Expanded Access Protocol (EAP) for Subjects Receiving Lisocabtagene Maraleucel

JCAR017-EAP-001 is an expanded access protocol (EAP) designed to evaluate the safety and efficacy of non-conforming for commercial release lisocabtagene maraleucel in subjects with relapsed and/or refractory large B-cell lymphoma (LBCL).

The study will enroll male and female subjects over 18 years of age who have previously agreed to receive the approved drug, lisocabgagene maraleucel, as routine care for treatment of their disease. As part of their routine care, the subjects’ T-cells were modified in order to manufacture the lisocabtagene maraleucel T-cells as a commercial product for their disease treatment. The lisocabtagene maraleucel T-cells that were produced (and will be used for this study) do not meet all of the pre-specified release criteria to be used as a routine prescription drug. Subjects will receive lymphodepleting (LD) chemotherapy 2-7 days before administration of the study drug.

The study has three treatment periods including the following: 

1. Pre-treatment will consist of clinical evaluation that occurred prior to manufacturing of study drug and pre-treatment evaluation.
2. Treatment will start with the administration of the 1st dose of lymphodepletion (LD) chemotherapy and continues through Day 1 of non-conforming lisocabtagene maraleucel administration. Subjects will receive IV administration of fludarabine and cyclophosphamide for LD chemotherapy.
3. Post-treatment will include follow-up assessments for safety and disease status for up to 3 months following administration of the study drug.

Subjects will remain on the study for up to three months following date of administration of the non-conforming lisocabtagene maraleucel infusion. Subjects will be asked to participate in a separate 15-year long-term follow-up registry study.

The EAP may continue as long as lisocabtagene maraleucel remains a commercially-available product and the EAP is required for administration of non-conforming lisocabtagene maraleucel. The study may enroll subjects as long as the EAP remains open. A specified number of subjects is not pre-defined.

In order to participate you must meet the following criteria:

• Subject and/or LAR must understand and voluntarily sign an ICF prior to any study related assessments/procedures being conducted.
• 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.
• Subject is > 18 years of age at the time of signing the ICF.
• 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 non-conforming lisocabtagene maraleucel may be released for use under the EAP.
• 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.
• 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.
• Females of childbearing potential (FCBP*) must:
  • 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.
  • 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 non-conforming lisocabtagene maraleucel administration.
  • Agree to abstain from breastfeeding during study participation and for at least 12 months following non-conforming lisocabtagene maraleucel administration.
  • 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.
    • * Note: A female subject of childbearing potential (FCBP) is a female who: 1) has achieved menarche at some point, 2) has not undergone a hysterectomy or bilateral oophorectomy or 3) has not been naturally postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 24 consecutive months (ie, has had menses at any time in the preceding 24 consecutive months).
    • ** Note: True abstinence is acceptable when this is in line with the preferred and usual lifestyle of the subject. In contrast, periodic abstinence (eg, calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception.
    • ***Note: Highly effective methods are defined as those that result in a low failure rate (ie, less than 1% per year) when used consistently and correctly. The following are examples of highly effective methods of contraception: Intrauterine device (IUD), Hormonal (birth control pill, injections, implants), Tubal ligation, Partner's vasectomy.
• Male subjects must:
  • Practice true abstinene 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 non-conforming lisocabtagene maraleucel administration even if the subject has undergone a successful vasectomy.
    • ** Note: True abstinence is acceptable when this is in line with the preferred and usual lifestyle of the subject. In contrast, periodic abstinence (eg, calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception.
  • 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.
  • 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 non-conforming 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.

You will be excluded from the study if any of the following criteria apply to you:

• Subject has a hypersensitivity to the active substance or to any of the excipients.
• 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 non-conforming lisocabtagene maraleucel.
• 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 judgment.
• 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 judgment.
• Pregnant or nursing women or has intention of becoming pregnant during the study.
• Subjects with central nervous system (CNS)-only involvement by malignancy (note: subjects with secondary CNS involvement are allowed on study).
• Subject has active hepatitis B, hepatitis C, or human immunodeficiency virus (HIV) infection at the time of pretreatment evaluation.
• Subject has uncontrolled systemic fungal, bacterial, viral or other infection despite appropriate antibiotics or other treatment at the time of non-conforming lisocabtagene maraleucel administration.
• Subject has presence of acute or chronic graft-versus-host disease (ie, GVHD).
• Use of the following:
  • Therapeutic doses of corticosteroids (defined as > 20 mg/day prednisone or equivalent) within 72 hours prior to non-conforming lisocabtagene maraleucel administration. Physiologic replacement, topical, and inhaled steroids are permitted.
  • Low dose chemotherapy (eg, vincristine, rituximab, cyclophosphamide < 300 mg/m2) given after leukapheresis to maintain disease control must be stopped > 7 days prior to LD chemotherapy.
  • Cytotoxic chemotherapeutic agents that are not considered lymphotoxic (see below) 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.
  • Donor lymphocyte infusions within 6 weeks of non-conforming lisocabtagene maraleucel administration

This is a partial list of eligibility requirements. To inquire about your eligibility, please call the contact number provided. If you wish to inquire via email, please include the title of the study in your message.