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 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, 02114
      • Massachusetts General Hospital
    • Boston, Massachusetts, United States, 02215
      • Dana Farber Cancer Institute
  • 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 the percentage of participants who had partial response (PR) or better (sCR+CR+VGPR+PR) according to the International Myeloma Working Group (IMWG) response criteria, as assessed by the investigator. CR: Negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas and less than (<) 5 percentage (%) plasma cells (PCs) in bone marrow; sCR: CR+Normal free light chain ratio and absence of clonal cells in bone marrow by immunohistochemistry or immuno fluorescence; PR: greater than equal to (>=) 50% reduction of serum M-protein and reduction in 24-hour urinary M-protein by >= 90 percentage (%) or to <200 mg/24 hours; VGPR: Serum and urine M-protein detectable by immunofixation but not on electrophoresis or 90% or greater reduction in serum M-protein plus urine M-protein level <100 mg per 24 hour.	From Day 1 (post infusion) up to 18.6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Treatment-emergent Adverse Events (TEAEs)	Number of participants with TEAEs were reported. An AE was any untoward medical occurrence in a participant participating in a clinical study that did not necessarily had a causal relationship with the pharmaceutical/biological agent under study. TEAEs are defined as any AE that occurred on or after the start of cilta-cel OOS infusion through 100 days after the cilta-cel OOS infusion or the start of subsequent anti-myeloma therapy, whichever was earlier; or any AE that was considered related to study intervention regardless of the start date of the event; or any AE that was present at baseline (Day 1, infusion of cilta-cel OOS) but worsens in toxicity grade or is subsequently considered related to study intervention by the investigator.	From Day 1 up to 100 days post cilta-cel OOS infusion (Up to 100 days)
Number of Participants With Treatment-emergent Adverse Events (TEAEs) by Severity	An AE was any untoward medical occurrence in a participant participating in a clinical study that did not necessarily had a causal relationship with the pharmaceutical/biological agent under study. TEAEs were defined as any AE that occurs on or after the start of cilta-cel OOS infusion through 100 days after the cilta-cel OOS infusion or the start of subsequent anti-myeloma therapy, whichever was earlier; or any AE that is considered related to study intervention regardless of the start date of the event; or any AE that was present at baseline (Day 1, pre-infusion of cilta-cel OOS) but worsens in toxicity grade or was subsequently considered related to study intervention by the investigator. Severity was assessed using National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0 as: Grade 1: Mild; Grade 2: Moderate; Grade 3: Severe; Grade 4: Life-threatening; Grade 5: Death related to adverse event.	From Day 1 up to 100 days post cilta-cel OOS infusion (Up to 100 days)
Number of Participants With Treatment-emergent Serious Adverse Events (TESAEs)	Number of participants with serious TESAEs were reported. A SAE was defined as any untoward medical occurrence that results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, leads to a congenital anomaly/birth defect in the offspring of a participant, or was an important medical event. TESAEs were defined as any SAE that occurs on or after the start of cilta-cel OOS infusion through 100 days after the cilta-cel OOS infusion or the start of subsequent anti-myeloma therapy, whichever was earlier; or any SAE that was considered related to study intervention regardless of the start date of the event; or any SAE that was present at baseline but worsens in toxicity grade or was subsequently considered related to study intervention by the investigator.	From Day 1 up to 100 days post cilta-cel OOS infusion (Up to 100 days)
Number of Participants With Treatment-emergent Adverse Event of Special Interest (AESIs): Cytokine Release Syndrome (CRS), Immune Effector Cell-Associated Neurotoxicity (ICANS), Other Neurotoxicities, and Secondary Primary Malignancies	Number of participants with treatment-emergent AESIs: CRS, ICANS, other neurotoxicities, and secondary primary malignancies were reported. AESIs include the anticipated risks of treatment with study drug and events that may be related to multiple sclerosis comorbidities. Treatment-emergent AESIs were defined as any AESI that occurs on or after the start of cilta-cel OOS infusion through 100 days after the cilta-cel OOS infusion or the start of subsequent anti-myeloma therapy, whichever was earlier; or any AESI that was considered related to study intervention regardless of the start date of the event; or any AESI that was present at baseline but worsens in toxicity grade or was subsequently considered related to study intervention by the investigator.	From Day 1 up to 100 days post cilta-cel OOS infusion (Up to 100 days)
Number of Participants With Treatment-emergent Adverse Event of Special Interest (AESIs): Prolonged and Recurrent Cytopenias	Number of participants with treatment-emergent AESIs: prolonged and recurrent cytopenias were reported. AESIs include the anticipated risks of treatment with study drug and events that may be related to multiple sclerosis comorbidities. It included Thrombocytopenia, Neutropenia, Lymphopenia, and Anaemia. Treatment-emergent AESIs were defined as any AESI that occurs on or after the start of cilta-cel OOS infusion through 100 days after the cilta-cel OOS infusion or the start of subsequent anti-myeloma therapy, whichever was earlier; or any AESI that was considered related to study intervention regardless of the start date of the event; or any AESI that was present at baseline but worsens in toxicity grade or was subsequently considered related to study intervention by the investigator. Severity was assessed using NCI-CTCAE version 5.0 as: Grade 1: Mild; Grade 2: Moderate; Grade 3: Severe; Grade 4: Life-threatening; Grade 5: Death related to adverse event.	From Day 1 up to 100 days post cilta-cel OOS infusion (Up to 100 days)
Number of Participants by Worst Grade Abnormalities in Clinical Laboratory Tests: Hematology (Including Coagulation) and Chemistry After Cilta-cel OOS Infusion	Number of participants by worst grade abnormalities in clinical laboratory tests: hematology (including coagulation) and chemistry, after cilta-cel OOS infusion were reported. Grades were assessed using NCI-CTCAE (version 5.0), as: Grade 1: Mild; Grade 2: Moderate; Grade 3: Severe; Grade 4: Life-threatening. Participants with normal values or a value in the opposite direction (for laboratory tests with bidirectional toxicities defined) were assigned Grade 0. Only those categories in which at least 1 participant had data were reported.	From Day 1 (post infusion) up to 18.6 months
Partial Response (PR) Rate	PR rate was defined as percentage of participants who achieved PR according to IMWG response criteria. PR was defined as per IMWG criteria as >= 50% reduction of serum M-protein and reduction in 24 hours urinary M-protein by >= 90% or to < 200 mg/24hours. If the serum and urine M-protein were unmeasurable, a >= 50% decrease in the difference between involved and uninvolved Free light chain (FLC) levels was required in the place of the M-protein criteria. If serum and urine M-protein were not measurable, and serum free light assay was also not measurable, >=50% reduction in bone marrow plasma cells is required in place of M-protein, provided baseline bone marrow plasma cells percentage was >=30%. In addition to the above listed criteria, if present at baseline, a >= 50% reduction in the size of soft tissue plasmacytomas was also required.	From Day 1 (post infusion) up to 18.6 months
Very Good Partial Response (VGPR) Rate	VGPR rate is defined as percentage of participants who achieved best response of VGPR according to IMWG response criteria. As per IMWG response criteria, VPGR: serum and urine M-component detectable by immunofixation but not on electrophoresis, or >=90% reduction in serum M-component plus urine M-component <100 mg/24 hours.	From Day 1 (post infusion) up to 18.6 months
Complete Response (CR) Rate	CR rate is defined as percentage of participants who achieved best response of CR according to IMWG response criteria. CR is defined as per IMWG criteria as negative immunofixation of serum and urine, and disappearance of any soft tissue plasmacytomas, and <5% PCs in bone marrow. No evidence of initial monoclonal protein isotype(s) on immunofixation of the serum and urine.	From Day 1 (post infusion) up to 18.6 months
Clinical Benefit Rate (CBR)	Clinical benefit rate was defined as the percentage of participants who achieved a minimal response (MR) or better (including MR, PR, VGPR, CR, and sCR). MR was defined as per IMWG criteria as >=25% but less than or equal to (<=) 49% reduction of serum M-protein and reduction in 24-hour urine M-protein by 50% to 89%. In addition to the above criteria, if present at baseline, >=50% reduction in the size of soft tissue plasmacytomas was also required.	From Day 1 (post infusion) up to 18.6 months
Stringent Complete Response (sCR) Rate	sCR rate is defined as percentage of participants who achieved sCR according to IMWG response criteria. sCR is defined per IMWG criteria as CR plus normal FLC ratio, and absence of clonal PCs by immunohistochemistry or 2- to 4-color flow cytometry. CR is defined as per IMWG as negative immunofixation of serum and urine, and disappearance of any soft tissue plasmacytomas, and <5% PCs in bone marrow. No evidence of initial monoclonal protein isotype(s) on immunofixation of the serum and urine.	From Day 1 (post infusion) up to 18.6 months
Duration of Response (DOR)	DOR calculated in responders (with PR or better response) from date of initial documentation of response (PR or better) to date of first documented evidence of progressive disease (PD) as per IMWG criteria, or death due to any cause, whichever occurs first. PD: increase of 25% from lowest response value: serum and urine M-component (absolute increase must be >=0.5 grams/deciliter [g/dL] and >=200 mg/24 hours, respectively); only in participants without measurable serum and urine M-protein levels, difference between involved and uninvolved FLC levels (absolute increase must be >10 mg/dL); only in participants without measurable serum and/or urine M-protein levels and without measurable disease by FLC levels, bone marrow PC % (absolute increase must be >=10%), appearance of new lesion; definite development of new bone lesions or definite increase in the size of existing bone lesions, >=50% increase in circulating PCs (minimum of 200 cells per uL) if this was the only measure of disease.	From Day 1 (post infusion) up to 18.6 months
Progression Free Survival (PFS)	PFS defined as the time from the date of the initial infusion of cilta-cel OOS to the date of first documented disease progression as per IMWG criteria, or death due to any cause, whichever occurs first. PD: increase of 25% from lowest response value: serum and urine M-component (absolute increase must be >=0.5 g/dL and >=200 mg/24 hours, respectively); only in participants without measurable serum and/or urine M-protein levels the difference between involved and uninvolved FLC levels (absolute increase must be >10 mg/dL); only in participants without measurable serum and urine M-protein levels and without measurable disease by FLC levels, bone marrow PC percentage (absolute increase must be >=10%), appearance of a new lesion; definite development of new bone lesions or definite increase in the size of existing bone lesions, >=50% increase in circulating PCs (minimum of 200 cells per uL) if this was the only measure of disease.	From Day 1 (post infusion) up to 18.6 months
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 was censored at the date the participant was last known to be alive.	From Day 1 (post infusion) up to 18.6 months
Minimal Residual Disease (MRD)-Negative Rate	MRD-negative rate is defined as the percentage of participants with negative MRD status (at 10^-4, 10^-5 and 10^-6 cutoffs) by bone marrow aspirate.	From Day 1 (post infusion) up to 18.6 months
Number of Participants With Presence of Replication Competent Lentivirus	Number of participants with presence of replication competent lentivirus (with evaluable sample) were reported.	Predose, 3, 6, 12 months after cilta-cel infusion on Day 1

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): December 15, 2023

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 (Actual): April 25, 2025
• Last Update Submitted That Met QC Criteria: April 24, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

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