Study of Out of Specification for Tisagenlecleucel

Novartis

Status and phase: Enrolling; Phase 3

Conditions: Diffuse Large B-cell Lymphoma; B-cell Acute Lymphoblastic Leukemia

Treatments: Biological: CTL019

Study type: Interventional

Funder types: Industry

Identifiers

NCT04094311

CCTL019B2302

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 200 estimated patients

Sex: All

Ages: Under 100 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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.

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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200 participants in 3 patient groups

Group A: pALL

Experimental group

Description:

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.

Treatment:

Biological: CTL019

Group B: r/r LBCL

Experimental group

Description:

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.

Treatment:

Biological: CTL019

Group C: r/r NHL

Experimental group

Description:

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.

Treatment:

Biological: CTL019