Relapsed Refractory Multiple Myeloma
Conditions
Keywords
BCMA, CAR-T, CD19
Brief summary
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.
Interventions
BIOLOGICALAZD0120
CAR-T Cells
DRUGDaratumumab
Daratumumab
DRUGCarfilzomib
Carfilzomib
DRUGDexamethasone
Dexamethasone
DRUGBortezomib
Bortezomib
DRUGPomalidomide
Pomalidomides
Sponsors
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Open-label
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Secondary
| Measure | Time frame |
|---|---|
| To further demonstrate the effectiveness of AZD0120 relative to standard therapy (DKd, DPd, PVd, or Kd) by assessment of CRR in participants with RRMM. | 2 years |
| To further demonstrate the effectiveness of AZD0120 relative to standard therapy (DKd, DPd, PVd, or Kd) by assessment of ORR in participants with RRMM. | 2 years |
| To further demonstrate the effectiveness of AZD0120 relative to standard therapy (DKd, DPd, PVd, or Kd) by assessment of OS in participants with RRMM. | 5 years |
Countries
Australia, Brazil, Canada, France, Germany, Italy, Japan, Norway, Poland, South Korea, Spain, Taiwan, United Kingdom, United States
Contacts
CONTACTAstraZeneca Clinical Study Information Center
Outcome results
None listed