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

JRCT ID: jRCT2053220159

Registered date:30/01/2023

Basic Information

• Recruitment status: Pending
• Health condition(s) or Problem(s) studied: Multiple Myeloma
• Date of first enrollment: 23/07/2023
• Target sample size: 330
• Countries of recruitment: United States Of America,Japan
• Study type: Interventional

Intervention(s)

Cilta-cel : Cilta-cel will be administered as an IV infusion : 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).

Lymphodepleting Therapy (Cyclophosphamide and Fludarabine) : Lymphodepleting therapy (cyclophosphamide and fludarabine) will be administered intravenously.

Outcome(s)

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

Secondary Outcome

Number of Participants with Treatment-emergent Adverse Events (TEAEs) : Up to 4 years : Treatment-emergent adverse events (TEAEs) are defined as AEs with onset or worsening on or after date of first dose of study treatment.

Number of Participants with Treatment-emergent Adverse Events (TEAEs) by Severity : Up to 4 years : 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.

Number of Participants with Serious Adverse Events (SAEs) : Up to 4 years : 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.

Number of Participants with Adverse Events of Special Interest (AESIs) : Up to 4 years : 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.

Number of Participants with Clinically Significant Abnormalities in Safety Laboratory Tests : Up to 4 years : Number of participants with clinically significant abnormalities in laboratory safety tests (such as serum chemistry, hematology, infectious diseases testing, and urinalysis) will be reported.

Number of Participants with Clinically Significant Abnormalities in Vital Signs : Up to 4 years : 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.

Number of Participants with Clinically Significant Abnormalities in Physical Examination : Up to 4 years :
Number of participants with clinically significant abnormalities in physical examination will be reported.

Partial Response (PR) Rate : Up to 4 years : PR rate is defined as percentage of participants who achieve PR according to IMWG response criteria.

Very Good Partial Response (VGPR) Rate : Up to 4 years : VGPR rate is defined as percentage of participants who achieve VGPR according to IMWG response criteria.

Complete Response (CR) Rate : Up to 4 years : CR rate is defined as percentage of participants who achieve CR according to IMWG response criteria.

Stringent Complete Response (sCR) Rate : Up to 4 years : sCR rate is defined as percentage of participants who achieve sCR according to IMWG response criteria.

Clinical Benefit Rate (CBR) : Up to 4 years : CBR (CBR=ORR[sCR+CR+VGPR+PR]+minimal response [MR]) is defined as percentage of participants who achieve CBR according to IMWG response criteria.

Duration of Response (DOR) : Up to 4 years : 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.

Progression Free Survival (PFS) : Up to 4 years : 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.

Overall Survival (OS) : Up to 4 years : 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.

Minimal Residual Disease (MRD) Negative Rate : Up to 4 years : MRD negative rate is defined as the percentage of participants in CR with negative MRD status.

Number of Participants with Presence of Replication Competent Lentivirus : Up to 4 years : Number of participants with presence of replication competent lentivirus will be reported.

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: Not applicable
• Gender: Both

Include 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

Exclude 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

Related Information

• Primary Sponsor: Fujikawa Ei
• Secondary ID(s): NCT05347485