CAR-T Therapy for Multiple Myeloma

(CARTITUDE-2 Trial)

Recruiting at 53 trial locations

Overseen By SparkCures Patient Support (US only)

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Janssen Research & Development, LLC

Must not be taking: Corticosteroids, BCMA-targeted, CAR-T

Disqualifiers: Active infections, Autoimmune, CNS involvement, 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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 1 day for infusion, followed by monitoring

237 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a promising new treatment, JNJ-68284528 (also known as CAR-T therapy), for individuals with multiple myeloma, a type of blood cancer. The goal is to determine how often the treatment reduces cancer to very low levels, known as minimal residual disease (MRD) negativity. The trial includes several groups, such as those who have experienced a relapse or early progression after other treatments and those newly diagnosed. It might be suitable for individuals with multiple myeloma who have experienced progression or relapse after certain treatments. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, it mentions that ongoing toxicity from previous anticancer therapy must resolve to baseline levels or to Grade 1 or less, which might imply adjustments to your current treatment. It's best to discuss your specific medications with the trial coordinators.

Is there any evidence suggesting that JNJ-68284528 is likely to be safe for humans?

Research has shown that JNJ-68284528, also known as cilta-cel, has been tested for safety and effectiveness in treating multiple myeloma, a type of blood cancer. In some studies, about 89% of patients responded well to the treatment, and 70% saw their cancer completely disappear. This suggests the treatment can be very effective for many people.

However, safety remains a crucial consideration. Cilta-cel received approval in 2022 for patients whose multiple myeloma has returned, indicating it met safety standards for that condition. In clinical trials, some patients experienced side effects, such as fatigue, low blood cell counts, and infections. While the treatment is generally well-tolerated, risks can accompany any medical treatment.

Overall, cilta-cel has demonstrated both effectiveness and relative safety for patients with multiple myeloma, based on current studies and its approval for similar conditions. Discussing potential risks and benefits with healthcare providers is always advisable. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for multiple myeloma?

Researchers are excited about JNJ-68284528 for multiple myeloma because it represents a cutting-edge approach known as CAR-T cell therapy. Unlike traditional treatments like proteasome inhibitors or immunomodulatory drugs, which often require ongoing administration, JNJ-68284528 involves a single infusion that reprograms a patient's own T cells to target and destroy cancer cells. This personalized therapy holds the promise of long-lasting remission by precisely attacking myeloma cells, even in patients who have not responded to multiple prior treatments. Moreover, it offers hope for those with high-risk or newly diagnosed cases, potentially transforming treatment outcomes.

What evidence suggests that JNJ-68284528 might be an effective treatment for multiple myeloma?

Studies have shown that JNJ-68284528, also known as cilta-cel, holds promise for treating multiple myeloma, a type of blood cancer. Research indicates that about 89% of patients treated with cilta-cel experienced a positive response, and 70% achieved complete remission, with no signs of cancer detected. In some long-term studies, one-third of patients remained free from disease progression for at least five years. These results suggest that cilta-cel could potentially become a new standard treatment for multiple myeloma. The treatment has demonstrated better outcomes compared to other common treatments. Participants in this trial will receive a single infusion of JNJ-68284528, with some cohorts receiving additional treatments such as lenalidomide or a quadruplet induction regimen. ^{1 3 4 6 7}

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 multiple myeloma patients with varying treatment histories. Some must have tried specific therapies and be refractory to lenalidomide, while others may be newly diagnosed or ineligible for certain treatments due to age or comorbidities. Participants need a measurable level of disease and should be in good physical condition (ECOG grade 0-1).

Inclusion Criteria

I've had 1-3 treatments for my condition, including specific therapies, and one didn't work as expected.

I have newly diagnosed multiple myeloma and have undergone 4 to 8 cycles of initial treatment.

I am not a candidate for high-dose chemotherapy with stem cell transplant due to age, health issues, or personal choice.

Exclusion Criteria

My multiple myeloma has affected or previously affected my brain or spinal cord.

You have a serious medical condition such as active infection needing strong antibiotics, uncontrolled fungal infection, active autoimmune disease, recent history of autoimmune disease, dementia, Parkinson's disease, or other brain disorders.

I have no active cancers except for certain treated or low-risk cases.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Lymphodepletion

Participants undergo lymphodepletion prior to receiving JNJ-68284528 infusion

1 week

Treatment

Participants receive a single infusion of JNJ-68284528, with some cohorts receiving additional treatments such as lenalidomide

1 day for infusion, followed by monitoring

Follow-up

Participants are monitored for safety, effectiveness, and MRD status after treatment

Up to 2 years and 6 months

Open-label extension (optional)

Participants may continue to be monitored or receive additional treatment based on their response and MRD status

Long-term

What Are the Treatments Tested in This Trial?

Interventions

• JNJ-68284528

Trial Overview The study tests JNJ-68284528, a CAR-T therapy targeting BCMA, alongside other drugs like dexamethasone, lenalidomide, daratumumab, and bortezomib. It aims to assess the rate at which participants achieve minimal residual disease negativity.

How Is the Trial Designed?

Group I: JNJ-68284528 Experimental Treatment 5 Interventions

Single group assignment-Post lymphodepletion, JNJ-68284528 single infusion given to Part A participants: Cohort A(Progressive disease post 1-3 prior lines of therapy), Cohort B(Early relapse post front-line), Cohort C(Relapsed/refractory multiple myeloma post PI, IMiD,anti-CD38,anti-BCMA therapy), Cohort D(Less than CR post ASCT front-line therapy, some participants will receive JNJ-68284528 then lenalidomide), Cohort F(Newly diagnosed multiple myeloma \[NDMM\], standard risk \[International Staging System Stage I/II\] and post initial therapy); Cohort E(NDMM,transplant not planned,high risk disease) will first receive quadruplet induction regimen of daratumumab,bortezomib,lenalidomide and dexamethasone(D-VRd) then lymphodepletion and JNJ-68284528 then consolidation regimen of lenalidomide. Part B:Cohort G(NDMM,transplant not planned) will receive daratumumab, lenalidomide and dexamethasone followed by cilta-cel; Cohort H(NDMM,transplant-eligible) will receive D-VRd followed by cilta-cel.

JNJ-68284528 is already approved in United States, European Union for the following indications:

Approved in United States as Carvykti for:

• Relapsed or refractory multiple myeloma after one or more prior lines 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

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 phase 2 study of cilta-cel (CAR T cells targeting B-cell maturation antigen) in Japanese patients with relapsed/refractory multiple myeloma, the overall response rate was an impressive 100% among those receiving the target dose, with 87.5% achieving a very good partial response or better.

While 88.9% of patients experienced grade 3 or 4 adverse events and cytokine release syndrome, no neurotoxicity was reported, indicating a positive benefit/risk profile for cilta-cel in this heavily pretreated patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ciltacabtagene autoleucel in patients with relapsed/refractory multiple myeloma: CARTITUDE-1 (phase 2) Japanese cohort. Ri, M., Suzuki, K., Ishida, T., et al.[2022]

In a sub-analysis of the KarMMa trial involving 9 Japanese patients with relapsed/refractory multiple myeloma, idecabtagene vicleucel (ide-cel) demonstrated a high overall response rate of 89%, with 56% achieving a stringent complete response.

The treatment had a manageable safety profile, with all patients experiencing mild cytokine release syndrome and only one case of grade 2 neurotoxicity, indicating that ide-cel is both effective and tolerable for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 2 results of idecabtagene vicleucel (ide-cel, bb2121) in Japanese patients with relapsed and refractory multiple myeloma. Minakata, D., Ishida, T., Ando, K., et al.[2023]

CAR T cell therapy, particularly targeting B cell maturation antigen (BCMA), has shown promising efficacy in early clinical trials for treating multiple myeloma, indicating its potential as a new treatment option.

Recent research has also demonstrated that CAR T cells targeting activated integrin β7 can effectively eliminate multiple myeloma cells, including specific B cell types, and preparations for a clinical trial are underway.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chimeric antigen receptor T cell therapy for multiple myeloma. Hasegawa, K., Hosen, N.[2020]

The study developed dual-split CAR T cells targeting CD38 and CD138, which effectively killed multiple myeloma cells while sparing healthy cells, demonstrating a promising approach for enhancing specificity in CAR T-cell therapy.

The optimal combination of a low-affinity CD138sCAR and a high-affinity CD38cCAR showed effective anti-multiple myeloma activity in vivo, even against cells from patients previously treated with daratumumab, indicating potential for broader application in resistant cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Specific Targeting of Multiple Myeloma by Dual Split-signaling Chimeric Antigen Receptor T cells Directed against CD38 and CD138. van der Schans, JJ., Wang, Z., van Arkel, J., et al.[2023]

Ciltacabtagene autoleucel (cilta-cel), a BCMA-directed CAR T-cell therapy, has shown deep and durable response rates in patients with multiple myeloma who have undergone multiple lines of treatment, indicating its effectiveness even in heavily pretreated cases.

The review highlights the notable adverse events associated with cilta-cel and discusses ongoing studies that may change how multiple myeloma is managed in the future, emphasizing the therapy's potential impact on treatment paradigms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ciltacabtagene autoleucel for the treatment of multiple myeloma. Holstein, SA.[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) 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]

Chimeric antigen receptor (CAR) T-cell therapy shows great promise for treating relapsed/refractory multiple myeloma (RRMM), building on its success in other blood cancers like acute lymphocytic leukemia and diffuse large B-cell lymphoma.

The review highlights six potential target antigens for CAR T-cell therapy in multiple myeloma and discusses the safety profiles of existing CAR T-cell treatments, indicating a significant advancement in the management of this challenging disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current advances in chimeric antigen receptor T-cell therapy for refractory/relapsed multiple myeloma. Huang, H., Wu, HW., Hu, YX.[2020]

Chimeric antigen receptor (CAR)-modified T cell therapy has shown promising efficacy in treating refractory or relapsed multiple myeloma (MM) in both preclinical and clinical studies, indicating a potential new treatment avenue for this incurable disease.

The toxicities associated with CAR-T cell therapy are manageable, suggesting that this innovative approach could be a safe option for patients with MM, especially as research continues to identify effective targets and improve technologies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chimeric antigen receptor T cell therapies for multiple myeloma. Wu, C., Zhang, L., Brockman, QR., et al.[2020]

In a study of 203 patients with multiple myeloma, those previously treated with BCMA-targeted therapies had lower response rates and shorter durations of response when treated with idecabtagene vicleucel (ide-cel) compared to those without prior BCMA treatment.

Despite the lower efficacy in patients with prior BCMA therapy, ide-cel still produced meaningful clinical responses, particularly in patients who had received anti-BCMA CAR T therapy, indicating that sequential BCMA-targeted treatments can still be beneficial.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-world experience of patients with multiple myeloma receiving ide-cel after a prior BCMA-targeted therapy. Ferreri, CJ., Hildebrandt, MAT., Hashmi, H., et al.[2023]

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. jnj.com jnj.com/media-center/press-releases/single-infusion-of-carvykti-ciltacabtagene-autoleucel-delivered-lasting-treatment-free-remissions-for-at-least-five-years-in-patients-with-relapsed-or-refractory-multiple-myeloma

Single infusion of CARVYKTI® (ciltacabtagene autoleucel) ... New long-term CARTITUDE-1 data show one-third of patients treated with CARVYKTI® remain progression-free

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39162049/

Efficacy of CARVYKTI in CARTITUDE-4 versus other ... Conclusion: Cilta-cel demonstrated benefit over other common treatment regimens, highlighting its potential to become a new standard of care ...

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

Real-World Efficacy Outcomes of Ciltacabtagene ... We performed a retrospective analysis of adult patients diagnosed with RRMM who received cilta-cel to evaluate its efficacy in the RW setting.

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/39365257/

Safety and efficacy of standard-of-care ciltacabtagene ... Overall and complete response rates were as follows: all patients who received cilta-cel (N = 236), 89% and 70%; patients receiving conforming ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT03548207

NCT03548207 | A Study of JNJ-68284528, a Chimeric ... This study will evaluate the safety and efficacy of JNJ-68284528. The study will include two phases. In Phase1b the study will enroll adults with multiple ...

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

CARTITUDE-4 Study - CARVYKTI® (ciltacabtagene autoleucel) CARTITUDE-4 is a randomized, open label, multicenter controlled study in adult patients with relapsed and lenalidomide-refractory multiple myeloma.