IRB Study Number 19-796
Status Recruiting
Location Cleveland Clinic Main Campus
Institute Taussig Cancer Institute
Description
To allow treatment with tisagenlecleucel (CTL019) for eligible patients diagnosed with B-cell acute lymphoblastic leukemia (ALL) or large B-cell lymphomas who meet all of the following criteria:
- consistent with the approved prescribing information,
- unable to receive commercially manufactured product due to failure of the incoming apheresis material to meet acceptance specifications or final outgoing product to meet the commercial release specifications or other specification within the prescribing information, and
- where no overwhelming safety concerns has been identified for manufacture and release of the out of specification product. The requesting treating physician submitted a request to Novartis to access tisagenlecleucel that does not meet commercial specifications, which was reviewed and approved by the medical team experienced with tisagenlecleucel and the indication.
Inclusion Criteria
- Written informed consent must be obtained prior to treatment.
- Patient with B-cell acute lymphoblastic leukemia (ALL) or large B-cell lymphoma who were, per the treating physician assessment, eligible for treatment with tisagenlecleucel per the approved prescribing information (PI).
- As per US PI, the approved indications are:
- Patients up to 25 years of age with B-cell precursor acute lymphoblastic leukemia (ALL) that is refractory or in second or later relapse.
- Adult patients with relapsed or refractory (r/r) large B-cell lymphoma after two or more lines of systemic therapy including diffuse large B-cell lymphoma (DLBCL) not otherwise specified, high grade B-cell lymphoma and DLBCL arising from follicular lymphoma.
- For other countries, please follow the locally approved PI or Summary of Product Characteristics (SmPC).
- Has a patient specific batch of tisagenlecleucel allocated, however, either the incoming apheresis material is out of specification due to failure to meet acceptance specifications or the final manufactured product is out of specification due to failure to meet the commercial release specifications or other specification within the prescribing information. Attributes that may be out of specification:
- Incoming leukapheresis: such as leukapheresis shelf life, T-cell percentage, absolute total nucleated cells, absolute T-cell count, and patient's viral testing including hepatitis B, hepatitis C, and HIV.
- Final product: such as appearance (color), CAR identity, purity (T-cell percentage, cell viability, transduction efficiency by CAR quantitative PCR), impurities (residual beads, percentage of viable B-cells), quantity (for dose refer to Section 4), potency (CAR expression by flow cytometry and release of IFN? in response to CD19-expressing target cells), Safety: bacterial endotoxins, sterility, mycoplasma, VSV-G DNA)
- Out of specification material has not been deemed to pose an undue safety risk to the patient
- Is suffering from a serious or life-threatening disease or condition
- Repeat leukapheresis is not clinically appropriate per the treating physician assessment
- Does not have access to a comparable or satisfactory alternative treatment (i.e., comparable or satisfactory treatment is not available or does not exist)
- Is not eligible for participation in any of the IMP's ongoing clinical trials or has recently completed a clinical trial that has been terminated and, after considering other options (e.g., trial extensions, amendments, etc.), the clinical team has determined that treatment is necessary and there are no other feasible alternatives for the patient
- Meets any other relevant medical criteria for compassionate use of the investigational product
- Is not being transferred from an ongoing clinical trial for which they are still eligible
Exclusion Criteria
- Product can be commercially manufactured per the specification of the country in which treatment will occur.
- Evidence of CD19 negative disease in patients with B-cell ALL.
- Active Hepatitis B, active or latent Hepatitis C, and HIV positivity
- Hypersensitivity to the active substance or to any of the excipients. Contraindications of the lymphodepleting chemotherapy must be considered.
- Uncontrolled active infection or inflammation.
- History of unstable angina or myocardial infarction within 6 months prior to screening.
- Any medical condition identified by the investigator that may impact the assessment of the safety or efficacy outcomes in relation to tisagenlecleucel treatment.
- Pregnant or nursing (lactating) women NOTE: Pregnancy status of sexually-active females with reproductive potential should be verified with a pregnancy test before lymphodepletion and prior to tisagenlecleucel infusion.
- Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they agree to use highly effective methods of contraception. Highly effective contraception methods include:
- Total abstinence (when this is in line with the preferred and usual lifestyle of the subject. Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception
- Female sterilization (have had surgical bilateral oophorectomy with or without hysterectomy), total hysterectomy, or tubal ligation at least six weeks before taking study treatment. In case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment
- Male sterilization (at least 6 months prior to screening). For female subjects on the study, the vasectomized male partner should be the sole partner for that subject
- Use of oral, (estrogen and progesterone), injected or implanted hormonal methods of contraception or placement of an intrauterine device (IUD) or intrauterine system (IUS), or other forms of hormonal contraception that have comparable efficacy (failure rate <1%), for example hormone vaginal ring or transdermal hormone contraception. In case of use of oral contraception women should have been stable on the same pill for a minimum of 3 months before enrollment into this study. Women are considered post-menopausal and not of child bearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g. age appropriate history of vasomotor symptoms) or have had surgical bilateral oophorectomy (with or without hysterectomy), total hysterectomy or tubal ligation at least six weeks ago. In the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment is she considered not of child bearing potential. There are insufficient exposure data to provide a recommendation concerning duration of contraception following treatment with tisagenlecleucel.
- Sexually active males must use a condom during intercourse to prevent them from fathering a child AND to prevent delivery of study treatment via seminal fluid to their partner. In addition, male participants must not donate sperm. There are insufficient exposure data to provide a recommendation concerning duration ofEx contraception following treatment with tisagenlecleucel.
