VRd + CAR-T Therapy for Multiple Myeloma

(CARTITUDE-5 Trial)

Recruiting at 205 trial locations

Overseen By SparkCures Patient Support (US only)

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Janssen Research & Development, LLC

Must not be taking: BCMA therapy

Disqualifiers: Frailty, Neuropathy, CNS involvement, HIV, 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: 6 weeks for VRd cycles, followed by long-term Rd or Cilta-cel

743 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to compare the efficacy of Bortezomib, Lenalidomide and Dexamethasone (VRd) induction followed by a single administration of ciltacabtagene autoleucel (cilta-cel) versus VRd induction followed by Lenalidomide and Dexamethasone (Rd) maintenance in newly diagnosed multiple myeloma participants for whom ASCT is not planned as initial therapy in terms of Progression Free Survival (PFS).

Do I need to stop my current medications for the trial?

The trial information does not specify if 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 VRd + CAR-T therapy for multiple myeloma?

Research shows that combinations of bortezomib, lenalidomide, and dexamethasone (VRd) have improved response rates and prolonged response duration in multiple myeloma patients compared to older treatments. Additionally, lenalidomide plus dexamethasone has been effective in patients with relapsed multiple myeloma, even after several previous treatments. ^{1 2 3 4 5}

Is VRd + CAR-T Therapy for Multiple Myeloma safe for humans?

The combination of bortezomib (Velcade), lenalidomide (Revlimid), and dexamethasone (Decadron) has been studied in multiple myeloma patients and is generally well-tolerated, with common side effects including neuropathy (nerve damage), fatigue, and low blood cell counts. These treatments have been used safely in various studies, showing favorable safety profiles in humans. ^{1 2 6 7 8}

How is the VRd + CAR-T treatment for multiple myeloma different from other treatments?

The VRd + CAR-T treatment is unique because it combines the standard VRd drug regimen (bortezomib, lenalidomide, and dexamethasone) with CAR-T therapy, which uses modified immune cells to target cancer, offering a novel approach that may enhance treatment effectiveness compared to traditional drug combinations alone. ^{2 3 9 10 11}

Research Team

Janssen Research & Development, LLC Clinical Trial

Principal Investigator

Janssen Research & Development, LLC

Eligibility Criteria

This trial is for adults with newly diagnosed multiple myeloma who can't have high-dose chemo with stem cell transplant due to age or other health issues. They must have measurable disease, be in good physical condition (able to perform daily activities without help), and women able to bear children must test negative for pregnancy.

Inclusion Criteria

I am not a candidate for high-dose chemotherapy with stem cell transplant due to my age, health conditions, or it's not my first treatment choice.

I am a woman who can have children and have had 2 negative pregnancy tests before starting VRd treatment.

I am fully active or can carry out light work.

Exclusion Criteria

You have a frailty index score of 2 or higher based on the Myeloma Geriatric Assessment.

I have not received a live vaccine in the last 4 weeks.

I experience significant nerve pain or damage.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

4 weeks

Pre-randomization Treatment

Participants receive VRd regimen for 6 cycles before randomization

18 weeks

Multiple visits for each cycle

Treatment

Participants in Arm A receive 2 more cycles of VRd followed by Rd maintenance; Arm B undergoes apheresis, receives 2 more cycles of VRd, conditioning regimen, and Cilta-cel infusion

6 weeks for VRd cycles, followed by long-term Rd or Cilta-cel

Multiple visits for each cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 12 years and 5 months

Treatment Details

Interventions

• Bortezomib
• Cilta-cel
• Dexamethasone
• Lenalidomide

Trial Overview The study compares two treatments: one group receives VRd (Bortezomib, Lenalidomide, Dexamethasone) followed by a CAR-T therapy called cilta-cel; the other gets VRd followed by Rd (Lenalidomide and Dexamethasone). The main goal is to see which treatment better stops the cancer from progressing.

Participant Groups

Group I: Arm B: VRd+Ciltacabtagene Autoleucel (Cilta-cel) Experimental Treatment 6 Interventions

Participants will receive VRd regimen for 6 cycles before randomization. Following randomization, participants in Arm B will undergo apheresis and receive two more cycles of VRd as bridging therapy. In VRd treatment, participants will receive bortezomib 1.3 mg/m\^2 SC on Days 1, 4, 8 and 11 of each cycle for Cycles 1 to 8; oral lenalidomide 25 mg on days 1 to 14 of each cycle for Cycles 1 to 8 and oral dexamethasone 20 mg on days 1, 2, 4, 5, 8, 9, 11 and 12 of each cycle for Cycles 1 to 8. Each cycle will consist of 21 days. After 8 cycles of VRd, 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).

Group II: Arm A: VRd+Rd (Standard Therapy) Experimental Treatment 3 Interventions

Participants will receive bortezomib, lenalidomide, and dexamethasone (VRd) regimen for 6 cycles before randomization. Following randomization, participants in Arm A will receive 2 more cycles of VRd. In VRd treatment, participants will receive bortezomib 1.3 milligram per meter square (mg/m\^2) subcutaneously (SC) on Days 1, 4, 8 and 11 of each cycle (Cycles 1 to 8), oral lenalidomide 25 mg on Days 1 to 14 of each cycle (Cycles 1 to 8) and oral dexamethasone 20 mg on Days 1, 2, 4, 5, 8, 9, 11, and 12 of each cycle (Cycles 1 to 8). Each cycle will consist of 21 days. After 8 cycles of VRd, treatment will continue with lenalidomide and dexamethasone (Rd) maintenance therapy. In Rd treatment, participants will receive oral lenalidomide 25 mg on Days 1 to 21 of each cycle and oral dexamethasone 40 mg on Days 1, 8, 15, and 22 of each cycle. Each cycle will consist of 28 days. Participants will continue to receive Rd until confirmed progressive disease or unacceptable toxicity.

Bortezomib is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Velcade for:

• Multiple myeloma
• Mantle cell lymphoma

Approved in United States as Velcade for:

• Multiple myeloma
• Mantle cell lymphoma

Approved in Canada as Velcade for:

• Multiple myeloma
• Mantle cell lymphoma

Approved in Japan as Velcade for:

• Multiple myeloma
• Mantle cell lymphoma

Who Is Running the Clinical Trial?

Janssen Research & Development, LLC

Lead Sponsor

Trials

1,022

Recruited

6,408,000+

Giacomo Salvadore

Janssen Research & Development, LLC

Chief Medical Officer since 2023

MD from the University of Rome, Tor Vergata

Ricardo Attar

Janssen Research & Development, LLC

Chief Executive Officer since 2008

PhD in Molecular Biology from the University of Buenos Aires

Findings from Research

In a phase III study involving 155 multiple myeloma patients, bortezomib and lenalidomide treatments showed similar effectiveness, with 15% and 18% of patients achieving a very good partial response (VGPR) respectively, indicating comparable efficacy.

Both treatment regimens resulted in similar median progression-free survival (PFS) of 16.3 months for bortezomib and 18.6 months for lenalidomide, along with comparable two-year overall survival rates of 75% and 74%, confirming their safety and effectiveness in managing multiple myeloma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bortezomib, cyclophosphamide, dexamethasone versus lenalidomide, cyclophosphamide, dexamethasone in multiple myeloma patients at first relapse. Montefusco, V., Corso, A., Galli, M., et al.[2020]

In a study involving 98 relapsed refractory multiple myeloma patients, treatment with lenalidomide plus dexamethasone resulted in a 52% overall response rate, with 49% achieving partial remission and 3% achieving complete remission, despite patients having undergone a median of 5 prior treatments.

The combination therapy not only provided rapid responses but also extended overall survival by nearly six months, demonstrating its efficacy and safety regardless of previous treatments with thalidomide and bortezomib.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lenalidomide in relapsed refractory myeloma patients: impact of previous response to bortezomib and thalidomide on treatment efficacy. Results of a medical need program in Belgium. Delforge, M., Michiels, A., Doyen, C., et al.[2018]

The introduction of bortezomib and lenalidomide, especially in combination with dexamethasone, has significantly improved treatment outcomes for multiple myeloma, leading to better response rates and longer durations of response compared to older therapies.

Triplet regimens like lenalidomide, bortezomib, and dexamethasone (RVD) have shown enhanced efficacy and good tolerability in both newly diagnosed and relapsed/refractory multiple myeloma patients, indicating a promising approach for improving patient survival.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Treatment of multiple myeloma with lenalidomide and bortezomib combination therapy]. Takeda, Y., Sakaida, E., Nakaseko, C.[2018]

The combination treatment of bortezomib, pulsed dexamethasone, and weekly cyclophosphamide (CVD) resulted in a high overall response rate of 75% and a complete response rate of 31% in patients with relapsed/refractory myeloma, significantly outperforming other regimens.

The safety profiles of the CVD combination were similar to those of bortezomib/dexamethasone and bortezomib alone, with comparable rates of side effects like thrombocytopenia, neutropenia, and neuropathy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The combination of cyclophosphamide, velcade and dexamethasone induces high response rates with comparable toxicity to velcade alone and velcade plus dexamethasone. Davies, FE., Wu, P., Jenner, M., et al.[2022]

In a large observational study of 2150 patients with relapsed/refractory multiple myeloma, lenalidomide plus dexamethasone demonstrated a favorable safety profile, with lower incidence rates of neuropathy and infections compared to other treatments like bortezomib and thalidomide.

The study confirmed that lenalidomide's safety profile in a real-world setting is consistent with previous clinical trial data, with no new safety concerns identified, although it did show a higher incidence of neutropenia compared to bortezomib and thalidomide.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Noninterventional, Observational, European Post-Authorization Safety Study of Patients With Relapsed/Refractory Multiple Myeloma Treated With Lenalidomide. Gamberi, B., Berthou, C., Hernandez, M., et al.[2021]

References

1. England pubmed.ncbi.nlm.nih.gov

Bortezomib, cyclophosphamide, dexamethasone versus lenalidomide, cyclophosphamide, dexamethasone in multiple myeloma patients at first relapse. [2020]

2. Australia pubmed.ncbi.nlm.nih.gov

Peripheral blood stem cell mobilisation following bortezomib, lenalidomide and dexamethasone induction for multiple myeloma: a real-world single-centre experience. [2023]

3. England pubmed.ncbi.nlm.nih.gov

Upfront bortezomib, lenalidomide, and dexamethasone compared to bortezomib, cyclophosphamide, and dexamethasone in multiple myeloma. [2020]

4. England pubmed.ncbi.nlm.nih.gov

Lenalidomide in relapsed refractory myeloma patients: impact of previous response to bortezomib and thalidomide on treatment efficacy. Results of a medical need program in Belgium. [2018]

5. Japan pubmed.ncbi.nlm.nih.gov

[Treatment of multiple myeloma with lenalidomide and bortezomib combination therapy]. [2018]

6. Italy pubmed.ncbi.nlm.nih.gov

The combination of cyclophosphamide, velcade and dexamethasone induces high response rates with comparable toxicity to velcade alone and velcade plus dexamethasone. [2022]

7. United States pubmed.ncbi.nlm.nih.gov

Lenalidomide, bortezomib, and dexamethasone combination therapy in patients with newly diagnosed multiple myeloma. [2021]

8. United States pubmed.ncbi.nlm.nih.gov

A Noninterventional, Observational, European Post-Authorization Safety Study of Patients With Relapsed/Refractory Multiple Myeloma Treated With Lenalidomide. [2021]

9. Germany pubmed.ncbi.nlm.nih.gov

A phase II trial of small-dose bortezomib, lenalidomide and dexamethasone (sVRD) as consolidation/maintenance therapy in patients with multiple myeloma. [2018]

10. Switzerland pubmed.ncbi.nlm.nih.gov

Integrated analysis of randomized controlled trials evaluating bortezomib + lenalidomide + dexamethasone or bortezomib + thalidomide + dexamethasone induction in transplant-eligible newly diagnosed multiple myeloma. [2023]

11. United States pubmed.ncbi.nlm.nih.gov

Phase 1 Trial Evaluating Vorinostat Plus Bortezomib, Lenalidomide, and Dexamethasone in Patients With Newly Diagnosed Multiple Myeloma. [2021]