A Study of JNJ-68284528, a Chimeric Antigen Receptor T Cell (CAR-T) Therapy Directed Against B-cell Maturation Antigen (BCMA) in Participants With Multiple Myeloma (CARTITUDE-2)
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT04133636|
Recruitment Status : Recruiting
First Posted : October 21, 2019
Last Update Posted : March 26, 2021
|Condition or disease||Intervention/treatment||Phase|
|Multiple Myeloma||Drug: JNJ-68284528 Drug: Lenalidomide Drug: Daratumumab Drug: Bortezomib Drug: Dexamethasone||Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||120 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase 2, Multicohort Open-Label Study of JNJ-68284528, a Chimeric Antigen Receptor T Cell (CAR-T) Therapy Directed Against BCMA in Subjects With Multiple Myeloma|
|Actual Study Start Date :||November 7, 2019|
|Estimated Primary Completion Date :||April 12, 2022|
|Estimated Study Completion Date :||August 15, 2024|
Single group assignment- After lymphodepletion, JNJ-68284528 will be administered as a single infusion to participants in cohort A (Progressive disease after 1-3 prior lines of therapy), cohort B (Early relapse after front-line), cohort C (Relapsed/refractory multiple myeloma after proteasome inhibitor [PI], immunomodulatory [IMiD], anti-CD38, and anti-B-cell maturation antigen [BCMA] therapy) and cohort D (Less than CR after autologous stem cell transplantation [ASCT] front-line therapy; some participants will be administered JNJ-68284528 followed by lenalidomide). Participants in cohort E (Newly diagnosed multiple myeloma, transplant not planned, high risk disease) will first be administered with quadruplet induction regimen of daratumumab, bortezomib, lenalidomide and dexamethasone (D-VRd), followed by lymphodepletion and JNJ-68284528, followed by a consolidation regimen of daratumumab and lenalidomide (D+R).
Participants in cohort A,B,C, D and E will receive JNJ-68284528 intravenously.
Some participants in cohort D and all participants in cohort E will also receive lenalidomide capsules orally.
Participants in cohort E will also receive daratumumab subcutaneous (SC) injection.
Participants in cohort E will also receive bortezomib subcutaneously.
Participants in cohort E will also receive dexamethasone orally or intravenously.
- Percentage of Participants with Negative Minimal Residual Disease (MRD) [ Time Frame: At least 1 year after JNJ-68284528 infusion on Day 1 ]MRD negative rate is the percentage of participants who achieve MRD negative status by evaluation of bone marrow aspirate as defined by the International Myeloma Working Group (IMWG) criteria.
- Overall Response Rate (ORR) [ Time Frame: Up to 2 years ]ORR is defined as the percentage of participants who achieve a partial response (PR) or better according to the IMWG criteria.
- VGPR or Better Rate [ Time Frame: Up to 2 years ]The VGPR or better rate (stringent complete responses [sCR] + complete response [CR] + VGPR), defined as the percentage of participants achieving VGPR or better response according to IMWG criteria during or after the study treatment.
- Clinical Benefit Rate (CBR) [ Time Frame: Up to 2 years ]CBR is defined as the percentage of participants who achieve ORR (sCR + CR + VGPR + PR) + minimal response (MR) according to the IMWG criteria.
- Duration of Response (DOR) [ Time Frame: Up to 2 years ]DOR will be calculated among responders from the date of initial documentation of a response (PR or better) to the date of first documented evidence of progressive disease according to the IMWG criteria.
- Time to Response (TTR) [ Time Frame: Up to 2 years ]TTR is defined as the time from the date of the initial infusion of JNJ-68284528 and the first efficacy evaluation that the participant has met all criteria for PR or better.
- MRD Negative Rate at 12 Months for Participants who Achieve a Complete Response (CR) [ Time Frame: 12 months ]MRD negative rate at 12 months for participants who achieved a complete response (CR) is defined as the percentage of participants who are MRD negative by bone marrow aspirate and meet the IMWG criteria for CR at 12 months after initial dose of JNJ-68284528 and before disease progression or starting subsequent therapy including retreatment of JNJ-68284528.
- Time to MRD Negativity [ Time Frame: Up to 2 years ]Time to MRD negativity will be calculated in participants who are MRD negative by bone marrow aspirate from the date of the initial infusion of JNJ-68284528 to the initial date of reaching the MRD negative status.
- Duration of MRD Negativity [ Time Frame: Up to 2 years ]Duration of MRD negativity will be calculated among participants who are MRD negative by bone marrow aspirate from the date of initial MRD negativity to the date when MRD is detected at the same threshold (10^-5).
- MRD Negative Rate Across Clinical Response [ Time Frame: Up to 2 years ]MRD negative rate across clinical response groups will be assessed for all participants who achieved a complete response (CR) or stringent complete response (sCR) or very good partial response (VGPR) according to the IMWG criteria during or after the study treatment. MRD negative rate is defined as the percentage of participants who have negative MRD by bone marrow aspirate at any timepoint.
- Number of Participants with Adverse Events by Severity [ Time Frame: Up to 2 years ]An assessment of severity grade will be made according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), with the exception of cytokine release syndrome (CRS), and immune effector cell-associated neurotoxicity syndrome (ICANS). CRS and ICANS will be evaluated according to the American Society for Transplantation and Cellular Therapy (ASTCT) consensus grading.
- Number of Participants with Adverse Events (AE) as a Measure of Safety and Tolerability [ Time Frame: Up to 2 years ]An AE is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product.
- Number of Participants with Laboratory Abnormalities [ Time Frame: Up to 2 years ]Number of participants with laboratory abnormalities will be reported.
- Number of Participants with Vital Sign Abnormalities [ Time Frame: Up to 2 years ]Number of participants with vital sign abnormalities will be reported.
- Levels of B-Cell Maturation Antigen (BCMA) Expressing Cells and Soluble BCMA [ Time Frame: Up to 1 year ]Levels of expression of BCMA-expressing plasma cells in the bone marrow as well as the level of soluble BCMA in blood will be reported.
- Systemic Inflammatory Cytokine Concentrations [ Time Frame: Up to 1 year ]Blood cytokine concentrations (Interleukin [IL]-6, IL-15, IL-10, and Interferon [IFN-gamma]) will be measured for biomarker assessment.
- Levels of JNJ-68284528 T Cell Expansion (proliferation), and Persistence [ Time Frame: Up to 1 year ]Levels of JNJ-68284528 T cell expansion (proliferation), and persistence via monitoring CAR-T positive cell counts and CAR transgene level will be reported.
- Number of Participants with Anti-JNJ-68284528 Antibodies [ Time Frame: Up to 1 year ]Number of participants exhibiting anti-drug antibodies for JNJ-68284528 will be reported.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04133636
|Contact: Study Contact||844-434-4210||JNJ.CT@sylogent.com|
|Study Director:||Janssen Research & Development, LLC Clinical Trial||Janssen Research & Development, LLC|