TBI + Cyclophosphamide + Ciltacabtagene Autoleucel for Multiple Myeloma

Recruiting at 1 trial location

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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to find a safe and effective way to treat multiple myeloma, a type of cancer, in individuals with kidney issues. Researchers are testing whether a combination of low-dose total body irradiation (TBI) and the drug cyclophosphamide can prepare patients for CAR T-cell therapy, specifically using ciltacabtagene autoleucel, which employs modified immune cells to target cancer. The study aims to demonstrate that this new approach is as effective as the current standard treatment. Individuals with multiple myeloma and reduced kidney function, who have struggled with treatment options, might be suitable candidates for this trial. As a Phase 1 trial, the research focuses on understanding how the treatment works in participants, offering them the opportunity to be among the first to receive this innovative therapy.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

A previous study found ciltacabtagene autoleucel (cilta-cel) to be safe for patients with relapsed or refractory multiple myeloma. Approved in 2022 for this condition, it is generally well-tolerated. Some patients have experienced side effects, but these are often manageable.

Cyclophosphamide, commonly used in cancer treatment, is known for its safety. It can cause side effects like nausea or hair loss, but these usually don't last long.

Total body irradiation (TBI) is also used in cancer treatments. While it can have side effects, low doses are usually well-tolerated.

Overall, the combination of these treatments is expected to be safe. This trial will provide more specific information for patients with kidney problems. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard treatments for multiple myeloma, which often include drugs like lenalidomide or bortezomib, ciltacabtagene autoleucel (cilta-cel) is a cutting-edge CAR T-cell therapy. This treatment is unique because it involves reprogramming a patient’s own T-cells to specifically target and destroy cancer cells. Researchers are excited about cilta-cel because it offers a personalized approach that can potentially lead to longer-lasting remissions by directly targeting and eliminating the cancerous cells in the body. This could be a game-changer for patients who have exhausted other treatment options.

What evidence suggests that this trial's treatments could be effective for multiple myeloma?

Research has shown that Ciltacabtagene Autoleucel, or cilta-cel, holds promise for treating relapsed or refractory multiple myeloma. Participants in this trial will receive a combination of Cyclophosphamide, Total Body Irradiation (TBI), and cilta-cel. One study found that many patients had no detectable cancer cells after treatment with cilta-cel, indicating its effectiveness in reducing cancer signs. Another study found that patients lived longer without disease progression. These findings support cilta-cel as a strong option for individuals with multiple myeloma. ^{6 7 8 9 10}

Who Is on the Research Team?

Michael Slade, M.D.

Principal Investigator

Washington University School of Medicine

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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) 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 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]

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) 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) 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) 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) 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]

Citations

1.

ashpublications.org

ashpublications.org/blood/article/144/Supplement%201/2411.2/532383/Real-World-Efficacy-Outcomes-of-Ciltacabtagene

Real-World Efficacy Outcomes of Ciltacabtagene Autoleucel in ...

Real-world efficacy outcomes of Ciltacabtagene Autoleucel in relapsed refractory multiple myeloma: a comparative study with the Cartitude-1 trial.

2.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/40768190/

Comparative Effectiveness of Ciltacabtagene Autoleucel in ...

Outcomes for comparative effectiveness included progression-free survival (PFS), RW PFS, time to next treatment (TTNT), and overall survival (OS) ...

3.

jnj.com

jnj.com/innovativemedicine/emea/carvykti-ciltacabtagene-autoleucel-cilta-cel-demonstrated-significantly-higher-rates-of-minimal-residual-disease-negativity-compared-to-standard-therapies-in-the-cartitude-4-study

CARVYKTI®▼ (ciltacabtagene autoleucel; cilta-cel ...

89 percent of patients evaluable for minimal residual disease (MRD) assessment were MRD negative, with the majority reaching MRD negativity in less than 2 ...

4.

ascopubs.org

ascopubs.org/doi/10.1200/JCO-25-00760

Long-Term (≥5-Year) Remission and Survival After ...

CARTITUDE-1 evaluated ciltacabtagene autoleucel (cilta-cel) in patients with heavily pretreated relapsed/refractory multiple myeloma (RRMM).

5.

sciencedirect.com

sciencedirect.com/science/article/abs/pii/S2152265025042260

Real-World Efficacy Outcomes of Ciltacabtagene ...

Real-World Efficacy Outcomes of Ciltacabtagene Autoleucel in Relapsed Refractory Multiple Myeloma: A Comparative Study with the Cartitude-1 ...

6.

ashpublications.org

ashpublications.org/blood/article/145/1/85/518044/Safety-and-efficacy-of-standard-of-care

Safety and efficacy of standard-of-care ciltacabtagene ...

Ciltacabtagene autoleucel (cilta-cel) was approved in 2022 for patients with relapsed/refractory multiple myeloma (RRMM). We report outcomes ...

7.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/39365257/

Safety and efficacy of standard-of-care ciltacabtagene ...

Ciltacabtagene autoleucel (cilta-cel) was approved in 2022 for patients with relapsed/refractory multiple myeloma (RRMM). We report outcomes ...

8.

jnj.com

jnj.com/media-center/press-releases/single-infusion-of-carvykti-ciltacabtagene-autoleucel-delivered-lasting-treatment-free-remissions-for-at-least-five-years-in-patients-with-relapsed-or-refractory-multiple-myeloma

Single infusion of CARVYKTI® (ciltacabtagene autoleucel) ...

New long-term CARTITUDE-1 data show one-third of patients treated with CARVYKTI® remain progression-free

9.

multiplemyelomahub.com

multiplemyelomahub.com/medical-information/real-world-data-on-the-safety-and-efficacy-of-cilta-cel-in-patients-with-rrmm

Real-world data on the safety and efficacy of cilta-cel in ...

We summarize results from a retrospective analysis assessing the safety and efficacy of ciltacabtagene autoleucel in a real-world population ...

10.

carvyktihcp.com

carvyktihcp.com/cartitude-4-efficacy/

CARTITUDE-4 Study - CARVYKTI® (ciltacabtagene autoleucel)

CARTITUDE-4 is a randomized, open label, multicenter controlled study in adult patients with relapsed and lenalidomide-refractory multiple myeloma.