VRd + CAR-T Therapy for Multiple Myeloma

(CARTITUDE-5 Trial)

Not currently recruiting at 231 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a combination of treatments for individuals newly diagnosed with multiple myeloma, a type of blood cancer, who do not plan to undergo a stem cell transplant. It compares two treatment paths: one involves a mix of drugs (bortezomib, lenalidomide, dexamethasone) followed by ongoing treatment, and the other adds a one-time dose of a special cell therapy (CAR-T therapy, specifically Cilta-cel) after the initial drug mix. The goal is to determine which option helps patients maintain disease stability for a longer period. This trial seeks participants diagnosed with multiple myeloma who are unable or not planning to undergo a stem cell transplant. As a Phase 3 trial, it represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

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.

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

A previous study found the VRd regimen, which includes bortezomib, lenalidomide, and dexamethasone, to be well-tolerated. Serious side effects were rare, and no treatment-related deaths occurred. Another study showed a low risk of blood clots, around 6%.

For ciltacabtagene autoleucel (cilta-cel), research indicates it is generally safe for individuals with relapsed or refractory multiple myeloma. Approved for use in 2022, its safety has been well-studied. Most patients responded well to the treatment, though some side effects can occur, as is common with many cancer therapies.

This trial is in phase 3, meaning the treatment has already been tested in earlier stages, helping ensure its safety for further study. ^{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 incorporate innovative approaches like CAR-T cell therapy. Unlike traditional treatments that often focus on chemotherapy alone, the investigational treatment in Arm B uses ciltacabtagene autoleucel (Cilta-cel), which involves reprogramming a patient's own T cells to better target and attack the cancer. This personalized, targeted approach could potentially offer a more effective way to combat multiple myeloma, especially for patients who haven't responded well to existing therapies. Additionally, combining the standard VRd regimen with these advanced techniques aims to enhance overall treatment efficacy and long-term outcomes.

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

Research has shown that a treatment combination called VRd, which includes bortezomib, lenalidomide, and dexamethasone, is commonly used for multiple myeloma and effectively slows the disease. In this trial, participants in Arm A will receive VRd followed by maintenance therapy with lenalidomide and dexamethasone. Arm B will explore adding cilta-cel to VRd. In a real-world study, 89% of patients who received cilta-cel experienced cancer improvement, and 70% achieved a complete response, meaning their cancer became undetectable. This suggests that cilta-cel is highly effective, especially for patients who have tried other treatments. Overall, these treatments show promise in helping patients live longer without disease progression. ^{5 6 7 8 9}

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 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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

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

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]

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]

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]

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. carvyktihcp.com carvyktihcp.com/cartitude-4-efficacy/

CARTITUDE-4 Study - CARVYKTI® (ciltacabtagene autoleucel) Discover the efficacy outcomes for the primary and follow-up analysis of the CARVYKTI® CARTITUDE-4 study, including study design, survival results, ...

4. 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 ...

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

Comparative Effectiveness of Ciltacabtagene Autoleucel in ... These data highlight the value of cilta-cel as an effective therapy in earlier-line patients with relapsed, lenalidomide-refractory MM exposed ...

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 ... SOC cilta-cel in RRMM results in deep and durable response despite over half the patients not meeting the CARTITUDE-1 eligibility criteria.

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. 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).

9. multiplemyelomahub.com multiplemyelomahub.com/medical-information/real-world-data-on-the-safety-and-efficacy-of-cilta-cel-in-patients-with-rrmm

Real-world data on the safety and efficacy of cilta-cel in ... We summarize results from a retrospective analysis assessing the safety and efficacy of ciltacabtagene autoleucel in a real-world population ...