Combination Therapies for Multiple Myeloma
(aMMbition Trial)
Recruiting in Palo Alto (17 mi)
+8 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: Janssen Research & Development, LLC
Disqualifiers: Myelodysplastic syndrome, B-cell malignancy, others
No Placebo Group
Prior Safety Data
Breakthrough Therapy
Trial Summary
What is the purpose of this trial?The purpose of this study is to evaluate the rate of response (how effectively treatment is working) with signs of potential cure at 5 years after the start of induction treatment. This is defined as a composite of sustained (at least 2 years) minimal residual disease (MRD) negativity with complete response/stringent complete response (CR/sCR) and a positron emission tomography/computed tomography (PET/CT) scan that does not show any signs of cancer at 5 years. MRD negativity and CR/sCR is defined as no detectable signs of remaining cancer cells after the treatment. This study will also characterize how well the treatments administered work in the study through progression-free survival (PFS). PFS is defined as the length of time during and after the treatment of a disease, that a participant lives with the disease, but it does not get worse.
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.
What data supports the effectiveness of the treatment for multiple myeloma?
Research shows that ciltacabtagene autoleucel (cilta-cel), a type of CAR-T cell therapy, is effective in patients with multiple myeloma who have already tried other treatments. It has shown early, deep, and long-lasting responses, improving patients' quality of life.
12345Is ciltacabtagene autoleucel (cilta-cel) safe for humans?
Ciltacabtagene autoleucel (cilta-cel) has a tolerable safety profile for treating relapsed or refractory multiple myeloma, with adverse effects ranging from mild to life-threatening, but mostly manageable. It has shown a consistent safety profile over longer follow-up periods.
12467How is the treatment Cilta-cel unique for multiple myeloma?
Cilta-cel is a unique treatment for multiple myeloma because it is a CAR T-cell therapy that targets BCMA on cancer cells, using the patient's own modified T-cells to attack the cancer. It is known for inducing deep and long-lasting responses in patients who have already tried several other treatments, and it generally outperforms similar therapies in terms of effectiveness.
14568Eligibility Criteria
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.
+2 more
Exclusion Criteria
My cancer has high-risk features according to specific genetic tests.
I am HIV positive.
I do not have ongoing blood disorders or cancer, other than multiple myeloma, that needs treatment.
+4 more
Trial Timeline
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
Participant Groups
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).
2Treatment groups
Experimental Treatment
Group I: Cohort B: DVRd Induction + Cilta-cel + Tal-D and Tec-D ConsolidationExperimental Treatment9 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-celExperimental Treatment8 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
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
City of HopeDuarte, CA
University of Iowa Hospital and ClinicsIowa City, IA
University of California San FranciscoSan Francisco, CA
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Who Is Running the Clinical Trial?
Janssen Research & Development, LLCLead Sponsor
References
Comparison of Cilta-cel, an Anti-BCMA CAR-T Cell Therapy, Versus Conventional Treatment in Patients With Relapsed/Refractory Multiple Myeloma. [2022]In the single-arm, phase 1b/2 CARTITUDE-1 study, ciltacabtagene autoleucel (cilta-cel), an anti-B-cell maturation antigen chimeric antigen receptor T-cell (CAR-T) therapy, showed encouraging efficacy in US patients with multiple myeloma (MM) who previously received an immunomodulatory drug, proteasome inhibitor, and anti-CD38 monoclonal antibody (triple-class exposed).
Patient Perceptions Regarding Ciltacabtagene Autoleucel Treatment: Qualitative Evidence From Interviews With Patients With Relapsed/Refractory Multiple Myeloma in the CARTITUDE-1 Study. [2023]Ciltacabtagene autoleucel (cilta-cel), a novel chimeric antigen receptor T (CAR-T) cell therapy, has demonstrated early, deep, and durable clinical responses in heavily pretreated patients with relapsed/refractory multiple myeloma (RRMM), and improvements in health-related quality of life (HRQoL) in CARTITUDE-1 (NCT03548207). Patient perspectives on treatment provide context to efficacy outcomes and are an important aspect of therapeutic evaluation.
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]This study estimated the comparative efficacy of ciltacabtagene autoleucel (cilta-cel; CARTITUDE-1), a chimeric antigen receptor (CAR)-T-cell therapy, versus 3 non-CAR-T therapies (belantamab mafodotin [DREAMM-2], selinexor plus dexamethasone [STORM Part 2], and melphalan flufenamide plus dexamethasone [HORIZON]), each with distinct mechanisms of action, for the treatment of patients with relapsed or refractory multiple myeloma (RRMM) who were triple-class exposed to an immunomodulatory drug, proteasome inhibitor, and an anti-CD38 monoclonal antibody.
Ciltacabtagene autoleucel: The second anti-BCMA CAR T-cell therapeutic armamentarium of relapsed or refractory multiple myeloma. [2022]Ciltacabtagene autoleucel (also known as cilta-cel) is a chimeric antigen receptor (CAR) T-cell therapy that targets B-cell maturation antigen (BCMA) on the surface of cancer cells in B cell malignancies, such as multiple myeloma (MM). It is a second-generation CAR that is outfitted with an ectodomain comprising two BCMA-binding single chain variable fragment (ScFv) domains, a transmembrane domain, and an endodomain possessing CD3ζ and 4-1BB. Cilta-cel is an autologous, gene-edited CAR T-cell that is prepared by collecting and modifying the recipient's T-cells to create a patient personalized treatment in the laboratory to be infused back. This CAR T-cell product exceptionally entails CARs with two BCMA-targeting single-domain antibodies that detect two epitopes of BCMA expressed on the malignant cells of MM. Cilta-cel is the current addition to the treatment armamentarium of relapsed or refractory (r/r) MM after its approval by the FDA on February 28, 2022, based on the results of the Phase 1b/2 CARTITUDE-1 study. It was the second approved anti-BCMA CAR T-cell product after idecabtagene vicleucel (ide-cel) to treat myeloma patients. It induces early, deep, and long-lasting responses with a tolerable safety profile in r/r MM. Cilta-cel-treated myeloma patients may potentially experience adverse effects ranging from mild to life-threatening, but they are mostly manageable toxicities. Besides, it has a consistent safety profile upon a longer follow-up of patients. Cilta-cel generally outperforms ide cel in terms of efficacy in MM, but shows comparable adverse events. This review highlights the current updates on cilta-cel efficacy, adverse events, comparison with ide-cel, and its future direction in the treatment of MM.
Cilta-cel or Standard Care in Lenalidomide-Refractory Multiple Myeloma. [2023]Ciltacabtagene autoleucel (cilta-cel), a B-cell maturation antigen (BCMA)-directed CAR T-cell therapy, is effective in heavily pretreated patients with relapsed or refractory multiple myeloma. We investigated cilta-cel in earlier treatment lines in patients with lenalidomide-refractory disease.
Cilta-cel OK'd for Multiple Myeloma. [2022]The FDA has approved ciltacabtagene autoleucel (cilta-cel), a chimeric antigen receptor T-cell therapy targeting BCMA, as a fifth-line option for patients with relapsed/refractory multiple myeloma. Cilta-cel is the second agent in its class to get a regulatory thumbs-up in less than a year.
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]Ciltacabtagene autoleucel (cilta-cel) is a novel agent being investigated in the single-arm CARTITUDE-1 trial (NCT03548207) for patients with relapsed or refractory multiple myeloma who are triple-class exposed to an immunomodulatory drug, proteasome inhibitor, and an anti-CD38 monoclonal antibody. The objective of this study was to evaluate the comparative efficacy of cilta-cel vs physician's choice of treatment, as no head-to-head trials have been conducted.
Component Costs of CAR-T Therapy in Addition to Treatment Acquisition Costs in Patients with Multiple Myeloma. [2023]Label="INTRODUCTION" NlmCategory="BACKGROUND">Ciltacabtagene autoleucel (cilta-cel), is a B-cell maturation antigen-directed, genetically modified autologous chimeric antigen receptor T-cell (CAR-T) immunotherapy. It is indicated for treatment for adult patients with relapsed or refractory multiple myeloma (RRMM) after four or more prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody. The objective of this study was to estimate the per-patient US commercial healthcare costs related to cilta-cel (CARVYKTI®) CAR-T therapy (i.e., costs separate from cilta-cel therapy acquisition) for patients with RRMM.