Cilta‑cel with a fludarabine‑free or alternative lymphodepletion plan for multiple myeloma

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

This trial tests whether giving cilta‑cel with a fludarabine‑free lymphodepletion or with an alternative timing after cyclophosphamide and fludarabine works and is safe for people with newly diagnosed multiple myeloma who are not candidates for high‑dose transplant.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 60 (estimated)
• Ages: 18 Years to 80 Years
• Sex: All
• Sponsor: Janssen Research & Development, LLC (Industry-sponsored)
• Drugs / interventions: chemotherapy, cyclophosphamide, fludarabine
• Locations: 17 sites (San Francisco, California and 16 other locations)
• Trial ID: NCT07149857 on ClinicalTrials.gov

What this trial studies

This Phase 2 interventional trial gives cilta‑cel (a CAR‑T cell therapy) to patients with newly diagnosed, measurable multiple myeloma who are not candidates for high‑dose chemotherapy with stem cell transplant. Participants receive cilta‑cel either after a fludarabine‑free lymphodepletion regimen or following cyclophosphamide plus fludarabine with an alternative infusion timing. The study measures response rates and safety outcomes to compare efficacy and tolerability of the different lymphodepletion approaches. It is sponsored by Janssen and conducted at several US cancer centers.

Who should consider this trial

Good fit: Ideal candidates are adults with newly diagnosed, measurable multiple myeloma who are not considered candidates for high‑dose chemotherapy with stem cell transplant because of age, comorbidities, or personal refusal.

Not a fit: Patients who are eligible for high‑dose chemotherapy with stem cell transplant, those with relapsed or refractory disease, or those without measurable disease at diagnosis are unlikely to benefit or be eligible.

Why it matters

Potential benefit: If successful, this approach could provide an effective CAR‑T option for transplant‑ineligible patients with less toxic or more convenient lymphodepletion.

How similar studies have performed: Other cilta‑cel trials have shown high response rates in later‑line multiple myeloma, but using a fludarabine‑free lymphodepletion or altered infusion timing in newly diagnosed patients is less well tested.

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

Where this trial is running

San Francisco, California and 16 other locations

• University of California San Francisco — San Francisco, California, United States (Recruiting)
• Moffitt Cancer Center — Tampa, Florida, United States (Active_not_recruiting)
• University of Iowa Hospital and Clinics — Iowa City, Iowa, United States (Active_not_recruiting)
• Memorial Sloan Kettering Cancer Center — New York, New York, United States (Active_not_recruiting)
• Cleveland Clinic — Cleveland, Ohio, United States (Recruiting)
• Royal Prince Alfred Hospital — Camperdown, Australia (Recruiting)
• Austin Hospital — Heidelberg, Australia (Recruiting)
• Fiona Stanley Hospital — Murdoch, Australia (Recruiting)
• Princess Alexandra Hospital — Woolloongabba, Australia (Recruiting)
• Hosp. Univ. Germans Trias I Pujol — Badalona, Spain (Recruiting)
• Hosp Univ Vall D Hebron — Barcelona, Spain (Recruiting)
• Hosp. Clinic de Barcelona — Barcelona, Spain (Recruiting)
• Hosp. Univ. 12 de Octubre — Madrid, Spain (Recruiting)
• Clinica Univ. de Navarra — Pamplona, Spain (Recruiting)
• Hosp Clinico Univ de Salamanca — Salamanca, Spain (Recruiting)
• Hosp. Univ. Marques de Valdecilla — Santander, Spain (Recruiting)
• Hosp. Virgen Del Rocio — Seville, Spain (Recruiting)

Study contacts

• Study coordinator: Study Contact

Conditions Multiple Myeloma