A Study of Daratumumab, Bortezomib, Lenalidomide and Dexamethasone (DVRd) Followed by Ciltacabtagene Autoleucel Versus Daratumumab, Bortezomib, Lenalidomide and Dexamethasone (DVRd) Followed by Autologous Stem Cell Transplant (ASCT) in Participants With Newly Diagnosed Multiple Myeloma

JRCT ID: jRCT2063220071

Registered date:25/11/2022

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: Newly Diagnosed Multiple Myeloma
• Date of first enrollment: 27/08/2024
• Target sample size: 50
• Countries of recruitment: Norway,Japan,Australia,Japan,Belgium,Japan,Canada,Japan,Czech,Japan,France,Japan,Germany,Japan,Greece,Japan,Israel,Japan,Italy,Japan,Netherlands,Japan,Spain,Japan,Switzerland,Japan,Sweden,Japan,UK,Japan,US,Japan
• Study type: Interventional

Intervention(s)

- Arm A (DVRd Induction + ASCT + DVRd Consolidation + Lenalidomide Maintenance)
Participants randomized to Arm A will receive four 28-day cycles of DVRd induction (Cycles 1-4), followed by stem cell harvest, high-dose melphalan, ASCT, and two 28-day cycles of DVRd consolidation (Cycles 5-6).
- Arm B (DVRd Induction + Cilta-cel + Lenalidomide Post-CAR-T Therapy)
Participants randomized to Arm B will undergo apheresis to acquire mononuclear cells before start of DVRd induction therapy. Cilta-cel will be generated from the participants T-cells selected from the apheresis product. After apheresis, participants will receive six 28-day cycles of DVRd induction (Cycles 1-6).

Outcome(s)

• Primary Outcome: The dual primary endpoints are PFS and sustained MRD-negative CR.

Secondary Outcome

- Overall response Rate: achieving a PR or better according to the IMWG response criteria.
- CR or better status: achieving a CR or sCR according to the IMWG response criteria.
- Overall MRD-negative CR: achieving MRD-negative CR, as determined by NGS with a sensitivity of at least 10^5 at any time after the date of randomization before initiation of subsequent antimyeloma therapy.
- Time to subsequent antimyeloma therapy: the time from the date of randomization to the start of subsequent antimyeloma therapy. Death due to PD without the start of any subsequent antimyeloma therapy will be considered an event. Participants who withdraw consent to study, are lost-to-follow-up, or die due to causes other than PD will be censored at the date of death or the date the participant was last known to be alive.
- PFS2: the time from the date of randomization to the date of event, defined as PD as assessed by investigator that starts after the next line of subsequent therapy, or death due to any cause, whichever occurs first. Those who are alive and for whom a second PD has not been observed are censored at the last date of follow up.
-OS: the time from the date of randomization to the date of death. If the participant is alive or the vial status is unknown, the data of the patient will be censored at the date the participant was last known to be alive.

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

- Participants with documented NDMM according to IMWG diagnostic criteria, for whom high-dose therapy and ASCT are part of the intended initial treatment plan.
- Measurable disease, as assessed by central laboratory, at screening as defined by any of the following:
a. Serum monoclonal paraprotein (M-protein) level >=1.0 g/dL or urine M-protein level >=200 mg/24 hours; or
b. Light chain MM without measurable disease in serum or urine: serum Ig free-light chain (FLC) >=10 mg/dL and abnormal serum Ig kappa lambda FLC ratio.
- ECOG performance status of grade 0 or 1
- Clinical laboratory values within prespecified range.

Exclude criteria

- Prior treatment with CAR-T therapy directed at any target.
- Any prior BCMA target therapy.
- Any prior therapy for MM or smoldering myeloma other than a short course of corticosteroids
- Received a strong cytochrome P450 (CYP)3A4 inducer within 5 half-lives prior to randomization
- Received or plans to receive any live, attenuated vaccine (except for COVID-19 vaccines) within 4 weeks prior to randomization.
- Known active, or prior history of central nervous system (CNS) involvement or clinical signs of meningeal involvement of MM
- Stroke or seizure within 6 months of signing Informed Consent Form (ICF)

Related Information

• Primary Sponsor: Gazzera Giulia
• Secondary ID(s): NCT05257083,2021-003284-10