CARTITUDE-1: A Study of JNJ-68284528, a Chimeric Antigen Receptor T Cell (CAR-T) Therapy Directed Against B-Cell Maturation Antigen (BCMA) in Participants With Relapsed or Refractory Multiple Myeloma

Sponsor
Janssen Research & Development, LLC (Industry)
Overall Status
Active, not recruiting
CT.gov ID
NCT03548207
Collaborator
(none)
126
Enrollment
21
Locations
1
Arm
49.4
Anticipated Duration (Months)
6
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of the study is to characterize safety of JNJ-68284528 and establish the recommended Phase 2 dose (RP2D) (Phase 1b) and to evaluate the efficacy of JNJ-68284528 (Phase 2).

Condition or DiseaseIntervention/TreatmentPhase
  • Biological: JNJ-68284528
Phase 1/Phase 2

Detailed Description

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 myeloma with interval assessments for potential dose escalation or de-escalation in subsequent participants. The dose selected at the completion of phase 1b will be used in Phase 2. Following consent, enrolled participants will undergo an apheresis procedure to collect cells for manufacture of investigational drug product (JNJ-68284528). Following manufacture of the drug product, participants will undergo lymphodepletion prior to infusion of JNJ-68284528. Participants will be followed for at least 2 years after study drug infusion, with long-term 15 year follow-up on a separate study. The study will evaluate safety, biomarkers, pharmacokinetic/pharmacodynamic evaluations and efficacy.

Study Design

Study Type:
Interventional
Actual Enrollment :
126 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase 1b-2, Open-Label Study of JNJ-68284528, A Chimeric Antigen Receptor T-Cell (CAR-T) Therapy Directed Against BCMA in Subjects With Relapsed or Refractory Multiple Myeloma
Actual Study Start Date :
Jun 29, 2018
Anticipated Primary Completion Date :
Feb 24, 2022
Anticipated Study Completion Date :
Aug 11, 2022

Arms and Interventions

ArmIntervention/Treatment
Experimental: JNJ-68284528

After lymphodepletion JNJ-68284528 will be administered as a single infusion.

Biological: JNJ-68284528
JNJ-68284528 consist of autologous T lymphocytes transduced with LCAR-B38M, a lentiviral vector to express a chimeric antigen receptor targeting the human B cell maturation antigen (anti-BCMA CAR).

Outcome Measures

Primary Outcome Measures

  1. Phase 1b: Number of Participants with Adverse Events [Minimum 2 years after JNJ-68284528 infusion (Day 1)]

    An adverse event 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.

  2. Phase 1b: Number of Participants with Adverse Events by Severity [Minimum 2 years after JNJ-68284528 infusion (Day 1)]

    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 should be evaluated according to the American Society for Transplantation and Cellular Therapy (ASTCT) consensus grading.

  3. Phase 2: Overall Response Rate (ORR) [Minimum 2 years after JNJ-68284528 infusion (Day 1)]

    The ORR is defined as the proportion of participants who achieve partial response (PR) or better according to International Myeloma Working Group (IMWG) criteria as assessed by the Independent Review Committee (IRC).

Secondary Outcome Measures

  1. Phase 2: Number of Participants with Adverse Events [Minimum 2 years after JNJ-68284528 infusion (Day 1)]

    An adverse event 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.

  2. Levels of B-Cell Maturation Antigen (BCMA) Expressing Cells and Soluble BCMA [Minimum 2 years after JNJ-68284528 infusion (Day 1)]

    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.

  3. Systemic Cytokine Concentrations [Minimum 2 years after JNJ-68284528 infusion (Day 1)]

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

  4. Levels of CAR-T Cells [Minimum 2 years after JNJ-68284528 infusion (Day 1)]

    CAR-T cells markers including, but not limited to, CD4+, CD8+, CD25+, central memory, effector memory cells will be reported. An evaluation of cell populations may be performed by flow cytometry or cytometry by time of flight (CyTOF) or both and correlated with response.

  5. Level of JNJ-68284528 T Cell Expansion (proliferation), and Persistence [Minimum 2 years after JNJ-68284528 infusion (Day 1)]

    Levels of JNJ-68284528 T cell expansion (proliferation), and persistence via monitoring CAR-T positive cell counts and CAR transgene level will be reported.

  6. Number of Participants with Anti-JNJ-68284528 Antibodies [Minimum 2 years after JNJ-68284528 infusion (Day 1)]

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

  7. Very Good Partial Response (VGPR) or Better Rate [Minimum 2 years after JNJ-68284528 infusion (Day 1)]

    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. IMWG criteria for VGPR: Serum and urine M-component detectable by immunofixation but not on electrophoresis, or greater than equal to (>=) 90 percent (%) reduction in serum M-protein plus urine M-protein less than (<) 100 milligram (mg)/24 hours, CR: Negative immunofixation on the serum and urine, disappearance of any soft tissue plasmacytomas and <5% plasma cells (PCs) in bone marrow. sCR: CR plus normal free light chain (FLC) ratio, and absence of clonal PCs by immunohistochemistry (IHC), immunofluorescencea or 2- to 4 color flow cytometry.

  8. Percentage of Participants who Achieve Clinical Benefit Rate [Minimum 2 years after JNJ-68284528 infusion (Day 1)]

    Clinical benefit rate is the CR + VGPR + PR + minimal response [MR] based on IMWG defined response criteria.

  9. Duration of Response (DOR) [Minimum 2 years after JNJ-68284528 infusion (Day 1)]

    DOR will be calculated among responders (with a PR or better response) from the date of initial documentation of a response (PR or better) to the date of first documented evidence of progressive disease, as defined in the IMWG criteria.

  10. Progression-free Survival (PFS) [Minimum 2 years after JNJ-68284528 infusion (Day 1)]

    PFS defined as time from date of initial infusion of JNJ-68284528 to date of first documented disease progression, or death due to any cause, whichever occurs first. IMWG criteria for PD: Increase of 25% from lowest response value in anyone of following: Serum M-component (absolute increase must be >=0.5 gram per deciliter (g/dL), Urine M-component (absolute increase must be >=200 mg/24 hours), Participants without measurable serum and urine M-protein levels: difference between involved and uninvolved FLC levels (absolute increase must be >10 milligrams per deciliter (mg/dL), participants without measurable serum and urine M-protein levels and without measurable disease by FLC levels, bone marrow PC% (absolute percentage must be >=10%), definite development of new bone lesions or soft tissue plasmacytomas or increase in size of bone lesions or tissue plasmacytomas.

  11. Overall Survival (OS) [Minimum 2 years after JNJ-68284528 infusion (Day 1)]

    OS is measured from the date of the initial infusion of JNJ-68284528 to the date of the participant's death.

  12. Percentage of Participants With Negative Minimal Residual Disease (MRD) [Minimum 2 years after JNJ-68284528 infusion (Day 1)]

    MRD negative rate is defined as the proportion of participants who achieve MRD negative status by the respective time point. MRD negativity will be evaluated as a potential surrogate for PFS and OS in multiple myeloma treatment.

  13. Time to Response (TTR) [Minimum 2 years after JNJ-68284528 infusion (Day 1)]

    TTR is defined as the time between date of the initial infusion of JNJ-68284528 and the first efficacy evaluation that the participant has met all criteria for PR or better.

  14. Change from Baseline in Health-related Quality of Life (HRQoL) as Measured by EORTC QLQ-C30 [Baseline up to study completion (Minimum 2 years after JNJ-68284528 Infusion on Day 1)]

    HRQoL will be assessed by the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core-30 (QLQ-C30) items. Subscale and single item scores are reported on a 0-100 scale with higher scores representing better global health status, better functioning, and worst symptoms.

  15. Change from Baseline in HRQoL as Measured by EORTC QLQ-MY20 [Baseline up to study completion (Minimum 2 years after JNJ-68284528 Infusion on Day 1)]

    HRQoL will be assessed by the EORTC QLQ-Multiple Myeloma ((MY20) module items. Subscale and single item scores are reported on a 0-100 scale with higher scores representing better global health status, better functioning, and worst symptoms.

  16. Change from Baseline in Participant-reported Health Status Measured by EQ-5D-5L [Baseline up to study completion (Minimum 2 years after JNJ-68284528 Infusion on Day 1)]

    Participant-reported health status measured by the EuroQol Group 5-dimension, 5-level (EQ-5D-5L) questionnaire. A total utility score is reported based on the health status, ranging from 0 to 1, where higher values indicate better health utility. The visual analog scale ranges from 0 to 100 where higher values indicate better overall health status.

  17. Change from Baseline in Global Health Status Using PGIC Scale [Baseline up to study completion (Minimum 2 years after JNJ-68284528 Infusion on Day 1)]

    Global health status as measured by the Patient Global Impression of Change (PGIC) scale in overall health. The PGIC is a single verbal rating scale ranging from 1 = a lot better now to 7 = a lot worse now.

  18. Change from Baseline in Pain Measured by PGIS Scale [Baseline up to study completion (Minimum 2 years after JNJ-68284528 Infusion on Day 1)]

    Participant reported pain measured by Patient Global Impression of Severity (PGIS) Scale. The PGIS is a single item to assess pain severity. The 5-point verbal rating scale ranged from 1 (none) to 5 (very severe).

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
  • Have documented diagnosis of multiple myeloma according to International Myeloma Working Group (IMWG) diagnostic criteria

  • Have measurable disease at Screening as defined by any of the following a) Serum monoclonal paraprotein (M-protein) level more than or equal to (>=) 1.0 gram per deciliter(g/dL) or urine M-protein level >=200 milligram per 24 hours (mg/24hr); or b)

Light chain multiple myeloma without measurable disease in the serum or the urine:

Serum immunoglobulin free light chain 10 mg/dL and abnormal serum immunoglobulin kappa lambda free light chain ratio

  • Have received at least 3 prior multiple myeloma treatment lines of therapy or are double refractory to an immunomodulatory drug (IMiD) and proteasome inhibitor (PI) (refractory multiple myeloma as defined by IMWG consensus criteria). Note: induction with or without hematopoietic stem cell transplant and with or without maintenance therapy is considered a single lines of therapy a) Undergone at least 1 complete cycle of treatment for each line of therapy, unless progressive disease (PD) was the best response to the regimen

  • Have received as part of previous therapy a PI, an IMiD, and an anti-CD38 antibody

  • Participant must have documented evidence of progressive disease based on investigator's determination of response by the IMWG criteria on or within 12 months of their last line of therapy. Confirmation may be from either central or local testing. Also, participants with documented evidence of progressive disease (as above) within the previous 6 months and who are refractory or non-responsive to their most recent line of therapy afterwards are eligible

  • Have Eastern Cooperative Oncology Group (ECOG) Performance Status grade of 0 or 1

Exclusion Criteria:
  • Have received prior treatment with chimeric antigen receptor T (CAR-T) therapy directed at any target

  • Have received any therapy that is targeted to B-cell maturation antigen (BCMA)

  • Have following cardiac conditions: a) New York Heart Association (NYHA) stage III or IV congestive heart failure b) Myocardial infarction or coronary artery bypass graft (CABG) less than or equal to (<=) 6 months prior to enrollment c) History of clinically significant ventricular arrhythmia or unexplained syncope, not believed to be vasovagal in nature or due to dehydration d) History of severe non-ischemic cardiomyopathy e) Impaired cardiac function (left ventricular ejection fraction [LVEF] less than [<]45%) as assessed by echocardiogram or multiple-gated acquisition (MUGA) scan (performed less than or equal to (<=) 8 weeks of apheresis)

  • Received a cumulative dose of corticosteroids equivalent to >= 70 mg of prednisone within the 7 days prior to apheresis

  • Have received either of the following: a) An allogenic stem cell transplant within 6 months before apheresis. Participants who received an allogeneic transplant must be off all immunosuppressive medications for 6 weeks without signs of graft-versus-host disease (GVHD) b) An autologous stem cell transplant less than or equal to (<=) 12 weeks before apheresis

  • Have 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

SiteCityStateCountryPostal Code
1Mayo Clinic Cancer Center-ScottsdalePhoenixArizonaUnited States85054
2City of HopeDuarteCaliforniaUnited States91010
3University of California, San FranciscoSan FranciscoCaliforniaUnited States94143
4University of ChicagoChicagoIllinoisUnited States60637
5Dana-Farber Cancer InstituteBostonMassachusettsUnited States02115
6Beth Israel Deaconess Medical CenterBostonMassachusettsUnited States02215
7Massachusetts General HospitalBostonMassachusettsUnited States02215
8Barbara Ann Karmanos Cancer InstituteDetroitMichiganUnited States48201
9Mayo Clinic RochesterRochesterMinnesotaUnited States55902
10University of Nebraska Medical CenterOmahaNebraskaUnited States68198
11Mount Sinai Medical CenterNew YorkNew YorkUnited States10029
12Memorial Sloan Kettering Cancer CenterNew YorkNew YorkUnited States10065
13Levine Cancer InstituteCharlotteNorth CarolinaUnited States28204
14University of PennsylvaniaPhiladelphiaPennsylvaniaUnited States19104
15University of Pittsburgh Medical CenterPittsburghPennsylvaniaUnited States15232
16Sarah Cannon Research InstituteNashvilleTennesseeUnited States37203
17Froedtert MemorialMilwaukeeWisconsinUnited States53226
18University Hospital Kyoto Perfectural University of MedicineKyotoJapan602-8566
19Nagoya City University HospitalNagoyaJapan467-8602
20Hokkaido University HospitalSapporo-shiJapan060-8648
21Japanese Red Cross Medical CenterShibuyaJapan150-8935

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:
NCT03548207
Other Study ID Numbers:
  • CR108480
  • 2018-000121-32
  • 68284528MMY2001
First Posted:
Jun 7, 2018
Last Update Posted:
Oct 8, 2021
Last Verified:
Oct 1, 2021
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Additional relevant MeSH terms:

Study Results

No Results Posted as of Oct 8, 2021