting
+ 103 more sites — see the full list on the official registry below.
Official registry record
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
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