Anitocabtagene Autoleucel for Multiple Myeloma

(iMMagine-3 Trial)

Recruiting at 120 trial locations

Overseen By Medical Information

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Kite, A Gilead Company

Must be taking: Immunomodulatory drugs, Anti-CD38 antibodies

Must not be taking: Systemic steroids, Immunosuppressive therapy

Disqualifiers: CNS involvement, Plasma cell leukemia, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 3-4 weeks

450 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called anitocabtagene autoleucel, a type of CAR-T cell therapy, for people with multiple myeloma—a type of blood cancer—that has returned or hasn't responded to previous treatments. The goal is to determine if this new treatment works better than the usual treatments. Participants will be divided into two groups: one will receive the experimental treatment, and the other will receive one of the standard therapy options. Suitable candidates have had multiple myeloma and tried 1 to 3 different treatments before, including specific drugs like anti-CD38 monoclonal antibodies. As a Phase 3 trial, this treatment is in the final step before FDA approval, offering participants a chance to access potentially groundbreaking therapy.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, if you are on high-dose steroids or other immunosuppressive therapy, you may need to stop them at least 14 days before joining the trial.

Is there any evidence suggesting that anitocabtagene autoleucel is likely to be safe for humans?

Research shows that anitocabtagene autoleucel, or "anito-cel," has undergone thorough safety testing in people with relapsed or refractory multiple myeloma. In earlier studies, 95% of participants received anito-cel and experienced close monitoring. Most participants found the treatment manageable, though some side effects occurred, as with any treatment.

One study found that anito-cel was effective for many patients, suggesting its promise. It's important to remember that all new treatments can carry risks, and side effects may require careful attention. The results so far are encouraging regarding safety. Always consult a doctor to understand what this could mean for individual circumstances. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about anitocabtagene autoleucel for multiple myeloma because it uses a cutting-edge approach called CAR-T cell therapy. Unlike standard treatments like pomalidomide, bortezomib, and dexamethasone, which work by targeting cancer cells with drugs, anitocabtagene autoleucel involves modifying a patient's own immune cells to better recognize and attack the cancer. This personalized approach not only offers the potential for a more targeted attack on multiple myeloma cells but also promises longer-lasting effects since the modified cells continue to patrol the body for cancer. This innovative therapy represents a significant shift from traditional drug-based regimens, potentially providing new hope for patients with relapsed or refractory multiple myeloma.

What evidence suggests that anitocabtagene autoleucel could be an effective treatment for multiple myeloma?

Research has shown that anitocabtagene autoleucel, which participants in this trial may receive, may effectively treat relapsed or hard-to-treat multiple myeloma. One study found that 97% of patients responded well to this treatment, with effects lasting a long time, indicating durability. This treatment targets BCMA, a protein on multiple myeloma cells, aiding the immune system in attacking and destroying them. These findings suggest that anitocabtagene autoleucel could be a good option for individuals who have already tried other treatments. ^{1 2 3 4 6}

Who Is on the Research Team?

Kite Study Director

Principal Investigator

Kite, A Gilead Company

Are You a Good Fit for This Trial?

This trial is for people with relapsed/refractory multiple myeloma who've had 1-3 prior treatments including an anti-CD38 antibody and an immunomodulatory drug. They should have measurable disease indicators, be able to receive one of the standard therapies, and have good physical function (ECOG status 0 or 1). Women must not be pregnant and if of childbearing potential, need a negative pregnancy test.

Inclusion Criteria

I have been diagnosed with multiple myeloma.

I've had 1-3 prior treatments for myeloma, including specific types of therapy.

My blood or urine tests show high protein levels indicating myeloma.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive lymphodepletion chemotherapy followed by a single dose of anitocabtagene autoleucel or standard of care therapy

3-4 weeks

Post-treatment Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 4 years

Long-term Follow-up

Participants transition to a separate long-term follow-up study to continue follow-up out to 15 years

Up to 15 years

What Are the Treatments Tested in This Trial?

Interventions

• Anitocabtagene Autoleucel

Trial Overview The study compares anitocabtagene autoleucel (a new therapy) against standard of care options like Bortezomib or Carfilzomib combinations in participants with multiple myeloma. It measures how long patients live without their disease getting worse by using independent reviews.

How Is the Trial Designed?

Group I: Anitocabtagene Autoleucel Experimental Treatment 3 Interventions

Participants with RRMM will receive lymphodepletion chemotherapy with cyclophosphamide and fludarabine for 3 days followed by single dose of anitocabtagene autoleucel chimeric antigen receptor positive (CAR+) on Day 1.

Group II: Standard of Care Therapy (SOCT) Active Control 5 Interventions

Participants will receive the investigator's choice of one of the following therapies: * pomalidomide, bortezomib, and dexamethasone (PVd) (21-day cycles) * daratumumab, pomalidomide, and dexamethasone (DPd) (28-day cycles) * carfilzomib, daratumumab, and dexamethasone (KDd) (28-day cycles) * carfilzomib and dexamethasone (Kd) (28-day cycles)

Who Is Running the Clinical Trial?

Kite, A Gilead Company

Lead Sponsor

Trials

45

Recruited

4,300+

Arcellx, Inc.

Industry Sponsor

Trials

5

Recruited

650+

Published Research Related to This Trial

In a phase 3 trial with 386 patients suffering from relapsed and refractory multiple myeloma, idecabtagene vicleucel (ide-cel) significantly improved progression-free survival (13.3 months) compared to standard treatments (4.4 months), indicating its efficacy in this challenging patient population.

The treatment with ide-cel resulted in a 71% overall response rate, including a 39% complete response rate, although it was associated with high rates of adverse events (93% grade 3 or 4), including cytokine release syndrome in 88% of patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ide-cel or Standard Regimens in Relapsed and Refractory Multiple Myeloma. Rodriguez-Otero, P., Ailawadhi, S., Arnulf, B., 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]

In a retrospective analysis of 7 patients with prior allogeneic stem cell transplants (alloSCT) who received cilta-cel, an overall response rate of 85.7% was observed, indicating that cilta-cel is effective even in this heavily pretreated group.

The safety profile of cilta-cel in patients with prior alloSCT was similar to that of patients without alloSCT, with manageable side effects like cytokine release syndrome and no reported cases of graft-versus-host disease, suggesting that cilta-cel may be a viable treatment option for these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ciltacabtagene Autoleucel in Patients With Prior Allogeneic Stem Cell Transplant in the CARTITUDE-1 Study. Htut, M., Dhakal, B., Cohen, AD., et al.[2023]

Axicabtagene ciloleucel and brexucabtagene autoleucel are effective anti-CD19 T-cell therapies that have shown high response rates in patients with relapsed and refractory B-cell malignancies, leading to FDA approvals for specific types of lymphoma.

Despite their effectiveness, these therapies can cause significant toxicities, such as cytokine release syndrome and neurologic issues, which necessitate careful management and monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Axicabtagene ciloleucel and brexucabtagene autoleucel in relapsed and refractory diffuse large B-cell and mantle cell lymphomas. Reagan, PM., Friedberg, JW.[2021]

CAR-T therapies, specifically idecabtagene vicleucel (ide-cel) and ciltacabtagene autoleucel (cilta-cel), show significant potential in treating heavily pretreated relapsed/refractory multiple myeloma (RRMM), with updated clinical trial data indicating they can elicit responses in these patients.

Indirect comparisons suggest that cilta-cel may provide deeper and more durable responses than ide-cel in patients with triple class-exposed RRMM, although direct head-to-head trials are necessary to confirm these findings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recent Advances in the Use of Chimeric Antigen Receptor-Expressing T-Cell Therapies for Treatment of Multiple Myeloma. Martin, T., Jackson, CC., Pacaud, L., 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]

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) 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) 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) showed significantly improved progression-free survival (PFS), time to next treatment (TTNT), and overall survival (OS) compared to physician's choice of treatment in patients with relapsed or refractory multiple myeloma, with hazard ratios indicating strong benefits (HR: 0.18 for PFS, HR: 0.15 for TTNT, HR: 0.25 for OS).

The study utilized real-world data from the Flatiron Health multiple myeloma cohort to compare cilta-cel's effectiveness, ensuring balanced baseline characteristics through inverse probability of treatment weighting, which supports the robustness of the findings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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. Martin, T., Krishnan, A., Yong, K., et al.[2023]

Citations

1. ashpublications.org ashpublications.org/blood/article/144/Supplement%201/4825/533294/Phase-1-Study-of-Anitocabtagene-Autoleucel-for-the

Phase 1 Study of Anitocabtagene Autoleucel for the Treatment ... Additional pt population details and longer-term efficacy and safety outcomes for this Phase 1 first-in-human clinical trial are reported.

2. arcellx.com arcellx.com/wp-content/uploads/2024/06/Anito-cel-EHA-2024.pdf

Anitocabtagene autoleucel (anito-cel/CART-ddBCMA) Phase 1 Study Of CART-ddBCMA For The Treatment Of Patients. With Relapsed And/Or Refractory Multiple Myeloma: Results. From At Least 1-year Follow-up In All ...

3. onclive.com onclive.com/view/anito-cel-drives-durable-responses-in-r-r-multiple-myeloma

Anito-Cel Drives Durable Responses in R/R Multiple ... Anitocabtagene autoleucel yielded an overall response rate of 97% in relapsed/refractory multiple myeloma.

4. ash.confex.com ash.confex.com/ash/2024/webprogram/Paper198499.html

Phase 2 Registrational Study of Anitocabtagene Autoleucel ... Efficacy outcomes were assessed using 2016 International Myeloma Working Group (IMWG) criteria, minimal residual disease (MRD) was assessed by ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT05396885

NCT05396885 | Study of Anitocabtagene-autoleucel in ... Following a single infusion of anitocabtagene-autoleucel both safety and efficacy data will be assessed. Efficacy will be assessed monthly for the first 6 ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT04155749

NCT04155749 | Study of Anitocabtagene-autoleucel in ... Master protocol for cell therapy, Phase 1 proof-of-concept studies in relapsed and refractory multiple myeloma and includes long-term safety follow-up. Official ...