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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)

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ClinicalTrials.gov Identifier: NCT04133636
Recruitment Status : Not yet recruiting
First Posted : October 21, 2019
Last Update Posted : October 21, 2019
Sponsor:
Information provided by (Responsible Party):
Janssen Research & Development, LLC

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 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, 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. The overall duration of the study is up to 2.5 years.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 40 participants
Allocation: Non-Randomized
Intervention Model: Parallel 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
Estimated Study Start Date : October 23, 2019
Estimated Primary Completion Date : April 12, 2022
Estimated Study Completion Date : September 28, 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Multiple Myeloma

Arm Intervention/treatment
Experimental: Cohort A: Progressive Disease After 1-3 Prior Lines of Therapy
After lymphodepletion JNJ-68284528 will be administered as a single infusion.
Drug: 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).

Experimental: Cohort B: Early Relapse after Front-line Therapy
After lymphodepletion JNJ-68284528 will be administered as a single infusion.
Drug: 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).




Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. 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).

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. Maximum Blood Concentration (Cmax) of JNJ-68284528 [ Time Frame: Up to 1 year ]
    Cmax is defined as the maximum observed blood concentration.

  13. Time to Reach Maximum Observed Blood Concentration (Tmax) of JNJ-68284528 [ Time Frame: Up to 1 year ]
    Tmax is defined as actual sampling time to reach maximum observed blood concentration.

  14. Time to Last Quantifiable Blood Concentration (Tlast) of JNJ-68284528 [ Time Frame: Up to 1 year ]
    Tlast is defined as the time to last observed quantifiable blood concentration.

  15. Area Under the Blood Concentration-Time Curve from Time Zero to Last Quantifiable Time (AUClast) of JNJ-68284528 [ Time Frame: Up to 1 year ]
    The AUClast is the area under the blood concentration-time curve from time zero to last quantifiable time.

  16. Area Under the Blood Concentration-Time Curve from Time Zero to Infinite Time (AUCinfinity) of JNJ-68284528 [ Time Frame: Up to 1 year ]
    AUCinfinity is defined as area under the blood analyte concentration-time curve from time 0 to infinite time of JNJ-68284528.

  17. Rate Constant (Lambda[z]) [ Time Frame: Up to 1 year ]
    Lambda(z) is the first-order rate constant associated with the terminal portion of the curve, determined as the negative slope of the terminal log-linear phase of the drug concentration-time curve.

  18. Elimination Half-Life (t1/2) of JNJ-68284528 [ Time Frame: Up to 1 year ]
    t1/2 is defined as the time measured for the blood concentration to decrease by 1 half of its original concentration.

  19. Levels of B-Cell Maturation Antigen (BCMA) Expressing Cells and Soluble BCMA [ Time Frame: Up to 2 years ]
    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.

  20. Systemic Inflammatory Cytokine Concentrations [ Time Frame: Up to 2 years ]
    Blood cytokine concentrations (Interleukin [IL]-6, IL-15, IL-10, and Interferon [IFN-gamma]) will be measured for biomarker assessment.

  21. Levels of CAR-T Cell Activation Markers [ Time Frame: Up to 2 years ]
    CAR-T cell activation 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.

  22. Levels of JNJ-68284528 T Cell Expansion (proliferation), and Persistence [ Time Frame: Up to 2 years ]
    Levels of JNJ-68284528 T cell expansion (proliferation), and persistence via monitoring CAR-T positive cell counts and CAR transgene level will be reported.

  23. Number of Participants with Anti-JNJ-68284528 Antibodies [ Time Frame: Up to 2 years ]
    Number of participants exhibiting anti-drug antibodies for JNJ-68284528 will be reported.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Cohort A: Received from 1 to 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 (<) 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
  • 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
  • Eastern Cooperative Oncology Group (ECOG) performance status grade of 0 or 1

Exclusion Criteria:

  • Prior treatment with chimeric antigen receptor T (CAR-T) therapy directed at any target
  • Any therapy that is targeted to B-cell maturation antigen (BCMA)
  • 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 prior to apheresis
  • Known active, or prior history of central nervous system (CNS) involvement or exhibits clinical signs of meningeal involvement of multiple myeloma
  • Serious underlying medical condition, such as (a) evidence of serious active viral, bacterial, 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

Information from the National Library of Medicine

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


Contacts
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Contact: Study Contact 844-434-4210 JNJ.CT@sylogent.com

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Sponsors and Collaborators
Janssen Research & Development, LLC
Investigators
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Study Director: Janssen Research & Development, LLC Clinical Trial Janssen Research & Development, LLC

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Responsible Party: Janssen Research & Development, LLC
ClinicalTrials.gov Identifier: NCT04133636     History of Changes
Other Study ID Numbers: CR108581
2018-004124-10 ( EudraCT Number )
68284528MMY2003 ( Other Identifier: Janssen Research & Development, LLC )
First Posted: October 21, 2019    Key Record Dates
Last Update Posted: October 21, 2019
Last Verified: October 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description:

The data sharing policy of the Janssen Pharmaceutical Companies of Johnson & Johnson is available at www.janssen.com/clinical-trials/transparency.

As noted on this site, requests for access to the study data can be submitted through Yale Open Data Access (YODA) Project site at yoda.yale.edu

URL: https://www.janssen.com/clinical-trials/transparency

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases