20 Participants Needed

CAR T-Cell Therapy for Multiple Myeloma

IG
HS
HW
Overseen ByHope Wei
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)
Prior Safety DataThis treatment has passed at least one previous human trial
Approved in 2 JurisdictionsThis treatment is already approved in other countries

Trial Summary

What is the purpose of this trial?

The goal of this research study is to test if ciltacabtagene autoleucel (cilta-cel) is safe and effective in treating participants with high-risk, smoldering myeloma. The names of the treatment interventions used in this study are: * Cilta-cel (or chimeric antigen receptor T cells) * Cyclophosphamide (a lymphodepleting chemotherapy) * Fludarabine (a lymphodepleting chemotherapy)

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, certain therapies like chemotherapy, immunotherapy, and radiotherapy are not allowed during the trial, so it's best to discuss your specific medications with the study team.

What data supports the effectiveness of the treatment Ciltacabtagene Autoleucel (cilta-cel) for multiple myeloma?

Ciltacabtagene autoleucel (cilta-cel) has shown to be effective in patients with relapsed or refractory multiple myeloma, especially those who have already tried several other treatments. It has been approved by the FDA as a fifth-line option due to its ability to induce early, deep, and long-lasting responses, as demonstrated in the CARTITUDE-1 study.12345

Is CAR T-Cell Therapy for Multiple Myeloma safe?

Ciltacabtagene autoleucel (cilta-cel) is generally considered safe for treating multiple myeloma, with most side effects being manageable. Patients may experience mild to life-threatening adverse effects, but these are mostly manageable, and the safety profile remains consistent over time.12467

What makes the treatment ciltacabtagene autoleucel unique for multiple myeloma?

Ciltacabtagene autoleucel is a personalized CAR T-cell therapy that targets a specific protein (BCMA) on cancer cells, offering deep and long-lasting responses for patients with multiple myeloma who have tried many other treatments. It uses the patient's own modified T-cells to attack the cancer, making it a novel option compared to traditional therapies.12489

Research Team

Irene Ghobrial, MD - Dana-Farber Cancer ...

Irene Ghobrial, MD

Principal Investigator

Dana-Farber Cancer Institute

Eligibility Criteria

This trial is for adults over 18 with high-risk smoldering myeloma, which isn't yet causing symptoms. Participants should have certain blood and bone marrow conditions but no recent other cancers or major illnesses. They must be able to perform daily activities with ease (ECOG PS 0 or 1) and agree to use effective contraception.

Inclusion Criteria

I am a man and will use protection if I have sex with a woman who can have children.
You have a high percentage of certain bone marrow cells and specific changes in their patterns.
My condition is high-risk smoldering multiple myeloma with ≤40% plasma cells.
See 5 more

Exclusion Criteria

I have not had major surgery in the last 2 weeks.
I am not allergic or intolerant to the study drug or its components.
I do not have any unmanaged ongoing illnesses.
See 13 more

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Safety Run-In

Participants undergo apheresis, stem cell collection, and receive cyclophosphamide and fludarabine followed by hospitalization for Cilta-cel administration

3 weeks
Hospitalization for 2 weeks post Cilta-cel infusion

Cilta-Cel Dose Expansion

Expansion cohort participants undergo similar procedures as the safety run-in phase

3 weeks
Hospitalization for 2 weeks post Cilta-cel infusion

Follow-up

Participants are monitored for safety and effectiveness after treatment

3 years

Long-term Follow-up

Extended monitoring for safety and effectiveness up to 15 years

Up to 15 years

Treatment Details

Interventions

  • Ciltacabtagene Autoleucel
  • Cyclophosphamide
  • Fludarabine Phosphate
Trial OverviewThe study tests the safety and effectiveness of cilta-cel, a CAR T-cell therapy, along with cyclophosphamide and fludarabine phosphate chemotherapies in treating high-risk smoldering myeloma before it becomes symptomatic.
Participant Groups
2Treatment groups
Experimental Treatment
Group I: Safety Run-InExperimental Treatment3 Interventions
Participants will be enrolled into each of the 2 safety run-in phases in a standard 3 + 3 design. - Participants will undergo study procedures as outlined: * Apheresis for collection of peripheral blood mononuclear cells (PBMC) will occur on-site * Stem cell collection on-site post-apheresis per standard care. * Administration of Cyclophosphamide and fludarabine in pre-determined doses 1 x daily for 3 consecutive days. * Hospitalization to receive Cilta-cel in per-determined dose per protocol 1 x daily for 3 consecutive days and will remain in the hospital for 2 weeks post cilta-cell infusion. * Follow-up for 3 years post-treatment and up to 15 years.
Group II: Cilta-Cel Dose Expansion CohortExperimental Treatment3 Interventions
Expansion cohort of 14 participants will be enrolled after safety run-in phases, and participants will undergo study procedures as outlined: * Apheresis for collection of peripheral blood mononuclear cells (PBMC) will occur on-site * Stem cell collection on-site post-apheresis per standard care. * Administration of Cyclophosphamide and fludarabine in pre-determined doses 1 x daily for 3 consecutive days. * Hospitalization to receive Cilta-cel in per-determined dose per protocol 1 x daily for 3 consecutive days and will remain in the hospital for 2 weeks post cilta-cell infusion. * Follow-up for 3 years post-treatment and up to 15 years.

Ciltacabtagene Autoleucel is already approved in United States, European Union for the following indications:

🇺🇸
Approved in United States as Carvykti for:
  • Relapsed or refractory multiple myeloma after four or more prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody
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Approved in European Union as Carvykti for:
  • Relapsed and refractory multiple myeloma after one or more prior lines of therapy, including a proteasome inhibitor and an immunomodulatory agent, and are refractory to lenalidomide

Find a Clinic Near You

Who Is Running the Clinical Trial?

Dana-Farber Cancer Institute

Lead Sponsor

Trials
1,128
Recruited
382,000+

Janssen Research & Development, LLC

Industry Sponsor

Trials
1,022
Recruited
6,408,000+
Giacomo Salvadore profile image

Giacomo Salvadore

Janssen Research & Development, LLC

Chief Medical Officer since 2023

MD from the University of Rome, Tor Vergata

Ricardo Attar profile image

Ricardo Attar

Janssen Research & Development, LLC

Chief Executive Officer since 2008

PhD in Molecular Biology from the University of Buenos Aires

Findings from Research

Ciltacabtagene autoleucel (cilta-cel) significantly improved progression-free survival in patients with lenalidomide-refractory multiple myeloma, with a median progression-free survival not reached in the cilta-cel group compared to 11.8 months in the standard-care group, based on a phase 3 trial with 419 participants.
The cilta-cel group also showed higher overall response rates (84.6% vs. 67.3%) and complete response rates (73.1% vs. 21.8%) compared to standard care, although most patients experienced grade 3 or 4 adverse events, including cytokine release syndrome.
Cilta-cel or Standard Care in Lenalidomide-Refractory Multiple Myeloma.San-Miguel, J., Dhakal, B., Yong, K., et al.[2023]
Ciltacabtagene autoleucel (cilta-cel) has been approved by the FDA as a fifth-line treatment option for patients with relapsed or refractory multiple myeloma, marking a significant advancement in therapy options for this challenging condition.
Cilta-cel is notable for being the second chimeric antigen receptor T-cell therapy targeting BCMA to receive regulatory approval within a year, highlighting the rapid development of innovative treatments in this area.
Cilta-cel OK'd for Multiple Myeloma.[2022]
Ciltacabtagene autoleucel (cilta-cel) demonstrated a significantly higher overall response rate (84% vs. 28%) and longer progression-free survival in patients with relapsed/refractory multiple myeloma compared to standard non-CAR-T therapies, based on a comparison of 113 patients in the CARTITUDE-1 study and 190 patients from the MAMMOTH dataset.
In the modified intent-to-treat population, cilta-cel showed an even more impressive overall response rate of 96% compared to 30% in the MAMMOTH cohort, indicating its potential as a highly effective treatment option for patients who have exhausted other therapies.
Comparison of Cilta-cel, an Anti-BCMA CAR-T Cell Therapy, Versus Conventional Treatment in Patients With Relapsed/Refractory Multiple Myeloma.Costa, LJ., Lin, Y., Cornell, RF., et al.[2022]

References

Cilta-cel or Standard Care in Lenalidomide-Refractory Multiple Myeloma. [2023]
Cilta-cel OK'd for Multiple Myeloma. [2022]
Comparison of Cilta-cel, an Anti-BCMA CAR-T Cell Therapy, Versus Conventional Treatment in Patients With Relapsed/Refractory Multiple Myeloma. [2022]
Ciltacabtagene autoleucel: The second anti-BCMA CAR T-cell therapeutic armamentarium of relapsed or refractory multiple myeloma. [2022]
Patient Perceptions Regarding Ciltacabtagene Autoleucel Treatment: Qualitative Evidence From Interviews With Patients With Relapsed/Refractory Multiple Myeloma in the CARTITUDE-1 Study. [2023]
Component Costs of CAR-T Therapy in Addition to Treatment Acquisition Costs in Patients with Multiple Myeloma. [2023]
Comparative effectiveness of ciltacabtagene autoleucel in CARTITUDE-1 versus physician's choice of therapy in the Flatiron Health multiple myeloma cohort registry for the treatment of patients with relapsed or refractory multiple myeloma. [2023]
Five-year remission without disease progression in a patient with relapsed/refractory multiple myeloma with extramedullary disease treated with LCAR-B38M chimeric antigen receptor T cells in the LEGEND-2 study: a case report. [2022]
Ciltacabtagene autoleucel for the treatment of multiple myeloma. [2023]