Study of Out of Specification for Tisagenlecleucel

Study Overview
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Brief Summary
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This study will evaluate the safety of tisagenlecleucel that is out of specification( OOS) for release as commercial product. Specifically, this study will evaluate the safety of CTL019 in the patients treated within the approved label by Japan Health Authority in Part 2. Only for Part 1, in addition to safety, key efficacy of CTL019 will also be evaluated.

Detailed Description
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This is a single-arm, open-label, multicenter, interventional Phase IIIb study in pediatric/young adult patients with relapsed/refractory (r/r) B-cell acute lymphoblastic leukemia (pALL) and adult patients with r/r large B-cell lymphoma (LBCL) including diffuse large B-cell lymphoma (DLBCL) not otherwise specified, high-grade B cell lymphoma, and DLBCL arising from follicular lymphoma for Part 1 and and r/r ALL and r/r non-Hodgkin's lymphomas (NHL) for Part 2 Patients whose final manufactured tisagenlecleucel patient-specific batch does not meet the approved local commercial release specifications are eligible for inclusion. Each case will be individually assessed and approved by the Novartis manufacturing facility and the Novartis global medical team (including Patient Safety). Following a single infusion of CTL019, the patient will be followed for 3 months for Part 1, and 1 day for Part 2.

Official Title
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A Phase IIIb Study of the Safety and Efficacy of Tisagenlecleucel Out of Specification for Commercial Release in Patients Who Are Consistent With the Label Indication

Conditions
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B-cell Acute Lymphoblastic Leukemia, Diffuse Large B-cell Lymphoma

Intervention / Treatment
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* Biological: CTL019


Participation Criteria
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Eligibility Criteria
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Key inclusion criteria: Signed informed consent/assent must be obtained for this study prior to participation in the study. Patients for whom the final manufactured tisagenlecleucel product does not meet the commercial release specifications. Not excluded from commercial manufacturing under the Health Authority-approved tisagenlecleucel prescribing information for their respective country/region. OOS material has not been deemed to pose an undue safety risk to the patient. Patient is suffering from a serious or life-threatening disease or condition. Repeat leukapheresis is not clinically appropriate per the investigator assessment. Key exclusion criteria: For part 1, patients meeting any of the following criteria are not eligible for inclusion in this study: Human immunodeficience virus (HIV) positive patients. Patients with active replication of Hepatitis B virus (HBV) or Hepatitis C virus (HCV). Patients with primary central nervous system (CNS) lymphoma. History of hypersensitivity to any drugs or metabolites of similar chemical classes as tisagenlecleucel. Uncontrolled active infection or inflammation. Any medical condition identified by the investigator that may impact the assessment of the safety or efficacy outcomes in relation to study treatment. Pregnant or nursing (lactating) women. For part 2, exclusion criteria are not set; however, administration should be performed in accordance with the latest versions of the package insert of CTL019.
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group A: pALL<br>Pediatric/young adult patients with r/r pALL who meet the indication in the Health Authority-approved CTL019 package insert in the respective country/region whose final manufactured product is OOS for commercial release, but it is considered that the benefit-risk profile may remain favorable and the usual expected benefits of infusing such a product outweigh the potential risks for the patient. | Biological: CTL019<br>* A single intravenous (i.v.) infusion of CAR-positive viable T cells.<br>* Other names: Tisagenlecleucel;|
| Experimental: Group B: r/r LBCL<br>Adult patients with r/r LBCL including DLBCL not otherwise specified, high grade B-cell lymphoma, and DLBCL arising from follicular lymphoma, that is consistent with the Health Authority-approved indication in the package insert for CTL019 in the respective country/region whose final manufactured product is OOS for commercial release, but it is considered that the benefit-risk profile may remain favorable and the usual expected benefits of infusing such a product outweigh the potential risks for the patient. | Biological: CTL019<br>* A single intravenous (i.v.) infusion of CAR-positive viable T cells.<br>* Other names: Tisagenlecleucel;|
| Experimental: Group C: r/r NHL<br>Adult patients with r/r NHL in consistent with the Health Authority approved indication in the package insert for CTL019 in Japan whose final manufactured product is OOS for commercial release, but it is considered that the benefit-risk profile may remain favorable and the usual expected benefits of infusing such a product outweigh the potential risks for the patient. | Biological: CTL019<br>* A single intravenous (i.v.) infusion of CAR-positive viable T cells.<br>* Other names: Tisagenlecleucel;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of participants with Adverse Events (AEs) | Percentage of participants with Serious AEs (SAEs) and non-SAEs | From Screening up to 3 months for Part 1 and 1 day for Part 2 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part 1: Overall Remission Rate in Group A (pALL) | Overall Remission Rate is defined as the percentage of participants wiho achieve a complete remission (CR) and CR with incomplete blood count recovery (CRi) within 3 months following infusion of CTL019 as determined by the local investigator assessment for participants in group A (part 1). | Up to 3 months | 
| Part 1: Overall Response Rate in Group B (LBCL) | ORR is defined as the percentage of patients who achieve a domplete response and partial response within 3 months following infusion of CTL019 as determined by the local investigator assessment for participants in group B (part 1). | Up to 3 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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out of specification, tisagenlecleucel, acute lymphoblastic leukemia, large B-cell lymphoma, relapsed/refractory, pediatric, young adult patients