A Study of JNJ-68284528 Out-of-Specification (OOS) for Commercial Release in Participants With Multiple Myeloma

A Safety and Efficacy Study of JNJ-68284528 (Ciltacabtagene Autoleucel) Out-of-Specification (OOS) for Commercial Release in Patients With Multiple Myeloma

The purpose of this study is to evaluate the efficacy and safety of cilta-cel out-of-specification (OOS).

Study Overview

• Status: Completed
• Conditions: Multiple Myeloma
• Intervention / Treatment: Drug: Cilta-cel; Drug: Lymphodepleting Therapy (Cyclophosphamide and Fludarabine)

• Study Type: Interventional
• Enrollment (Actual): 86
• Phase: Phase 2

Expanded Access

Available outside the clinical trial. See expanded access record.

Contacts and Locations

• Study Contact: Name: Study Contact; Phone Number: 844-434-4210; Email: Participate-In-This-Study@its.jnj.com

Study Locations

• United States
  • California
    • Duarte, California, United States, 91010
      • City of Hope
    • San Francisco, California, United States, 94143
      • University of California San Francisco
    • Stanford, California, United States, 94305
      • Stanford University Medical Center
  • Colorado
    • Denver, Colorado, United States, 80218
      • Colorado Blood Cancer Institute
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory University
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern University
  • Kansas
    • Westwood, Kansas, United States, 66205
      • Kansas University Medical Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Dana-Farber Cancer Institute
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Barbara Ann Karmanos Cancer Institute
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University School of Medicine
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
      • Hackensack University Medical Center
  • New York
    • New York, New York, United States, 10065
      • Memorial Sloan Kettering Cancer Center
    • New York, New York, United States, 10029
      • Mount Sinai Medical Center
  • North Carolina
    • Charlotte, North Carolina, United States, 28204
      • Levine Cancer Institute
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15232
      • University of Pittsburgh Medical Center
  • Texas
    • Houston, Texas, United States, 77030
      • MD Anderson Cancer Center
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Medical College of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Eligible for treatment with cilta-cel per United States prescribing information (USPI) or locally approved label
• Participant is suffering from serious or life threatening multiple myeloma per USPI (or locally approved label, respectively), and re-apheresis, re-manufacturing, or other anti-myeloma directed therapies is not considered feasible or adequate per investigator
• Has adequate general health status and organ function per investigator assessment and meets the criteria to receive cilta-cel out-of-specifications (OOS)
• Meets the criteria to receive lymphodepleting chemotherapy
• A woman of childbearing potential must have a negative highly sensitive serum (beta-human chorionic gonadotropin [beta-hCG]) pregnancy test during screening and prior to the first dose of cyclophosphamide and fludarabine

Exclusion Criteria:

• History of active uncontrolled infection or condition where an administration of cilta-cel OOS constitutes serious health risk to the participant
• Known allergies, hypersensitivity, or intolerance to the excipients of cilta-cel OOS including dimethyl sulfoxide (DMSO), dextran 40, or residual kanamycin per USPI
• Hepatitis B infection
• Hepatitis C infection defined as (anti hepatitis C virus [HCV] antibody positive or detectable HCV ribonucleic acid [RNA]) or known to have a history of hepatitis C
• Seropositive for human immunodeficiency virus (HIV)
• Uncontrolled autoimmune disease

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Ciltacabtagene Autoleucel (Cilta-cel); Eligible participants will receive bridging therapy (that is, anti-plasma cell directed treatment) based on participant's clinical status and timing of availability of cilta-cel (JNJ-68284528) along with lymphodepleting chemotherapy (cyclophosphamide 300 milligrams per meter square [mg/m^2] intravenous [IV] and fludarabine 30 mg/m^2 IV daily, for 3 days). After 5 to 7 days of initiating lymphodepleting chemotherapy, participants will receive a single IV infusion of cilta-cel (JNJ-68284528) at a total targeted dose of 0.75*10^6 chimeric antigen receptor (CAR)-positive viable T cells per kilogram (cells/kg).

Drug: Cilta-cel; Cilta-cel will be administered as an IV infusion.; Other Names: JNJ-68284528; Drug: Lymphodepleting Therapy (Cyclophosphamide and Fludarabine); Lymphodepleting therapy (cyclophosphamide and fludarabine) will be administered intravenously.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Response Rate (ORR)	ORR is defined as percentage of participants who achieve partial response or better according to international myeloma working group (IMWG) response criteria.	Screening Phase through End of Study (EOS) (Up to 4 years)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants with Treatment-emergent Adverse Events (TEAEs)	Treatment-emergent adverse events (TEAEs) are defined as AEs with onset or worsening on or after date of first dose of study treatment.	Up to 4 years
Number of Participants with Treatment-emergent Adverse Events (TEAEs) by Severity	TEAEs are defined as AEs with onset or worsening on or after date of first dose of study treatment. Severity scale ranges from Grade 1 (Mild) to Grade 5 (Death). Grade 1= Mild, Grade 2= Moderate, Grade 3= Severe, Grade 4= Life-threatening, and Grade 5= Death related to AE.	Up to 4 years
Number of Participants with Serious Adverse Events (SAEs)	SAE is any untoward medical occurrence that results in any of the following outcomes: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly/birth defect; suspected transmission of any infectious agent via a medicinal product or medically important.	Up to 4 years
Number of Participants with Adverse Events of Special Interest (AESIs)	Number of participants with AESI will be reported. Cytokine release syndrome, neurotoxicity, prolonged and recurrent cytopenias, and second primary malignancies will be considered to be AESIs.	Up to 4 years
Number of Participants with Clinically Significant Abnormalities in Safety Laboratory Tests	Number of participants with clinically significant abnormalities in laboratory safety tests (such as serum chemistry, hematology, infectious diseases testing, and urinalysis) will be reported.	Up to 4 years
Number of Participants with Clinically Significant Abnormalities in Vital Signs	Number of participants with clinically significant abnormalities in vital signs (including temperature, pulse/heart rate, respiratory rate, oxygen saturation, and blood pressure) will be reported.	Up to 4 years
Number of Participants with Clinically Significant Abnormalities in Physical Examination	Number of participants with clinically significant abnormalities in physical examination will be reported.	Up to 4 years
Partial Response (PR) Rate	PR rate is defined as percentage of participants who achieve PR according to IMWG response criteria.	Up to 4 years
Very Good Partial Response (VGPR) Rate	VGPR rate is defined as percentage of participants who achieve VGPR according to IMWG response criteria.	Up to 4 years
Complete Response (CR) Rate	CR rate is defined as percentage of participants who achieve CR according to IMWG response criteria.	Up to 4 years
Stringent Complete Response (sCR) Rate	sCR rate is defined as percentage of participants who achieve sCR according to IMWG response criteria.	Up to 4 years
Clinical Benefit Rate (CBR)	CBR (CBR=ORR [sCR+CR+VGPR+PR]+minimal response [MR]) is defined as percentage of participants who achieve CBR according to IMWG response criteria.	Up to 4 years
Duration of Response (DOR)	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 response criteria.	Up to 4 years
Progression Free Survival (PFS)	PFS defined as the time from the date of the initial infusion of cilta-cel out-of-specification (OOS) to the date of first documented disease progression, as defined in the IMWG response criteria, or death due to any cause, whichever occurs first.	Up to 4 years
Overall Survival (OS)	OS is measured from the date of the initial infusion of cilta-cel OOS to the date of the participant's death. If the participant is alive or the vital status is unknown, then the participant's data will be censored at the date the participant was last known to be alive.	Up to 4 years
Minimal Residual Disease (MRD) Negative Rate	MRD negative rate is defined as the percentage of participants in CR with negative MRD status.	Up to 4 years
Number of Participants with Presence of Replication Competent Lentivirus	Number of participants with presence of replication competent lentivirus will be reported.	Up to 4 years

Collaborators and Investigators

• Sponsor: Janssen Scientific Affairs, LLC
• Investigators: Study Director: Janssen Scientific Affairs, LLC Clinical Trial, Janssen Scientific Affairs, LLC

Study record dates

Study Major Dates

• Study Start (Actual): May 13, 2022
• Primary Completion (Actual): November 30, 2023
• Study Completion (Actual): January 16, 2024

Study Registration Dates

• First Submitted: April 21, 2022
• First Submitted That Met QC Criteria: April 21, 2022
• First Posted (Actual): April 26, 2022

Study Record Updates

• Last Update Posted (Estimated): February 5, 2024
• Last Update Submitted That Met QC Criteria: February 2, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Immunoproliferative Disorders; Hematologic Diseases; Hemorrhagic Disorders; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Multiple Myeloma; Neoplasms, Plasma Cell; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Cyclophosphamide; Fludarabine
• Other Study ID Numbers: CR109014; 68284528MMY2005 (Other Identifier: Janssen Scientific Affairs, LLC)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD 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

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No