Combination Therapies for Multiple Myeloma

(aMMbition Trial)

Not currently recruiting at 19 trial locations

Overseen By Study Contact

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Janssen Research & Development, LLC

Disqualifiers: Myelodysplastic syndrome, B-cell malignancy, others

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

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

Compensation: Varies

Number of Visits: 12

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the effectiveness of combination therapies for treating multiple myeloma, a type of blood cancer. Researchers are testing two treatment combinations, including Cilta-cel (a type of CAR-T cell therapy), to determine which more effectively eliminates cancer cells, aiming for no signs of cancer for at least five years. The trial focuses on individuals newly diagnosed with standard-risk multiple myeloma who have not started other treatments. As a Phase 2 trial, it measures the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to important advancements in cancer therapy.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

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

A previous study found cilta-cel, a treatment for relapsed or hard-to-treat multiple myeloma, to be safe. Approved for use in 2022, about 89% of patients experienced cancer improvement, with 70% showing no signs of cancer. This indicates that cilta-cel is generally well-tolerated.

Research has also shown that talquetamab, another treatment for multiple myeloma, is generally safe. Patients faced a low risk of serious infections, making it a promising option to combine with other treatments. The FDA has approved talquetamab for patients who have tried several other treatments.

Both cilta-cel and talquetamab have demonstrated good safety results in past studies, suggesting they are generally safe for use in clinical trials. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for multiple myeloma because they leverage innovative approaches that differ from standard care options like lenalidomide, bortezomib, and dexamethasone. Cilta-cel is a CAR-T cell therapy uniquely engineered from a patient's own T-cells, which are designed to seek out and destroy myeloma cells, offering a personalized treatment strategy. Talquetamab, on the other hand, targets GPRC5D, a protein highly expressed on myeloma cells, providing a novel mechanism of action distinct from existing therapies. By combining these targeted treatments, there's potential for improved efficacy and durability of response, which is why researchers are hopeful about their impact on patient outcomes.

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

Research has shown that cilta-cel, a treatment studied in this trial for multiple myeloma, delivers strong results. Studies found that cilta-cel leads to a high rate of positive responses, with many patients experiencing long-term remission, meaning the cancer stays away, even in cases where other treatments have been extensively used. Talquetamab, another treatment option in this trial, has also shown promising results. Clinical trials reported significant response rates, with many participants maintaining their improvement for months. Both treatments show potential as effective options for managing multiple myeloma. ^{3 4 6 7 8}

Who Is on the Research Team?

Janssen Research & Development, LLC Clinical Trial

Principal Investigator

Janssen Research & Development, LLC

Are You a Good Fit for This Trial?

This trial is for individuals with newly diagnosed standard-risk multiple myeloma. Participants will initially receive a combination of Daratumumab, Bortezomib, Lenalidomide, and Dexamethasone before being tested with different sequences of cancer treatments including Cilta-cel, Talquetamab in combination with Daratumumab and Teclistamab in combination with Daratumumab.

Inclusion Criteria

My multiple myeloma is classified as stage I or II.

My blood or urine tests show signs of multiple myeloma.

I have been newly diagnosed with multiple myeloma.

Exclusion Criteria

My cancer has high-risk features according to specific genetic tests.

I am HIV positive.

I have or had brain or spinal cord involvement by my cancer.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Induction

Participants undergo apheresis followed by 4 cycles of DVRd induction

16 weeks

4 cycles (in-person)

Consolidation

Participants receive alternating cycles of Tal-D and Tec-D following cilta-cel infusion

672 days

8 cycles (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 5 years

What Are the Treatments Tested in This Trial?

Interventions

• Bortezomib
• Cilta-cel
• Daratumumab
• Dexamethasone
• Lenalidomide
• Talquetamab

Trial Overview The study tests the effectiveness of treatment sequences on achieving sustained minimal residual disease negativity (no detectable cancer cells) combined with complete response to therapy at 5 years post-treatment initiation. It also measures how long patients live without their disease worsening (progression-free survival).

How Is the Trial Designed?

Group I: Cohort B: DVRd Induction + Cilta-cel + Tal-D and Tec-D Consolidation Experimental Treatment 9 Interventions

Participants will undergo apheresis followed by 4 cycles of DVRd induction and Cilta-cel will be generated from the participants' T-cells selected from the apheresis product. Upon completion of cilta-cel production, product release and completion of induction, participants will begin consolidation with a conditioning regimen (cyclophosphamide and fludarabine daily for 3 days) with infusion of cilta-cel 5 to 7 days after the start of the conditioning regimen. Following cilta-cel infusion, alternating cycles of Tal-D (Cycle 1, 3, 5, and 7) and Tec-D (Cycle 2, 4, 6, and 8) will be started, no earlier than Day 84 and no later than Day 168 post cilta-cel infusion. Each cycle of Tal-D or Tec-D is 84 days which includes an extended treatment-free interval.

Group II: Cohort A: DVRd Induction + Tal-D Consolidation + Cilta-cel Experimental Treatment 8 Interventions

Participants will undergo apheresis followed by 4 cycles of DVRd induction (each cycle is of 28 days) and cilta-cel will be generated from the participants' T-cells selected from the apheresis product. Upon completion of cilta-cel production, product release, and completion of induction, participants will begin consolidation with 4 cycles of Tal-D (each cycle is of 28 days), followed by a conditioning regimen (cyclophosphamide and fludarabine daily for 3 days); cilta-cel will be administered 5 to 7 days after the start of the conditioning regimen.

Cilta-cel is already approved in United States, European Union for the following indications:

Approved in United States as Carvykti for:

• Relapsed or refractory multiple myeloma in adults who have received at least one prior line of therapy, including a proteasome inhibitor and an immunomodulatory agent, and are refractory to lenalidomide

Approved in European Union as Carvykti for:

• Relapsed and refractory multiple myeloma in adults who have received at least one prior line of therapy, including a proteasome inhibitor and an immunomodulatory agent, and are refractory to lenalidomide

Who Is Running the Clinical Trial?

Janssen Research & Development, LLC

Lead Sponsor

Trials

1,022

Recruited

6,408,000+

Joaquin Duato

Janssen Research & Development, LLC

Chief Executive Officer since 2022

MBA from ESADE, Master of International Management from Thunderbird School of Global Management

Dr. Jijo James, MD

Janssen Research & Development, LLC

Chief Medical Officer since 2014

MD from St. Johns Medical College, MPH from Columbia University

Published Research Related to This Trial

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) 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) therapy significantly improved health-related quality of life (HRQoL) in patients with relapsed/refractory multiple myeloma, with a notable decrease in reported symptoms such as pain and fatigue from 85.2% at baseline to 22.2% by Day 184.

The majority of patients (70.8%) felt that cilta-cel met or exceeded their treatment expectations, highlighting its efficacy and the positive impact of a long treatment-free period on their overall health perception.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Patient Perceptions Regarding Ciltacabtagene Autoleucel Treatment: Qualitative Evidence From Interviews With Patients With Relapsed/Refractory Multiple Myeloma in the CARTITUDE-1 Study. Cohen, AD., Hari, P., Htut, M., et al.[2023]

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) 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) 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) 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]

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 ... ... cilta-cel in real world setting demonstrates similar effectiveness to CARTITUDE-1 in the treatment of relapsed or refractory multiple myeloma.

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

Real-World Efficacy Outcomes of Ciltacabtagene ... Forty-five percent of RW patients did not meet the inclusion criteria for C-1. The overall response rate was lower in the RW group (88% vs. 97%, ...

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

Comparative Effectiveness of Ciltacabtagene Autoleucel in ... Introduction: Ciltacabtagene autoleucel (cilta-cel) is approved for relapsed or refractory multiple myeloma (RRMM). In the CARTITUDE-4 study ( ...

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. astctjournal.org astctjournal.org/article/S2666-6367(25)00354-9/fulltext

Freedomm: Fifth-Line or Later Real-World Evaluation of ... In this real-world study, patients treated with cilta-cel after 4+PL had favorable clinical outcomes, similar to the CARTITUDE-1 trial, with most remaining ...

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. hematology.org hematology.org/newsroom/press-releases/2024/cilta-cel-found-highly-effective-in-first-real-world-study

Cilta-cel Found Highly Effective in First Real-World Study Of 236 patients who received cilta-cel infusions at 16 US medical centers in 2022, 89% saw their cancer respond to the treatment and 70% had a complete ...