A Study of Different Sequences of Cilta-cel, Talquetamab in Combination With Daratumumab and Teclistamab in Combination With Daratumumab Following Induction With Daratumumab, Bortezomib, Lenalidomide and Dexamethasone in Participants With Standard-risk Newly Diagnosed Multiple Myeloma
Cilta-cel: Cilta-cel infusion will be administered intravenously.
Talquetamab: Talquetamab will be administered subcutaneously.
Daratumumab: Daratumumab will be administered subcutaneously as a part of DVRd induction and Tal-D or Tec-D consolidation.
Teclistamab: Teclistamab will be administered subcutaneously.
Bortezomib: Bortezomib will be administered subcutaneously as a part of induction.
Lenalidomide: Lenalidomide will be administered orally as a part of induction.
Dexamethasone: Dexamethasone will be administered orally as a part of induction.
Cyclophosphamide: Cyclophosphamide will be administered intravenously as a part of conditioning regimen.
Fludarabine: Fludarabine will be administered intravenously as a part of conditioning regimen.
Study summary
The purpose of this study is to evaluate the rate of response (how effectively treatment is working) with signs of potential cure at 5 years after the start of induction treatment. This is defined as a composite of sustained (at least 2 years) minimal residual disease (MRD) negativity with complete response/stringent complete response (CR/sCR) and a positron emission tomography/computed tomography (PET/CT) scan that does not show any signs of cancer at 5 years. MRD negativity and CR/sCR is defined as no detectable signs of remaining cancer cells after the treatment. This study will also characterize how well the treatments administered work in the study through progression-free survival (PFS). PFS is defined as the length of time during and after the treatment of a disease, that a participant lives with the disease, but it does not get worse.
Eligibility
Sex
ALL
Min age
18 Years
Max age
70 Years
Healthy volunteers
No
Inclusion Criteria:
* Participants with documented new diagnosis of multiple myeloma (MM) according to international myeloma working group (IMWG) diagnostic criteria and with no prior myeloma-directed therapy
* Participants must have standard-risk MM (stage I and II) based on revised International Staging System (R-ISS)
* Participants must be considered fit (score equals to \[=\] 0) or intermediate-fit (score=1) according to IMWG Frailty Index assessment (based on the Charlson Comorbidity Index, the Katz Activity of Daily Living and the Lawson Instrumental Activities of Daily Living)
* Measurable disease defined as: Serum monoclonal paraprotein (M-protein) level greater than or equal to (\>=) 1.0 gram per deciliter (g/dL) (\>=10 gram per liter \[g/L\] for institutions using alternative units) or urine M-protein level \>= 200 milligrams per 24 hours (mg/24 hours); Light chain MM without measurable disease in the serum or the urine: Serum immunoglobulin free light chain \>=10 milligrams per deciliter (mg/dL) (\>=100 mg/L for institutions using alternative units) and abnormal serum immunoglobulin kappa lambda free light chain ratio
* Eastern Cooperative Oncology Group (ECOG) performance status grade of 0 or 1
Exclusion Criteria:
* Any ongoing myelodysplastic syndrome or B-cell malignancy (other than MM). Any history of malignancy, other than MM, which is considered at high risk of recurrence requiring systemic therapy
* Peripheral neuropathy or neuropathic pain of Grade \>= 2, as defined by National Cancer Institute (NCI)-Common Terminology Criteria for Adverse Events (CTCAE) version 5.0
* Known active or prior history of central nervous system (CNS) involvement or exhibits clinical signs of meningeal involvement of MM
* Stroke or seizure within 6 months of signing the informed consent form (ICF)
* Plasma cell leukemia at the time of diagnosis or any time thereafter through apheresis (\>= 5 percent \[%\] circulating plasma cells in peripheral blood smears), Waldenstrom macroglobulinemia, polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes(POEMS) syndrome, or primary amyloid light chain amyloidosis with associated organ dysfunction
* Presence of high-risk disease features: (a) Cytogenetic high risk lesions by MM fluorescence in situ hybridization (FISH) including deletion 17p (del\[17p\])/, t(4;14), t(14;16), amplification 1q (amp\[1q21\]) (\>= 4 copies); (b) Presence of 1 or more extramedullary plasmacytomas
* Seropositive for human immunodeficiency virus (HIV)
Primary outcome measure(s)
Rate of Response with Curative Potential — Up to 5 years Rate of Response with curative potential is defined as the percentage of participants with a composite of durable (at least 2 years) minimal residual disease (MRD) (10\^-5) negativity with complete response/stringent complete response (CR/sCR) by serology and negative positron emission tomography/computed tomography (PET/CT) imaging at 5-years after start of induction therapy. This includes: negative imaging at 5-year landmark time; MRD-negative status (at 10\^-5) in 2 bone marrow examinations that are a minimum of 2 years apart; response of CR or better per the International Myeloma Working Group (IMWG) criteria; no examination showing MRD-positive status or relapse from CR in between assessments.
Progression Free Survival (PFS) Rate at 3-Year — At 3-year PFS is defined as the time from the date of randomization to either progressive disease (PD), according to the IMWG response criteria, or death, whichever occurs first.
PFS Rate at 5-Year — At 5-year PFS is defined as the time from the date of randomization to either PD, according to the IMWG response criteria, or death, whichever occurs first.
Trial sites (16)
Facility
City
Region
Status
City of Hope
Duarte
California
University of California San Francisco
San Francisco
California
University of Iowa Hospital and Clinics
Iowa City
Iowa
Memorial Sloan Kettering Cancer Center
New York
New York
Levine Cancer Institute
Charlotte
North Carolina
Peter MacCallum Cancer Centre
Melbourne
Australia
The Alfred Hospital
Melbourne
Australia
IDOR - Regional Bahia
Salvador
Brazil
Fundacao Antonio Prudente A C Camargo Cancer Center
São Paulo
Brazil
Sociedade Beneficente Israelita Brasileira Hospital Albert Einstein
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
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