Newly Diagnosed Multiple Myeloma (NDMM)
Conditions
Keywords
Multiple Myeloma, NDMM, AZD0120, cell therapy, CAR-T, DURGA-6, BCMA, CD19, transplant eligible
Brief summary
The purpose of this study is to measure the efficacy of AZD0120 compared with ASCT in terms of progression-free survival (PFS) according to the International Myeloma Working Group (IMWG) criteria 2016, and MRD negative complete response (CR) rate at 9 months as assessed by Blinded Independent Central Review (BICR), in participants with TE NDMM. Study details include: * The study duration is estimated to be up to 13 years from the date the first participant is randomised. * For participants in Arm A (AZD0120), the total duration of participant follow-up will be 15 years (including a Long Term Follow-up study) after the last participant has received the AZD0120 infusion. * The treatment duration will be:- Arm A (AZD0120): lymphodepletion over 3 days, a single-day infusion of AZD0120, followed by a maximum of 2 years lenalidomide monotherapy maintenance treatment. * Arm B (ASCT): conditioning therapy over 24 to 48 hours, ASCT, followed by a maximum of 2 years lenalidomide monotherapy maintenance treatment. Disclosure Statement: This is an open-label, randomised study with 2 treatment arms.
Interventions
BIOLOGICALAZD0120
Arm A: AZD0120 - autologous BCMA/CD19 dual-targeting CAR-T cells. Participants will receive lymphodepletion conditioning (cyclophosphamide and fludarabine) followed by AZD0120 CAR-T cell infusion.
DRUGCyclophosphamide
Arm A: Cyclophosphamide will be given intravenously as lymphodepletion conditioning.
DRUGFludarabine
Arm A: Fludarabine will be given intravenously as lymphodepletion conditioning.
DRUGMelphalan (part of ASCT)
Arm B - Autologous stem cell transplant: High-dose melphalan will be given over 1-2 days, followed by autologous stem cell rescue.
DRUGLenalidomide
Arm A and Arm B: Lenalidomide maintenance treatment will be started in both Arm A and Arm B after AZD0120 therapy or ASCT, respectively. Lenalidomide maintenance on study will be continued up to 2 years.
Sponsors
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Masking description
None (open label)
Eligibility
Sex/Gender
ALL
Age
18 Years to 130 Years
Healthy volunteers
No
Inclusion criteria
* ≥18 years of age. * Documented diagnosis of NDMM according to IMWG diagnostic criteria. * Documented measurable disease at diagnosis (serum M-protein ≥ 1.0 g/dL, urine M-protein 200 mg/24 hour, or serum Ig FLC 10 mg/dL (100 mg/L) and abnormal serum Ig kappa lambda FLC ratio) * Must have completed 4 to 6 cycles of induction therapy with any of the following approved regimens: anti-CD38+VRd, DVTd, DRd or VRd * Participant must have at least SD or better per IMWG response criteria (2016) after completion of induction, and prior to randomisation. * ECOG performance status score of 0 or 1. * Eligible for treatment with high-dose melphalan (200 mg/m²) followed by ASCT. * Adequate organ and bone marrow function.
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 (at diagnosis and/or at time of screening), Waldenstrom macroglobulinemia or POEMS syndrome. * Significant neurological or psychiatric condition * Significant medical condition that places the participant at an unacceptable risk for treatment-related complications * Participants who required the introduction of an additional agent therapy due to inadequate response. * Prior T-cell engager therapy directed at any target. * Prior CAR-T and/or CAR-NK cell therapy directed at any target for any indications * Prior any therapy that is targeted to BCMA and CD19.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-Free Survival (PFS) | Up to approximately 13 years. | PFS is defined as time from randomisation until progression as assessed by Blinded Independent Central Review, or death due to any cause, whichever occurs first. |
| Minimal Residual Disease (MRD) negative Complete Response Rate (CRR) | Up to approximately 13 years. | MRD negative CRR is defined as the proportion of participants with a MRD negative status and who have a response of CR or a stringent CR. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Secondary: Overall Survival (OS) | Up to approximately 13 years. | OS is defined as time from randomisation until date of death due to any cause. |
| Secondary: Complete Response Rate (CRR) | Up to approximately 13 years. | CRR (CR or stringent CR rate) is defined as the proportion of participants who achieved CR or better and as assessed by Blinded Independent Central Review. |
| Secondary: Overall Response Rate (ORR) | Up to approximately 13 years. | ORR is defined as the proportion of participants with a response (complete, partial or very good partial response) as assessed by Blinded Independent Central Review. |
| Secondary: Duration of Response (DoR) | Up to approximately 13 years. | DoR is defined as the time from first response to progression or death |
| Other secondary: Time to Response (TTR) | Up to approximately 13 years. | TTR is defined as the time from randomisation to first response |
| Safety - Adverse Events | Up to approximately 13 years. | To evaluate safety in terms of the number of participants experiencing an Adverse Event. |
Countries
Australia, Brazil, Canada, Denmark, France, Germany, Italy, Norway, Poland, Singapore, South Korea, Spain, Taiwan, United Kingdom, United States
Contacts
CONTACTAstraZeneca Clinical Study Information Center
Outcome results
None listed