A Phase III, Multicentre Study to Evaluate Consolidation Treatment With AZD0120 Compared With ASCT, in Participants With Newly Diagnosed Multiple Myeloma Who Are Transplant Eligible (DURGA-6).

AstraZeneca

Status and phase: Begins enrollment this month; Phase 3

Conditions: Newly Diagnosed Multiple Myeloma (NDMM)

Treatments: Drug: Melphalan (part of ASCT); Biological: AZD0120; Drug: Lenalidomide; Drug: Cyclophosphamide; Drug: Fludarabine

Study type: Interventional

Funder types: Industry

Identifiers

NCT07735637

AZD0120 (Other Identifier)

D8316C00001

Details and patient eligibility

About

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.

Enrollment: 750 estimated patients

Sex: All

Ages: 18 to 130 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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750 participants in 2 patient groups

Arm A: AZD0120

Experimental group

Description:

AZD0120 is an autologous chimeric antigen receptor T-cell (CAR-T) therapy.

Treatment:

Drug: Fludarabine

Drug: Cyclophosphamide

Drug: Lenalidomide

Biological: AZD0120

Arm B: Autologous Stem Cell Transplant (ASCT)

Active Comparator group

Description:

ASCT: High-dose melphalan followed by autologous stem cell rescue

Treatment:

Drug: Lenalidomide

Drug: Melphalan (part of ASCT)