Study of Efficacy and Safety of Reinfusion of Tisagenlecleucel in Pediatric and Young Adult Patients With Acute Lymphoblastic Leukemia (ALL)

Phase 2

Terminated

• Conditions: Acute Lymphoblastic Leukemia
• Interventions: Biological: Tisagenlecleucel

• Registration Number: NCT04225676
• Lead Sponsor: Novartis Pharmaceuticals

Brief Summary

This was a multi-center Phase II study investigating the efficacy and safety of reinfusion of tisagenlecleucel in pediatric and young adult patients with acute lymphoblastic leukemia (ALL) who were treated with tisagenlecleucel and experience B cell recovery.

Detailed Description

This trial was a phase II, open label, multi-center trial to determine the efficacy and safety of tisagenlecleucel re-infusion in pediatric and adolescent young adult (AYA) patients with acute lymphoblastic leukemia (ALL) experiencing loss of B cell aplasia. Loss of B-cell aplasia is defined as: peripheral blood (PB) absolute B lymphocyte count ≥ 50/µL, OR PB B lymphocyte ≥ 10% of the total lymphocytes. B-cell aplasia is defined as PB absolute B lymphocyte count \<50/µL.

The study had the following phases for all patients: Screening, Treatment and Follow-up. The total duration of the study was about 12 months. After tisagenlecleucel re-infusion, efficacy was assessed at months 1, 3, 6, and End of Study at which time blood samples were obtained.

The study stopped early due to slow enrollment into the trial. The rate of enrollment made the trial no longer feasible to continue.

The patients were able to voluntarily withdraw from the study for any reason, at any time. Patients who received commercial tisagenlecleucel had to be followed for up to 15 years post-infusion. Patients could have been followed under the Center for International Blood and Marrow Transplant Research (CIBMTR) cellular therapy registry if consented for participation. For patients who do not provide consent for participation in the Center for International Blood and Marrow Transplant Research (CIBMTR) registry, adverse events were to be reported for 15 years or until the patient enrolls in the registry.

Study Timeline

• Study First Submitted: 2020-01-09
• Study First Submitted QC: 2020-01-09
• Study First Posted: 2020-01-13
• Study Start: 2020-10-19
• Primary Completion: 2021-10-19
• Study Completion: 2021-10-19
• Results First Submitted: 2022-04-14
• Results First Submitted QC: 2022-07-08
• Results First Posted: 2022-07-15
• Status Verified: 2023-01
• Last Update Submitted: 2023-01-27
• Last Update Posted: 2023-01-30

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 5

Inclusion Criteria

• Signed informed consent must be obtained prior to participation in the study
• Must have an additional dose of unexpired, commercial tisagenlecleucel available and prescribed by a physician in the course of medical practice
• Age up to and including 25 years
• Patients must have CD-19+ Leukemia
• Patients who were previously treated with tisagenlecleucel and present with evidence of B-cell recovery as defined by: Peripheral blood (PB) absolute B lymphocyte count ≥ 50/µL, OR PB B lymphocyte ≥ 10% of the total lymphocytes

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Exclusion Criteria

• Prior gene therapy other than tisagenlecleucel
• Prior adoptive T cell therapy other than tisagenlecleucel
• Active CNS involvement by malignancy
• Active or latent hepatitis B or active hepatitis C, or any uncontrolled infection at screening
• HIV positive test within 8 weeks of screening

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Tisagenlecleucel	Tisagenlecleucel	Tisagenlecleucel Cell Dispersion for Infusion given once during the study. The approved dose range for tisagenlecleucel is: 0.2 to 5.0×106 CAR positive viable T cells / kg for patients' ≤ 50 kg body weight or 0.1 to 2.5×108 CAR-positive viable T cells for patients \> 50 kg body weight.

Primary Outcome Measures

Name	Time	Method
Percentage of Patients Who Establish B Cell Aplasia Within 9 Months of Reinfusion	Post-reinfusion up to 9 months (Day 1 is excluded)	Percentage of patients who establish B-cell aplasia at any visit following re-infusion with tisagenlecleucel. B-cell aplasia is defined as peripheral blood (PB) absolute B lymphocyte count \<50/μL. Planned timeframe was 12 months but actual timeframe was approximately 9 months due to early termination of the trial. Day 1 is post lymphodepleting chemotherapy and pre-reinfusion of tisagenlecleucel.

Secondary Outcome Measures

Name	Time	Method
Overall Survival (OS)	Reinfusion up to 9 months	Deaths due to any reason.
Complete Response (CR) or Complete Response With Incomplete Blood Count Recovery (CRi) by Day	Post-reinfusion up to 9 months	Overall remission rate (ORR) was defined as the percentage of participants with a best overall disease response of complete remission (CR) or CR with incomplete blood count recovery (CRi). However, the rate was not calculated due to low enrollment. Participants' best responses have been listed by day and participants may be counted more than once.
Participants With an Event	Reinfusion up to 9 months	An event was defined as one of the following: death from any cause after remission, relapse, treatment failure (defined as no response in the study or discontinuation from the study for death, adverse event, lack of efficacy or progressive disease or new cancer therapy).

Trial Locations

Locations (4)

Childrens Hospital Los Angeles Divisionof Hematology/Oncology; 🇺🇸 Los Angeles, California, United States

Ann and Robert H Lurie Childrens Hospital of Chicago; 🇺🇸 Chicago, Illinois, United States

UT Southwestern Medical Center; 🇺🇸 Dallas, Texas, United States

Children s Mercy Hospital; 🇺🇸 Kansas City, Missouri, United States