What is the mechanism of action of this treatment?

Multiple Myeloma treatments target the disease through various mechanisms. Daratumumab is a monoclonal antibody that targets CD38 on myeloma cells, leading to cell death. Bortezomib is a proteasome inhibitor that disrupts protein degradation, causing apoptosis in myeloma cells. Lenalidomide is an immunomodulatory drug that enhances immune response against myeloma cells and inhibits their growth. Dexamethasone is a corticosteroid that reduces inflammation and has direct anti-myeloma effects. Ciltacabtagene Autoleucel (CAR-T cell therapy) targets BCMA on myeloma cells, using modified T-cells to recognize and kill these cells. These treatments are crucial as they address different pathways in myeloma cell survival and proliferation, offering a comprehensive approach to managing the disease.

What side effects are associated with this type of intervention?

Common treatments for Multiple Myeloma, particularly those involving CAR-T cell therapy like Ciltacabtagene Autoleucel, include a range of side effects. These can include cytokine release syndrome (CRS), which manifests as fever, fatigue, and hypotension, and neurotoxicity, which can lead to confusion, headaches, and seizures. Other side effects may include infections due to immunosuppression, cytopenias (low blood cell counts), and infusion-related reactions. Additionally, patients may experience gastrointestinal symptoms such as nausea, vomiting, and diarrhea, as well as general fatigue and muscle pain.

What prior FDA approvals exist?

The FDA has approved several treatments for Multiple Myeloma, including CAR-T cell therapies and other related drugs. Notably, CAR-T cell therapies such as idecabtagene vicleucel (Abecma) and ciltacabtagene autoleucel (Carvykti) target BCMA (B-cell maturation antigen) and have shown efficacy in treating relapsed or refractory Multiple Myeloma. Additionally, drugs like daratumumab (Darzalex), a monoclonal antibody targeting CD38, and bortezomib (Velcade), a proteasome inhibitor, have been approved and are commonly used in combination regimens for Multiple Myeloma treatment. These therapies represent significant advancements in the management of the disease.

What other types of research exist?

Promising alternatives to Ciltacabtagene Autoleucel for Multiple Myeloma patients include other CAR-T cell therapies such as Idecabtagene Vicleucel (another BCMA-targeting CAR-T therapy), and novel drug combinations like Daratumumab, Bortezomib, Lenalidomide, and Dexamethasone (DVRd). Additionally, bispecific antibodies targeting BCMA and T-cell engagers are emerging as potential treatments.

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Protein Degradation Enhancer

DVRd + Ciltacabtagene Autoleucel / ASCT for Multiple Myeloma (CARTITUDE-6 Trial)

Phase 3

Recruiting

Research Sponsored by Stichting European Myeloma Network

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

ECOG performance status of grade 0 or 1

Participants with documented NDMM according to IMWG diagnostic criteria, for whom high-dose therapy and ASCT are part of the intended initial treatment plan

Must not have

Known active, or prior history of central nervous system (CNS) involvement or clinical signs of meningeal involvement of MM

Received or plans to receive any live, attenuated vaccine (except for COVID-19 vaccines) within 4 weeks prior to randomization

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 10 years ( or 300 pfs events)

Awards & highlights

All Individual Drugs Already Approved

No Placebo-Only Group

Pivotal Trial

Approved for 60 Other Conditions

Summary

This trial is testing a combination of four drugs followed by either a special cell therapy or a stem cell transplant in newly diagnosed multiple myeloma patients who can have a transplant. The drugs fight cancer and boost immunity, while the cell therapy reprograms immune cells to attack cancer, and the stem cell transplant rebuilds bone marrow.

Who is the study for?

This trial is for newly diagnosed multiple myeloma patients who have measurable disease, are in good physical condition (ECOG grade 0 or 1), and have normal lab values. It's not open to those who've had CAR-T therapy, BCMA target therapy, other MM treatments except corticosteroids, strong CYP3A4 inducers recently, live vaccines within a month (except COVID-19 vaccine), or CNS involvement by MM.

What is being tested?

The study compares two approaches: one group receives Daratumumab with Bortezomib, Lenalidomide and Dexamethasone followed by a cell-based gene therapy called Ciltacabtagene Autoleucel; the other follows the same initial treatment but then has an Autologous Stem Cell Transplant instead.

What are the potential side effects?

Possible side effects include immune system reactions from Daratumumab and Cilta-cel therapies such as infusion reactions and infections. Chemotherapy drugs like Bortezomib may cause nerve damage while Lenalidomide can affect blood counts. Dexamethasone might lead to increased blood sugar levels.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I am fully active or restricted in physically strenuous activity but can do light work.

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I have newly diagnosed multiple myeloma and plan to undergo high-dose therapy and stem cell transplant.

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My cancer can be measured by specific protein levels in my blood or urine.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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My cancer has affected or previously affected my brain or spinal cord.

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I have not had any live vaccines (other than COVID-19) in the last 4 weeks.

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I have received treatments targeting BCMA before.

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I have only used corticosteroids briefly for my myeloma.

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I have previously undergone CAR-T cell therapy.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 10 years ( or 300 pfs events)

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 10 years ( or 300 pfs events)

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 10 years ( or 300 pfs events) for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Progression free survival (PFS)

Sustained MRD-negative CR

Secondary study objectives

Change from Baseline in Health-Related Quality of Life (HRQoL) as Assessed by European Organization for Research and Treatment of Cancer Quality-of-life Questionnaire Core 30 (EORTC-QLQ-C30) Scale Score

Change from Baseline in Health-Related Quality of Life as Assessed by European Quality of Life - 5 Dimensions-5 Levels (EQ-5D-5L) Scale Scor

Change from Baseline in Health-Related Quality of Life as Assessed by MySIm-Q Scale Score

+8 more

Awards & Highlights

All Individual Drugs Already Approved

Therapies where all constituent drugs have already been approved are likely to have better-understood side effect profiles.

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Pivotal Trial

The final step before approval, pivotal trials feature drugs that have already shown basic safety & efficacy.

Approved for 60 Other Conditions

This treatment demonstrated efficacy for 60 other conditions.

Trial Design

2Treatment groups

Experimental Treatment

Active Control

Group I: Arm B: DVRd followed by Ciltacabtagene AutoleucelExperimental Treatment7 Interventions

Participants will receive daratumumab, bortezomib, lenalidomide and dexamethasone (DVRd) for 6 induction cycles. Participants will receive a conditioning regimen (cyclophosphamide 300 mg/m\^2 intravenous \[IV\] and fludarabine 30 mg/m\^2 IV daily for 3 days) and Cilta-cel infusion 0.75\*10\^6 chimeric antigen receptor (CAR)-positive viable T cells/kilogram (kg), followed by lenalidomide post CAR-T cell therapy for 2 years Daratumumab subcutaneously (SC), 1800 mg on days 1, 8, 15 and 22 of cycle 1 and 2, on days 1 and 15 of cycle 3-6. Bortezomib SC 1.3 mg/m\^2 on days 1, 4, 8, and 11 of each cycle 1-6. Lenalidomide orally, 25 mg on days 1 to 21 of each cycle 1-6. Dexamethasone orally, 40 mg once a week on days 1, 8, 15 and 22 of each cycle 1-6. Each cycle will consist of 28 days. Lenalidomide maintenance orally 10 to 15 mg on days 1 to 28 (continuously) until confirmed progressive disease or unacceptable toxicity or for a maximum of 2 years

Group II: Arm A: DVRd + ASCT+DVRd (Standard Therapy)Active Control4 Interventions

Participants will receive daratumumab, bortezomib, lenalidomide and dexamethasone (DVRd) for 4 induction cycles. Followed by ASCT and 2 cycles of DVRd consolidation, and lenalidomide maintenance therapy for 2 years Daratumumab subcutaneously (SC), 1800 mg on days 1, 8, 15 and 22 of cycle 1 and 2, on days 1 and 15 of cycle 3-6. Bortezomib SC 1.3 mg/m\^2 on days 1, 4, 8, and 11 of each cycle 1-6. Lenalidomide orally, 25 mg on days 1 to 21 of each cycle 1-6. Dexamethasone orally, 40 mg once a week on days 1, 8, 15 and 22 of each cycle 1-6. Each cycle will consist 28 days. Lenalidomide maintenance orally 10 to 15 mg on days 1 to 28 (continuously) until confirmed progressive disease or unacceptable toxicity or for a maximum of 2 years

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Bortezomib

FDA approved

Dexamethasone

FDA approved

Lenalidomide

FDA approved

Ciltacabtagene autoleucel

FDA approved

Fludarabine

FDA approved

Daratumumab

FDA approved

Cyclophosphamide

FDA approved

0 / 8Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Multiple Myeloma treatments target the disease through various mechanisms. Daratumumab is a monoclonal antibody that targets CD38 on myeloma cells, leading to cell death. Bortezomib is a proteasome inhibitor that disrupts protein degradation, causing apoptosis in myeloma cells. Lenalidomide is an immunomodulatory drug that enhances immune response against myeloma cells and inhibits their growth. Dexamethasone is a corticosteroid that reduces inflammation and has direct anti-myeloma effects. Ciltacabtagene Autoleucel (CAR-T cell therapy) targets BCMA on myeloma cells, using modified T-cells to recognize and kill these cells. These treatments are crucial as they address different pathways in myeloma cell survival and proliferation, offering a comprehensive approach to managing the disease.