Expanded Access Protocol (EAP) for Subjects Receiving Lisocabtagene Maraleucel that is Nonconforming for Commercial Release

JRCT ID: jRCT2053200162

Registered date:26/03/2021

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: Relapsed and/or refractory large B-cell lymphoma
• Date of first enrollment: 13/12/2021
• Target sample size: 30
• Countries of recruitment: United States of America,Japan,Canada,Japan
• Study type: Interventional

Intervention(s)

Leukapheresis is performed at a medical institution to collect enough peripheral blood mononuclear cells (PBMCs) for producing JCAR017 cell products, and the cells are transported to the factory after collection. CD4-positive cells and CD8-positive cells are isolated from PBMCs, respectively. Anticancer therapy is allowed for disease control during the manufacture of JCAR017 (ie, between the completion of leukapheresis and the start of lymphodepleting chemotherapy) if necessary.
Fludarabine (30mg/m^2/day) and cyclophosphamide (300mg/m^2/day) are administered intravenously for 3 days as lymphodepleting chemotherapy. 2-7 days after the end of lymphodepleting chemotherapy, JCAR017 was added to CAR T cells 1*10^8
Administer intravenously at a dose of (5*10^7 CD8-positive CAR T cells and 5*10^7 CD4-positive CAR T cells). However, the number of cells may be small in the JCAR017-EAP-001 trial.

Outcome(s)

• Primary Outcome: [Safety] Type, frequency, and severity of selected adverse events (AEs) and laboratory abnormalities; Up to 3 months post date of infusion of nonconforming lisocabtagene maraleucel

Secondary Outcome

[Efficacy, Overall Response Rate (ORR)]Defined as the percentage of subjects with a best overall response (BOR) of either complete response (CR) or partial response (PR) following nonconforming lisocabtagene maraleucel infusion until disease progression, end of study, the start of another anticancer therapy or hematopoietic stem cell transplantation (HSCT) using "The Lugano Classification". ; Up to 3 months post date of infusion of nonconforming lisocabtagene maraleucel
[Efficacy, Complete Response (CR) Rate]Defined as the percentage of subjects achieving a BOR of CR following nonconforming lisocabtagene maraleucel infusion until disease progression, end of study, the start of another anticancer therapy or HSCT using "The Lugano Classification". ; Up to 3 months post date of infusion of nonconforming lisocabtagene maraleucel

Key inclusion & exclusion criteria

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

Include criteria

1. Subject and/or LAR must understand and voluntarily sign an ICF prior to any studyrelated assessments/procedures being conducted.
2. Subject has relapsed and/or refractory large B-cell lymphoma and is, per the treating physician assessment, eligible for treatment with lisocabtagene maraleucel per the approved prescribing information.
3. Subject is >= 18 years of age at the time of signing the ICF.
4. Subject had a subject-specific batch of lisocabtagene maraleucel manufactured intended for commercial treatment; however, the final manufactured product did not meet commercial release criteria. The Sponsor Internal Review Process has determined that the nonconforming lisocabtagene maraleucel may be released for use under the EAP.
5. Remanufacturing (eg, repeat leukapheresis and manufacturing) is deemed not feasible or clinically inappropriate per assessment of the treating physician in discussion with the subject. The reason for not choosing to remanufacture or to undergo a second leukapheresis must be documented in source documentation and captured on the CRF.
6. Subject is clinically stable, has recovered from any prior toxicities prior to receiving LD chemotherapy, and has adequate bone marrow function to receive LD chemotherapy. The treating physician is advised to contact the Medical Monitor in the event there is any concern regarding administration of LD chemotherapy.
7. Females of childbearing potential (FCBP) must:
a. Have a negative pregnancy test as verified by the treating physician within 7 days prior to the first dose of lymphodepleting (LD) chemotherapy following institutional testing methodology practices. This applies even if the subject practices true abstinence from heterosexual contact.
b. Either commit to true abstinence from heterosexual contact or agree to use, and be able to comply with, effective contraception without interruption. Contraception methods must include 1 highly effective method from screening until at least 12 months after the nonconforming lisocabtagene maraleucel administration.
c. Agree to abstain from breastfeeding during study participation and for at least 12 months following nonconforming lisocabtagene maraleucel administration.
d. There are insufficient exposure data to provide any recommendation concerning the duration of contraception and the abstaining from breastfeeding following treatment with lisocabtagene maraleucel. Any decision regarding contraception and breastfeeding after infusion should be discussed with the treating physician.
8. Male subjects must:
a. Practice true abstinence or agree to use a condom during sexual contact with a pregnant female or a female of childbearing potential for at least 12 months after nonconforming lisocabtagene maraleucel administration even if the subject has undergone a successful vasectomy.
b. There are insufficient exposure data to provide any recommendation concerning the duration of contraception following treatment with lisocabtagene maraleucel. Any decision regarding contraception after infusion should be discussed with the treating physician.
9. Subject must agree to not donate blood, organs, tissue, sperm or semen and egg cells for usage in other individuals for at least 1 year following nonconforming lisocabtagene maraleucel administration. There are insufficient exposure data to provide any recommendation concerning the duration of refraining from tissue donation following treatment with lisocabtagene maraleucel. Therefore, subjects treated with lisocabtagene maraleucel should not donate blood, organs, tissues, and cells for transplantation.

Exclude criteria

1. Subject has a hypersensitivity to the active substance or to any of the excipients.
2. Subject should not experience a significant worsening in clinical status that would, in the opinion of the treating physician, either increase the risk of AEs associated with LD chemotherapy, or exclude them from treatment with nonconforming lisocabtagene maraleucel.
3. Subject has any significant medical condition, laboratory abnormality, or psychiatric illness, sociologic or geographic condition that would prevent the subject from participating in the EAP, complying with protocol requirements in the Investigator's judgement.
4. Subject has any condition and/or laboratory abnormality that places the subject at unacceptable risk if he/she were to participate in the EAP based on the Investigator's judgement.
5. Pregnant or nursing women or has intention of becoming pregnant during the study.
6. Subjects with central nervous system (CNS)-only involvement by malignancy (note: subjects with secondary CNS involvement are allowed on study)
7. Subject has active hepatitis B, hepatitis C, or human immunodeficiency virus (HIV) infection at the time of pretreatment evaluation.
8. Subject has uncontrolled systemic fungal, bacterial, viral or other infection despite appropriate antibiotics or other treatment at the time of nonconforming lisocabtagene maraleucel administration.
9. Subject has presence of acute or chronic graft-versus-host disease (ie, GVHD).
10. Use of the following:
a. Therapeutic doses of corticosteroids (defined as > 20 mg/day prednisone or equivalent) within 72 hours prior to nonconforming lisocabtagene maraleucel administration. Physiologic replacement, topical, and inhaled steroids are permitted.
b. Low dose chemotherapy (eg, vincristine, rituximab, cyclophosphamide =< 300 mg/m^2) given after leukapheresis to maintain disease control must be stopped >= 7 days prior to LD chemotherapy.
c. Cytotoxic chemotherapeutic agents that are not considered lymphotoxic within 1 week of LD chemotherapy. Oral chemotherapeutic agents, including
lenalidomide and ibrutinib, are allowed if at least 3 half-lives have elapsed prior to LD chemotherapy.
d. Donor lymphocyte infusions within 6 weeks of nonconforming lisocabtagene maraleucel administration

Related Information

• Primary Sponsor: Okazuka Kiyoshi
• Secondary ID(s): NCT04400591