TBI + Cyclophosphamide + Ciltacabtagene Autoleucel for Multiple Myeloma

Overseen By Michael J Slade, M.D., MSCI

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Washington University School of Medicine

Must not be taking: Investigational agents

Disqualifiers: Pregnancy, Uncontrolled illness, HIV, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

12 Participants Needed

Trial Summary

Do I need to stop my current medications to join the trial?

The trial information does not specify if you need to stop taking your current medications. However, you cannot be on any other investigational agents while participating.

What data supports the effectiveness of the treatment Ciltacabtagene Autoleucel for Multiple Myeloma?

Ciltacabtagene autoleucel (cilta-cel) has shown effectiveness in patients with relapsed or refractory multiple myeloma, particularly those who have already tried other treatments. It has been approved by the FDA as a fifth-line option for these patients, indicating its potential benefit when other treatments have failed. ^{1 2 3 4 5}

Is ciltacabtagene autoleucel (cilta-cel) safe for humans?

Ciltacabtagene autoleucel (cilta-cel) has been approved by the FDA for treating multiple myeloma and has a tolerable safety profile, with adverse effects that range from mild to life-threatening but are mostly manageable. It has shown a consistent safety profile over longer follow-up periods. ^{1 2 6 7 8}

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 a novel approach for patients with relapsed or refractory multiple myeloma who have tried multiple other treatments. It involves modifying a patient's own T-cells to better recognize and attack cancer cells, providing deep and long-lasting responses compared to conventional treatments. ^{1 2 3 6 7}

What is the purpose of this trial?

Treatment for relapsed/refractory multiple myeloma continues to evolve with the approval of highly effective anti-BCMA CAR T therapies in recent years. However, despite the high prevalence of renal insufficiency in this population, pivotal clinical trials have excluded patients with impaired renal function, leading to an urgent, unmet clinical need to develop safe and effective lymphodepleting regimens prior to CAR T administration for this population. In addition, renal insufficiency is linked to poor disease-related outcomes and is highly associated with several underserved populations. This study is testing the hypotheses that: 1. low-dose total body irradiation (TBI) in combination with cyclophosphamide (Cy) as lymphodepletion prior to administration of cilta-cel will be safe and tolerable in patients with multiple myeloma who have impaired renal function 2. low-dose TBI-Cy as lymphodepletion prior to cilta-cel will result in comparable CAR T expansion/persistence and disease response rates as those seen with standard lymphodepleting chemotherapy (fludarabine / cyclophosphamide).

Research Team

Michael Slade, M.D.

Principal Investigator

Washington University School of Medicine

Eligibility Criteria

This trial is for multiple myeloma patients who have kidney problems and haven't responded well to other treatments. They're testing a new way to prepare these patients for CAR T-cell therapy, which is a type of cancer treatment.

Inclusion Criteria

My diagnosis of multiple myeloma is confirmed through tissue analysis.

Women of childbearing potential and men must agree to use adequate contraception prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study or should a man suspect he has fathered a child, s/he must inform her treating physician immediately

My kidney function is low, with an eGFR below 45.

Exclusion Criteria

Currently receiving any other investigational agents

Pregnant and/or breastfeeding. Women of childbearing potential must have a negative pregnancy test within 14 days of study entry

I have another cancer that won't affect this cancer treatment's safety or results.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Lymphodepletion

Participants receive low-dose total body irradiation (TBI) in combination with cyclophosphamide (Cy) as lymphodepletion prior to administration of cilta-cel

5 days

Daily visits for treatment administration

Cilta-cel Infusion

Participants receive cilta-cel infusion following lymphodepletion

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including tracking of adverse events and overall survival

1 year and 1 week

Regular visits as per protocol

Treatment Details

Interventions

• Ciltacabtagene Autoleucel
• Cyclophosphamide
• Total body irradiation

Trial Overview Researchers are looking at how safe it is to use low-dose total body irradiation with cyclophosphamide as preparation before giving patients cilta-cel, a CAR T-cell therapy. They want to see if this method works as well as the standard prep treatment.

Participant Groups

Group I: Cyclophosphamide + Cilta-Cel + TBI Experimental Treatment 3 Interventions

All patients will undergo T-cell collection and CAR T manufacturing as per standard of care. Patients will receive cyclophosphamide per standard of care Day -5 to Day -3. They will subsequently receive TBI on Day -1 then and will receive cilta-cel infusion on Day 0.

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

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

Who Is Running the Clinical Trial?

Washington University School of Medicine

Lead Sponsor

Trials

2,027

Recruited

2,353,000+

American Cancer Society, Inc.

Collaborator

Trials

237

Recruited

110,000+

Cures Within Reach

Collaborator

Trials

25

Recruited

2,100+

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.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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]

Ciltacabtagene autoleucel (cilta-cel) showed significantly better overall response rates and complete response rates compared to idecabtagene vicleucel (ide-cel) in patients with relapsed or refractory multiple myeloma, based on a comparative analysis of individual patient data from 1 trial and published data from another.

Cilta-cel also demonstrated improved duration of response and progression-free survival, indicating its potential as a more effective treatment option for patients previously treated with multiple therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Matching-adjusted indirect comparison of efficacy outcomes for ciltacabtagene autoleucel in CARTITUDE-1 versus idecabtagene vicleucel in KarMMa for the treatment of patients with relapsed or refractory multiple myeloma. Martin, T., Usmani, SZ., Schecter, JM., et al.[2022]

Ciltacabtagene autoleucel (cilta-cel) demonstrated significantly improved efficacy compared to three non-CAR-T therapies for treating relapsed or refractory multiple myeloma, with at least a 3.1-fold increase in overall response rates and a 10.3-fold increase in complete response rates.

Patients receiving cilta-cel experienced at least a 74% reduction in the risk of disease progression or death and a 47% reduction in the risk of death, indicating its strong potential as a treatment option for patients who have been previously treated with multiple therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Matching-Adjusted Indirect Treatment Comparison to Assess the Comparative Efficacy of Ciltacabtagene Autoleucel in CARTITUDE-1 Versus Belantamab Mafodotin in DREAMM-2, Selinexor-Dexamethasone in STORM Part 2, and Melphalan Flufenamide-Dexamethasone in HORIZON for the Treatment of Patients With Triple-Class Exposed Relapsed or Refractory Multiple Myeloma. Weisel, K., Krishnan, A., Schecter, JM., et al.[2022]

Ciltacabtagene autoleucel (cilta-cel) is a CAR T-cell therapy that effectively targets B-cell maturation antigen (BCMA) in patients with relapsed or refractory multiple myeloma, showing early and long-lasting responses based on the Phase 1b/2 CARTITUDE-1 study.

While cilta-cel has a tolerable safety profile with manageable adverse effects, it generally demonstrates better efficacy compared to another CAR T-cell therapy, idecabtagene vicleucel (ide-cel), although both therapies have comparable adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ciltacabtagene autoleucel: The second anti-BCMA CAR T-cell therapeutic armamentarium of relapsed or refractory multiple myeloma. Chekol Abebe, E., Yibeltal Shiferaw, M., Tadele Admasu, F., et al.[2022]

Ciltacabtagene autoleucel (cilta-cel) demonstrated significantly better efficacy compared to physician's choice of treatment in patients with relapsed or refractory multiple myeloma, with a relative risk of 2.95 for overall response rate and 111.70 for complete response or better.

The study showed that cilta-cel also improved progression-free survival and overall survival, with hazard ratios of 0.24 and 0.21 respectively, indicating it could be a promising new treatment option for patients who have already been exposed to multiple therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative Efficacy of Ciltacabtagene Autoleucel in CARTITUDE-1 vs Physician's Choice of Therapy in the Long-Term Follow-Up of POLLUX, CASTOR, and EQUULEUS Clinical Trials for the Treatment of Patients with Relapsed or Refractory Multiple Myeloma. Weisel, K., Martin, T., Krishnan, A., et al.[2022]

Ciltacabtagene autoleucel (cilta-cel) is a CAR-T therapy for adult patients with relapsed or refractory multiple myeloma, and the estimated average healthcare costs for administering this therapy in the US are approximately $160,933 per patient over a 12-month period, excluding the cost of the therapy itself.

The analysis highlights various cost components associated with cilta-cel therapy, including apheresis, bridging therapy, and management of adverse events, which can aid healthcare decision-makers in evaluating the economic implications of this treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Component Costs of CAR-T Therapy in Addition to Treatment Acquisition Costs in Patients with Multiple Myeloma. Jagannath, S., Joseph, N., Crivera, C., et al.[2023]

References

1. United States pubmed.ncbi.nlm.nih.gov

Cilta-cel or Standard Care in Lenalidomide-Refractory Multiple Myeloma. [2023]

2. United States pubmed.ncbi.nlm.nih.gov

Cilta-cel OK'd for Multiple Myeloma. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

Comparison of Cilta-cel, an Anti-BCMA CAR-T Cell Therapy, Versus Conventional Treatment in Patients With Relapsed/Refractory Multiple Myeloma. [2022]

4. England pubmed.ncbi.nlm.nih.gov

Matching-adjusted indirect comparison of efficacy outcomes for ciltacabtagene autoleucel in CARTITUDE-1 versus idecabtagene vicleucel in KarMMa for the treatment of patients with relapsed or refractory multiple myeloma. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

Matching-Adjusted Indirect Treatment Comparison to Assess the Comparative Efficacy of Ciltacabtagene Autoleucel in CARTITUDE-1 Versus Belantamab Mafodotin in DREAMM-2, Selinexor-Dexamethasone in STORM Part 2, and Melphalan Flufenamide-Dexamethasone in HORIZON for the Treatment of Patients With Triple-Class Exposed Relapsed or Refractory Multiple Myeloma. [2022]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Ciltacabtagene autoleucel: The second anti-BCMA CAR T-cell therapeutic armamentarium of relapsed or refractory multiple myeloma. [2022]

7. New Zealand pubmed.ncbi.nlm.nih.gov

Comparative Efficacy of Ciltacabtagene Autoleucel in CARTITUDE-1 vs Physician's Choice of Therapy in the Long-Term Follow-Up of POLLUX, CASTOR, and EQUULEUS Clinical Trials for the Treatment of Patients with Relapsed or Refractory Multiple Myeloma. [2022]

8. New Zealand pubmed.ncbi.nlm.nih.gov

Component Costs of CAR-T Therapy in Addition to Treatment Acquisition Costs in Patients with Multiple Myeloma. [2023]