C1071006 - An open-label, 2-arm, multicenter, randomized phase 3 study to evaluate the efficacy and safety of Elranatamab (PF-06863135) + Daratumumab + Lenalidomide versus Daratumumab + Lenalidomide + Dexamethasone in transplant-ineligible participants with newly-diagnosed multiple myeloma (MAGNETISMM-6)

Studio Clinico

Patologia: Mieloma

Osservazionale-Sperimentale: Sperimentale

Monocentrico-Multicentrico: Multicentrico

Randomizzato: Sì

Fase di studio: III

Linee di trattamento: Non applicabile

Criteri di inclusione: 

- Diagnosis of multiple myeloma (MM) as defined by IMWG criteria (Rajkumar et al., 2014)
- Measurable disease based on IMWG criteria as defined by at least 1 of the following:
    - Serum M-protein ≥0.5 g/dL;
    - Urinary M-protein excretion ≥200 mg/24 hours;
    - Involved FLC ≥10 mg/dL (≥100 mg/L) AND abnormal serum immunoglobulin kappa to lambda FLC ratio (<0.26 or >1.65).
- Part 1: Participants with relapsed/refractory multiple myeloma (RRMM) who have received 1-2 prior lines of therapy including at least one immunomodulatory drug and one proteasome inhibitor: or participants with newly-diagnosed multiple myeloma (NDMM) that are transplant-ineligible as defined by age ≥65 years or transplant-ineligible as defined by age <65 years with comorbidities impacting the possibility of transplant.
- Part 2: participants with newly-diagnosed multiple myeloma that are transplant-ineligible as defined by age ≥65 years or transplant-ineligible as defined by age <65 years with comorbidities impacting the possibility of transplant
- ECOG performance status ≤2.
- Not pregnant and willing to use contraception
- For participants with RRMM: Resolved acute effects of any prior therapy to baseline severity or CTCAE Grade ≤1.

Criteri di esclusione: 

- Smoldering Multiple Myeloma.
- Monoclonal gammopathy of undetermined significance.
- Waldenströms Macroglobulinemia
- Plasma cell leukemia.
- Active, uncontrolled bacterial, fungal, or viral infection, including (but not limited to) COVID-19/SARS-CoV-2, HBV, HCV, and known HIV or AIDS-related illness.
- Any other active malignancy within 3 years prior to enrollment, except for adequately treated basal cell or squamous cell skin cancer, carcinoma in situ, or Stage 0/1 with minimal risk of recurrence per investigator.
- For participants with RRMM: Previous treatment with a BCMA-directed therapy or anti-CD38-directed therapy within 6 months preceding the first dose of study intervention in this study. Stem cell transplant ≤3 months prior to first dose of study intervention or active GVHD.
- For participants with NDMM: Previous systemic treatment for MM except for a short course of corticosteroids (ie, up to 4 days of 40 mg dexamethasone or equivalent before the first dose of study intervention).
- Live attenuated vaccine administered within 4 weeks of the first dose of study intervention.
- Administration of investigational product (eg, drug or vaccine) concurrent with study intervention or within 30 days (or as determined by the local requirement) preceding the first dose of study intervention used in this study.

Schema di trattamento: 

Experimental: Part 1, Dose Level 1: Elranatamab + Daratumumab + Lenalidomide
Interventions:
Drug: Elranatamab
Drug: Daratumumab
Drug: Lenalidomide
Experimental: Part 1, Multiple Dose Levels, Elranatamab + Daratumumab + Lenalidomide
Interventions:
Drug: Elranatamab
Drug: Daratumumab
Drug: Lenalidomide
Experimental: Part 2 Randomized Arm A: Elranatamab + Daratumumab + Lenalidomide
Interventions:
Drug: Elranatamab
Drug: Daratumumab
Drug: Lenalidomide
Active Comparator: Part 2 Randomized Arm B: Daratumumab + Lenalidomide + Dexamethasone
Interventions:
Drug: Daratumumab
Drug: Lenalidomide
Drug: Dexamethasone.

Trattamento sperimentale: 

Part 1, Dose Level 1: Elranatamab + Daratumumab + Lenalidomide
Part 1, Multiple Dose Levels, Elranatamab + Daratumumab + Lenalidomide
Part 2 Randomized Arm A: Elranatamab + Daratumumab + Lenalidomide.

Trattamento di controllo: 

Part 2 Randomized Arm B: Daratumumab + Lenalidomide + Dexamethasone

Obiettivi primari dello studio: 

Part 1 Dose Limiting Toxicity [Time Frame: From the first dose of elranatamab until 28 days (+/- visit window) from the first administration of the EDR combination]
Part 2: Progression free survival by blinded independent central review [Time Frame: From randomization up to 73 months.]
Part 2: Sustained minimal residual disease negativity rate [Time Frame: For at least 12 months after date of initial MRD-negative status].

Data di inizio dell'arruolamento: 08.08.2023

Data di fine dell'arruolamento: 27.08.2025

Centri partecipanti

Nord Italia

Centro Italia

Sud Italia e isole

Informazioni Generali

Protocollo

Numero di iscrizione a registro: 2021-000803-20

Data di inserimento: 02.11.2023

Promotore

Pfizer

CRO

Parexel

Principal Investigator ITALIA

Riferimento: Dr. Info non disponibile

Telefono: 00000

Email: nd@nd.it

Localita: nd