A Study to Evaluate Efficacy and Safety of Ciltacabtagene Autoleucel

Official title

A Phase 2 Multicohort Trial to Further Characterize the Efficacy and Safety of Ciltacabtagene Autoleucel

Overview

The purpose of this study is to evaluate how well (efficacy) cilta-cel works when given with a fludarabine-free lymphodepletion regimen (a process of reducing the number of lymphocytes, a type of white blood cell in the body, typically through chemotherapy), or an alternative administration of cilta-cel infusion following a cyclophosphamide and fludarabine lymphodepletion regimen.

Interventions

• Drug Cilta-cel
  Cilta-cel will be administered as intravenous infusion.
• Drug Cyclophosphamide
  Cyclophosphamide will be administered as intravenous infusion.
• Drug Induction therapy
  Induction therapy consist of bortezomib, lenalidomide, and dexamethasone (VRd) or daratumumab, lenalidomide, and dexamethasone (DRd) or daratumumab, bortezomib, lenalidomide, and dexamethasone (DVRd), will will be administered.
• Drug Fludarabine
  Fludarabine will be administered as intravenous infusion.

Primary outcome measures

• Minimal Residual Disease (MRD)-negative Complete Response (CR) After Cilta-cel Infusion [Time frame: At least 12 months after Cilta-cel infusion on Day 1]

Secondary outcome measures (9)

• Overall MRD-negative CR Rate [Time frame: From study start until progressive disease, subsequent therapy or end of study, whichever is earlier (Up to 3 years and 4 months)]
• CR or better status [Time frame: From study start until progressive disease, subsequent therapy or end of study, whichever is earlier (Up to 3 years and 4 months)]
• Progression Free Survival (PFS) [Time frame: From study start until progressive disease, subsequent therapy or end of study, whichever is earlier (Up to 3 years and 4 months)]
• Overall Survival (OS) [Time frame: Up to 3 years and 4 months]
• Number of Participants with Adverse Event (AE) by Severity [Time frame: Up to 3 years and 4 months]
• Number of Participants with Abnormalities in Laboratory Parameters [Time frame: Up to 3 years and 4 months]
• Levels of Cilta-cel T-Cell Expansion, and Persistence [Time frame: Up to 3 years and 4 months]
• Number of Participants with Anti-Cilta-Cel Antibodies [Time frame: Up to 3 years and 4 months]
• Percentage of Participants with Presence of Replication-competent Lentivirus (RCL) [Time frame: Up to 3 years and 4 months]

Eligibility criteria

Inclusion criteria

• Documented diagnosis of newly diagnosed multiple myeloma (NDMM) according to the most recent international myeloma working group (IMWG) diagnostic criteria and measurable disease at diagnosis (prior to start of any anti-myeloma therapy): Serum monoclonal paraprotein (M-protein) level greater than equal to (>=)1.0 grams per deciliter (g/dL) or urine M-protein level >= 200 milligrams (mg)/24 hours; or light chain multiple myeloma in whom the only measurable disease is by serum free light chain (FLC) levels in the serum: involved serum free light chain >= 10 mg/dL and abnormal serum free light chain ratio
• Not considered a candidate for high-dose chemotherapy with stem cell transplantation due to: (a) Advanced age; or (b) Presence of comorbid condition(s) likely to have a negative impact on tolerability of high-dose chemotherapy with stem cell transplantation; or (c) Participant refusal of high-dose chemotherapy with stem cell transplantation as initial treatment
• Participant must have received at least 3 cycles and no more than 5 cycles of induction therapy. Initially, only participants receiving triplet induction therapy with DRd or VRd will be enrolled. Only after sponsor notification, participants receiving quadruplet DVRd induction therapy may be enrolled (screening can commence as early as during Cycle 3 of induction). Participants must have achieved >= partial response (PR) on the most recent disease assessment to be enrolled
• Eastern cooperative oncology group (ECOG) Performance Status score of 0 or 1
• Must be willing and able to adhere to the lifestyle restrictions specified in the protocol

Exclusion criteria

• Frailty index of >= 2 according to Myeloma Geriatric Assessment score
• Known allergies, hypersensitivity, or intolerance to study intervention or its active agents
• Grade 2 or higher ongoing non-hematologic toxicity due to induction therapy, with the exception of grade 2 peripheral neuropathy due to bortezomib
• Participants who require continuous supplemental oxygen

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

Spain · 8 centers

• Hosp. Univ. Germans Trias I Pujol — Badalona
• Hosp Univ Vall D Hebron — Barcelona
• Hosp. Clinic de Barcelona — Barcelona
• Hosp. Univ. 12 de Octubre — Madrid
• Clinica Univ. de Navarra — Pamplona
• Hosp Clinico Univ de Salamanca — Salamanca
• Hosp. Univ. Marques de Valdecilla — Santander
• Hosp. Virgen Del Rocio — Seville

United States · 5 centers

• University of California San Francisco — San Francisco
• Moffitt Cancer Center — Tampa
• University of Iowa Hospital and Clinics — Iowa City
• Memorial Sloan Kettering Cancer Center — New York
• Cleveland Clinic — Cleveland

Australia · 4 centers

• Royal Prince Alfred Hospital — Camperdown
• Austin Hospital — Heidelberg
• Fiona Stanley Hospital — Murdoch
• Princess Alexandra Hospital — Woolloongabba

Identifiers

NCT: NCT07149857 · 68284528MMY2012 · 68284528MMY2012 · 2025-521975-30-00

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗