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Purpose

This is a randomised, multicentre, controlled, open-label, Phase III global study comparing the efficacy and safety of standard induction regimens (IsaVRd and DRd) followed by AZD0120 versus standard induction regimens followed by continuous therapy (IsaRd and DRd) in participants with newly diagnosed multiple myeloma (NDMM) who are ineligible for autologous stem cell transplant (ASCT) as initial therapy.

Condition

Eligibility

Eligible Ages
Over 18 Years
Eligible Sex
All
Accepts Healthy Volunteers
No

Inclusion Criteria

  1. Participants must be 18 years or older, at the time of signing the ICF. 2. Participant must have documented diagnosis of MM according to the IMWG diagnostic criteria. 3. Participant must have one or more of the following measurable disease criteria: (a) Serum M-protein level ≥1.0 g/dL, (b) Urine M-protein level ≥ 200 mg/24 h, (c)Serum immunoglobulin FLC ≥ 10 mg/dL (100 mg/L) and abnormal serum immunoglobulin kappa lambda FLC ratio. 4. Participant must be deemed ineligible for ASCT while also having adequate organ function for CAR-T cell treatment. 5. Participant is a candidate to receive at least one of the regimens (IsaVRd or DRd) as determined by the Investigator. 6. ECOG performance status Grade of 0 to 2. 7. Participant must have adequate organ and bone marrow function.

Exclusion Criteria

  1. Participant has active or prior CNS or meningeal involvement of MM. 2. Participant has primary amyloidosis, active plasma cell leukemia (≥5% circulating plasma cells), Waldenström macroglobulinemia, or POEMS syndrome. 3. Participant has significant neurological or psychiatric condition posing risk or impairing evaluation. 4. Participant has any other significant medical condition that increases unacceptable risk, interferes with therapy delivery, or confounds evaluation. 5. Participant has a history of a prior non-haematologic malignancy unless the participant has been disease-free with no evidence of recurrence for ≥ 2 years. 6. Participant has a history of haematologic malignancies, other than MM, regardless of remission status. 7. Participant is positive for any of the following: 1. HIV: Known to be seropositive for HIV (including any history of HIV). 2. Chronic or active hepatitis B. 3. Active hepatitis C: Hepatitis C infection. 4. Additional local requirements for the testing for infectious diseases and exclusions of applicable participants should be followed per local regulations. 8. Participant has clinically significant cardiovascular disease. 9. Participant has COPD with an FEV1 < 50% of predicted normal. 10. Additional exclusion for participants who are planned to receive IsaVRd as induction: Participant has peripheral neuropathy Grade 4, Grade 3, Grade 2, or Grade 1 with pain.

Study Design

Phase
Phase 3
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Intervention Model Description
This is a randomised, multicentre, controlled, open-label, Phase III global study comparing the efficacy and safety of AZD0120 versus standard regimens (IsaVRd and DRd) in participants with NDMM who are ineligible to receive ASCT as initial therapy.
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Arm A: Investigational Arm 		Arm A is the sequence of induction with IsaVRd or DRd, apheresis, optional bridging therapy, lymphodepletion (cyclophosphamide and fludarabine), and AZD0120.
  • Biological: AZD0120
    AZD0120, is a BCMA/CD19 dual CAR T-cell product, which is administered intravenously.
  • Biological: Daratumumab
    Induction, optional bridging and continuous therapy.
  • Drug: Dexamethasone
    Induction, optional bridging and continuous therapy.
  • Biological: Isatuximab
    Induction, optional bridging and continuous therapy.
  • Drug: Lenalidomide
    Induction, optional bridging and continuous therapy.
  • Drug: Bortezomib
    Induction therapy.
  • Drug: Cyclophosphamide
    Lymphodepletion
  • Drug: Fludarabine
    Lymphodepletion
Active Comparator
Arm B: Control Arm 		Arm B is the standard therapy induction with IsaVRd or DRd, followed by continuous IsaRd or DRd until disease progression or intolerable toxicity.
  • Biological: Daratumumab
    Induction, optional bridging and continuous therapy.
  • Drug: Dexamethasone
    Induction, optional bridging and continuous therapy.
  • Biological: Isatuximab
    Induction, optional bridging and continuous therapy.
  • Drug: Lenalidomide
    Induction, optional bridging and continuous therapy.
  • Drug: Bortezomib
    Induction therapy.

More Details

Status
Recruiting
Sponsor
AstraZeneca

Study Contact

AstraZeneca Clinical Study Information Center
1-877-240-9479
information.center@astrazeneca.com

Detailed Description

The primary objective is to demonstrate the superiority of IsaVRd or DRd induction followed by a single administration of AZD0120 compared to IsaVRd or DRd induction followed by continuous IsaRd or DRd in terms of progression-free survival (PFS) according to IMWG 2016 criteria, and as assessed by Blinded Independent Central Review (BICR) and miminal residual disease (MRD) negative complete response (CR) rate at 9 months post-randomisation in participants with NDMM who are ineligible to receive ASCT as initial therapy.

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.