CARTITUDE-2: 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

• Sponsor: Janssen Research & Development, LLC (Industry)
• Overall Status: Recruiting
• CT.gov ID: NCT04133636
• Collaborator: (none)
• Enrollment: 157
• Locations: 43
• Arm: 1
• Anticipated Duration (Months): 75.6
• Patients Per Site: 3.7
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate the overall minimal residual disease (MRD) negative rate of participants who receive JNJ-68284528.

Condition or Disease	Intervention/Treatment	Phase
Multiple Myeloma	Drug: JNJ-68284528; Drug: Lenalidomide; Drug: Daratumumab; Drug: Bortezomib; Drug: Dexamethasone	Phase 2

Detailed Description

Multiple myeloma is characterized by the production of monoclonal immunoglobulin (Ig) proteins or protein fragments (M proteins) that have lost their function. The main aim of the study is to determine the safety and efficacy of JNJ-68284528 in various clinical settings. JNJ-68284528 is an autologous chimeric antigen receptor T-cell (CAR-T) therapy that targets B-cell maturation antigen (BCMA). The study comprises of a Screening Phase (less than or equal to [<=] 28 days prior to apheresis) followed by Apheresis (will occur upon enrollment); a Treatment Phase including a conditioning regimen followed by infusion of JNJ-68284528 and post-infusion assessments from Day 1 to Day 100 (participants who receive an infusion of JNJ-68284528 should continue all subsequent assessments); and a Post-treatment Phase (Day 101 and up to the end of each study cohort). Safety evaluations will include a review of adverse events, laboratory test results, vital sign measurements, physical examination findings (including neurologic examination), assessment of cardiac function, immune effector cell-associated encephalopathy (ICE) score, handwriting assessment, and assessment of Eastern Cooperative Oncology Group (ECOG) performance status grade. Efficacy evaluations will include measurements of tumor burden/residual disease, myeloma proteins, bone marrow examinations, skeletal surveys, extramedullary plasmacytomas, and serum calcium corrected for albumin. For certain participants (those without measurable disease in serum or urine) efficacy will be assessed via imaging: positron emission tomography/ computed tomography (PET/CT) or whole body magnetic resonance imaging (MRI). The overall duration of the study is up to 2.5 years.

Study Design

• Study Type: Interventional
• Anticipated Enrollment: 157 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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: Nov 7, 2019
• Anticipated Primary Completion Date: Aug 1, 2024
• Anticipated Study Completion Date: Feb 25, 2026

Arms and Interventions

Arm

Intervention/Treatment

Experimental: JNJ-68284528 Single group assignment-After lymphodepletion, JNJ-68284528 will be administered as 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 PI, IMiD, anti-CD38, and anti- BCMA therapy), cohort D (Less than CR after ASCT front-line therapy; some participants will be administered JNJ-68284528 followed by lenalidomide), cohort F (Newly diagnosed multiple myeloma [NDMM] with standard risk [international staging system {ISS} Stage I and II] and after initiation of therapy). Participants in cohort E (NDMM, 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 consolidation regimen of lenalidomide.

Drug: JNJ-68284528; Participants in cohort A,B,C, D, E and F will receive JNJ-68284528 intravenously.; Other Names: Ciltacabtagene autoleucel (cilta-cel) ; Drug: Lenalidomide; Some participants in cohort D and all participants in cohort E will also receive lenalidomide capsules orally.; Drug: Daratumumab; Participants in cohort E will also receive daratumumab subcutaneous (SC) injection.; Drug: Bortezomib; Participants in cohort E will also receive bortezomib subcutaneously.; Drug: Dexamethasone; Participants in cohort E will also receive dexamethasone orally or intravenously.

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants with Negative Minimal Residual Disease (MRD) [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.

Secondary Outcome Measures

1. Overall Response Rate (ORR) [Up to 2 years and 6 months]

   ORR is defined as the percentage of participants who achieve a partial response (PR) or better according to the IMWG criteria.

2. VGPR or Better Rate [Up to 2 years and 6 months]

   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.

3. Clinical Benefit Rate (CBR) [Up to 2 years and 6 months]

   CBR is defined as the percentage of participants who achieve ORR (sCR + CR + VGPR + PR) + minimal response (MR) according to the IMWG criteria.

4. Duration of Response (DOR) [Up to 2 years and 6 months]

   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.

5. Time to Response (TTR) [Up to 2 years and 6 months]

   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.

6. MRD Negative Rate at 12 Months for Participants who Achieve a Complete Response (CR) [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.

7. Time to MRD Negativity [Up to 2 years and 6 months]

   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.

8. Duration of MRD Negativity [Up to 2 years and 6 months]

   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).

9. MRD Negative Rate Across Clinical Response [Up to 2 years and 6 months]

   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.

10. Number of Participants with Adverse Events by Severity [Up to 2 years and 6 months]

    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.

11. Number of Participants with Adverse Events (AE) as a Measure of Safety and Tolerability [Up to 2 years and 6 months]

    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.

12. Number of Participants with Laboratory Abnormalities [Up to 2 years and 6 months]

    Number of participants with laboratory abnormalities will be reported.

13. Number of Participants with Vital Sign Abnormalities [Up to 2 years and 6 months]

    Number of participants with vital sign abnormalities will be reported.

14. Levels of B-Cell Maturation Antigen (BCMA) Expressing Cells and Soluble BCMA [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.

15. Systemic Inflammatory Cytokine Concentrations [Up to 1 year]

    Blood cytokine concentrations (Interleukin [IL]-6, IL-15, IL-10, and Interferon [IFN-gamma]) will be measured for biomarker assessment.

16. Levels of JNJ-68284528 T Cell Expansion (proliferation), and Persistence [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.

17. Number of Participants with Anti-JNJ-68284528 Antibodies [Up to 1 year]

    Number of participants exhibiting anti-drug antibodies for JNJ-68284528 will be reported.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Cohort A: Received a minimum of 1 to a maximum of 3 prior lines of therapy including a proteasome inhibitor (PI) and immunomodulatory therapy (IMiD), and lenalidomide refractory per International Myeloma Working Group (IMWG) guidelines

• Cohort B: Received one line of prior therapy including a PI and an IMiD, and disease progression per IMWG criteria less than or equal to (<=) 12 months after treatment with autologous stem cell transplantation (ASCT) or <=12 months from the start of anti-myeloma therapy for participants who have not had an ASCT

• Cohort C: Previously treated with a PI, an IMiD, an anti-CD38 monoclonal antibody and B-cell maturation antigen (BCMA)-directed therapy

• Cohort D: Newly diagnosed multiple myeloma per IMWG with a history of 4 to 8 total cycles of initial therapy, including induction, high-dose therapy, and ASCT with or without consolidation

• Cohort E: Have newly diagnosed multiple myeloma without prior therapy (one cycle of prior therapy before enrollment is acceptable) and classified as high risk defined as either: 1) International Staging System (ISS) stage III criteria, Beta 2 microglobulin greater than or equal to (>=) 5.5 milligram per liter (mg/L) (via local or central laboratory assessment) or 2) high risk cytogenetic features del(17/17p), t (14;16), t(14;20), 1q amplification (at least 4 total copies) in at least 20 percent (%) of the total plasma cell population

• Cohort F:

• Participant must have a documented efficacy response of very good partial response (VGPR) or better, without progressive disease prior to enrollment, as assessed per IMWG 2016 criteria

• Received initial therapy as specified below. The dose/schedule of cycles administered will be as per standard of care. It is acceptable for up to 1 cycle of the protocol-specified regimens to be missing one of the listed agents (example, held due to toxicity). Acceptable combinations include: At least 5 to 8 cycles of initial therapy with daratumumab, bortezomib, lenalidomide and dexamethasone (D-VRd). The dose/schedule of cycles administered will be as per standard of care or; at least 4 to 8 cycles of initial therapy with daratumumab, lenalidomide and dexamethasone (D-Rd) or; at least 4 to 8 cycles of initial therapy with a carfilzomib-based triplet or quadruplet regimen

• Cohorts A, B, C, E:

• Serum monoclonal paraprotein (M-protein) level greater than or equal to (>=) 1.0 gram per deciliter (g/dL) or urine M-protein level >=200 milligram (mg)/24 hours

• Light chain multiple myeloma in whom only measurable disease is by serum free light chain (FLC) levels in the serum: Serum immunoglobulin FLC >=10 mg/dL and abnormal serum immunoglobulin kappa lambda FLC ratio

• Cohort A: For participants with neither serum nor urine measurable disease, baseline positron emission tomography/ computed tomography (PET/CT) or whole -body magnetic resonance imaging (MRI) may be used to satisfy the measurable disease criteria. A minimum of one lesion with a bi-dimensional measurement of at least 1 centimeter (cm)*1 cm is required

• Cohorts B, C: For participants with neither serum nor urine measurable disease, baseline positron emission tomography/ computed tomography (PET/CT) or whole body magnetic resonance imaging (MRI) may be used to satisfy the measurable disease criteria

• Cohorts A, B, C, D, E, F: Eastern Cooperative Oncology Group (ECOG) performance status grade of 0 or 1

Exclusion Criteria:

• Cohorts A, B, D, F: Any therapy that is targeted to BCMA

• Cohorts A, B, C, D, F: Prior treatment with chimeric antigen receptor T (CAR-T) therapy directed at any target

• Cohorts A, B, C, D, F:

• Ongoing toxicity from previous anticancer therapy must resolve to baseline levels or to Grade 1 or less except for alopecia or peripheral neuropathy

• Received a cumulative dose of corticosteroids equivalent to >=70 mg of prednisone within the 7 days (Cohort A, B, C, F) or 14 days (Cohort D) prior to apheresis

• Serious underlying medical condition, such as (a) evidence of active viral or bacterial infection requiring systemic antimicrobial therapy, or uncontrolled systemic fungal infection; (b) active autoimmune disease or a history of autoimmune disease within 3 years; (c) overt clinical evidence of dementia or altered mental status; (d) any history of Parkinson's disease or other neurodegenerative disorder

• Cohorts A, B, C, D, E, F: Known active, or prior history of central nervous system (CNS) involvement or exhibits clinical signs of meningeal involvement of multiple myeloma

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	City Of Hope Med Ctr	Duarte	California	United States	91010
2	University of California, San Francisco	San Francisco	California	United States	94143
3	Moffitt Cancer Center	Tampa	Florida	United States	33612
4	Emory University	Atlanta	Georgia	United States	30322
5	Northwestern University	Chicago	Illinois	United States	60611
6	University of Chicago	Chicago	Illinois	United States	60637
7	Indiana University	Indianapolis	Indiana	United States	46202
8	Johns Hopkins	Baltimore	Maryland	United States	21287
9	Dana-Farber Cancer Institute	Boston	Massachusetts	United States	02115
10	Mayo Clinic Rochester	Rochester	Minnesota	United States	55905
11	Washington University School of Medicine	Saint Louis	Missouri	United States	63110
12	Hackensack University Medical Center	Hackensack	New Jersey	United States	07601
13	Rutgers Cancer Institute of New Jersey	New Brunswick	New Jersey	United States	08903
14	Montefiore Medical Center	Bronx	New York	United States	10467
15	Roswell Park Cancer Institute	Buffalo	New York	United States	14263
16	Mount Sinai Medical Center	New York	New York	United States	10029
17	Memorial Sloan-Kettering Cancer Center	New York	New York	United States	10065
18	Levine Cancer Institute, Carolinas HealthCare System	Charlotte	North Carolina	United States	28204
19	University of Pennsylvania	Philadelphia	Pennsylvania	United States	19104
20	University of Pittsburgh	Pittsburgh	Pennsylvania	United States	15232
21	Baylor University Medical Center	Dallas	Texas	United States	75246
22	University of Texas, MD Anderson Cancer Center	Houston	Texas	United States	77030
23	Fred Hutchinson Cancer Center	Seattle	Washington	United States	98109
24	Universitair Ziekenhuis - Antwerpen	Antwerp		Belgium	2650
25	Institut Jules Bordet	Brussel		Belgium	1000
26	UZ Gent	Gent		Belgium	9000
27	UZ Leuven	Leuven		Belgium	3000
28	CHRU de Lille - Hôpital Claude Huriez	Lille		France	59037
29	C.H.U. Hotel Dieu - France	Nantes		France	44093
30	Hopital Saint-Louis	Paris cedex 10		France	75475
31	Universitatsklinikum Carl Gustvav Carus Dresden an der Technischen Universitat Dresden	Dresden		Germany	01307
32	Universitaetsklinikum Hamburg Eppendorf	Hamburg		Germany	20246
33	Universitaetsklinikum Heidelberg	Heidelberg		Germany	69120
34	Universitatsklinikum Leipzig	Leipzig		Germany	04103
35	Klinikum der Eberhard-Karls-Universität/Abt. für innere Med. II/Hämatologie/Onkologie-Germany	Tübingen		Germany	72076
36	Universitätsklinikum Würzburg	Würzburg		Germany	97080
37	Sheba Medical Center Tel Hashomer	Ramat Gan		Israel	52621
38	Tel-Aviv Sourasky Medical Center	Tel-Aviv		Israel	64239
39	VU Medisch Centrum	Amsterdam		Netherlands	1081 HV
40	University Medical Center Groningen	Groningen		Netherlands	9713 GZ
41	King Faisal Specialist Hospital & Research Center	Riyadh		Saudi Arabia	11211
42	Clinica Univ. de Navarra	Pamplona		Spain	31008
43	Hosp. Clinico Univ. de Salamanca	Salamanca		Spain	37007

Sponsors and Collaborators

• Janssen Research & Development, LLC

Investigators

• Study Director: Janssen Research & Development, LLC Clinical Trial, Janssen Research & Development, LLC

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Janssen Research & Development, LLC
• ClinicalTrials.gov Identifier: NCT04133636
• Other Study ID Numbers: CR108581; 2018-004124-10; 68284528MMY2003
• First Posted: Oct 21, 2019
• Last Update Posted: Aug 12, 2022
• Last Verified: Aug 1, 2022

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Janssen Research & Development, LLC: Cellular Therapy; CAR-T Therapy; BCMA CAR-T
• Additional relevant MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell; Dexamethasone; Lenalidomide; Bortezomib; Daratumumab

Study Results

No Results Posted as of Aug 12, 2022