A Second Infusion (Early Reinfusion) of Tisagenlecleucel in Children and Young Adults With B-Cell Acute Lymphoblastic Leukemia(B-ALL)

NCT05460533 | Active Not Recruiting Phase 2 FDA Drug

• 1 other identifier: 22-220
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 6

Brief Summary

The researchers are doing this study to see if early reinfusion of tisagenlecleucel can keep participants in B-CEll ApLasia at 6 months after their first infusion. The researchers will also look at the safety of early reinfusion and how effective it is at treating B-ALL.

Conditions

B-cell Acute Lymphoblastic Leukemia

Keywords

Tisagenlecleucel; Relapsed/Refractory CD19-Positive B-Cell; REinFusion; REFUEL; 22-220

Outcome Measures

Primary Outcomes (1)

• decrease the loss of peripheral BCA rate

  below 10% (from 26% to 9%)

  6 months

Secondary Outcomes (1)

• number and percentage of toxicities with early reinfusion of CAR T cells

  1 year

Study Arms (1)

Tisagenlecleucel

EXPERIMENTAL

Patients will receive reinfusion of tisagenlecleucel on day +30-60 after their initial infusion if meeting eligibility criteria. Tisagenlecleucel is an autologous cellular immunotherapy product that is comprised of CD3+T cells that have undergone ex vivo T cell activation, gene modification, expansion, and formulation in infusible cryomedia.

Biological: Tisagenlecleucel

Interventions

Tisagenlecleucel BIOLOGICAL

Tisagenlecleucel will be infused based on institutional guidelines. Reinfusion of tisagenlecleucel will occur 30-60 days following the first dose.

Tisagenlecleucel

Eligibility Criteria

• Age: 1 Day - 25 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Patients with R/R B-ALL who have received commercial tisagenlecleucel and have (an) additional dose(s) available for early reinfusion
• History of CD19 expressing (in peripheral blood or bone marrow by flow cytometry) BALL prior to tisagenlecleucel infusion
• Peripheral blood B-cell aplasia (BCA) within 14 days prior to reinfusion (See section 13.8: B-cell aplasia will be defined as peripheral blood (PB) absolute B lymphocyte count ≤ 50/μL. If BCA evaluation is repeated at any timepoint prior to reinfusion, it must be negative to proceed with reinfusion
• Minimal residual disease negative complete remission (CR/CRi) in bone marrow within 14 days prior to reinfusion, including resolution of extramedullary disease
• Patients with tisagenlecleucel that is deemed out of specification (OOS) will be permitted on this protocol if the reason for OOS is deemed to not impact the toxicity and efficacy profile of CAR T cell therapy
• °Reasons for product being OOS include cell viability \< 80%, total nucleated cell count \<2 × 10\^9 in leukapheresis product, failed interferon-γ release assay, leukapheresis product collected \>9 months prior, and determination of residual beads \>50 beads per 3 × 10\^6 cells
• Patients age: \< 26 years at time of first tisagenlecleucel order placement
• Recovered from severe toxicities following initial dose of tisagenlecleucel
• CRS
• Neurotoxicity/ICANS
• Adequate organ function at time of treatment is required and is defined:
• Hepatic: Serum bilirubin ≤ 2 mg/dL, unless benign congenital hyperbilirubinemia
• Hepatic: AST and ALT \< 5x the upper limit of normal for age, unless thought to be disease-related
• Renal: Serum creatinine \<1.5x normal for age. If serum creatinine is outside the normal range, then CrCl \> 60 mL/min/1.73m2 (calculated or estimated) or GFR (mL/min/1.72m2 ) \>55% of predicted normal for age
• Age Mean GFR +/-SD (mL/min/1.73 m2)

You may not qualify if:

• Greater than 60 days from first tisagenlecleucel infusion
• Ongoing severe toxicities from initial CAR T cell infusion
• Received non-standard lymphodepleting chemotherapy (LDC) prior to initial tisagenlecleucel dose
• Standard LDC is defined as:
• Fludarabine 30mg/m\^2/dose x 4 doses
• Cyclophosphamide 500mg/m\^2/dose x 2 doses
• Loss of BCA at any timepoint prior to reinfusion
• Clinically significant active infection confirmed by clinical evidence, imaging, or positive laboratory tests (e.g., blood cultures, PCR for DNA/RNA, etc.)
• Patient/parent/guardian unable to give informed consent or unable to comply with the treatment protocol
• Pregnant or lactating women; women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception while taking study treatment and for at least 12 months after the tisagenlecleucel infusion and until CAR T-cells are no longer present by flow cytometry on two consecutive tests.
• Sexually active males, unless they are willing to use a condom during intercourse while taking study treatment and for at least 12 months after the tisagenlecleucel infusion and until CAR T-cells are no longer present by flow cytometry on two consecutive tests.
• Other uncontrolled, symptomatic, intercurrent illness including but not limited to infection, psychiatric illness, or social situations that would limit compliance with study requirements or in the opinion of the PI would pose an unacceptable risk to the subject
• Any other issue which, in the opinion of the treating physician, would make the patient ineligible for the study

Sponsors & Collaborators

• Memorial Sloan Kettering Cancer Center: lead
• Novartis Pharmaceuticals: collaborator

Study Sites (6)

Children's Hospital of Los Angeles (Data Collection Only)

Los Angeles, California, 90027, United States

Location

Stanford University (Data Collection Only)

Stanford, California, 94305, United States

Location

Children's Hospital Colorado (Data Collection Only)

Aurora, Colorado, 80045, United States

Location

Johns Hopkins University (Data Collection Only)

Baltimore, Maryland, 21287, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Cincinnati Children's Hospital Medical Center (Data Collection Only)

Cincinnati, Ohio, 45229, United States

Location

Related Links

• Memorial Sloan Kettering Cancer Center

MeSH Terms

Conditions

Burkitt Lymphoma; Recurrence

Interventions

tisagenlecleucel

Condition Hierarchy (Ancestors)

Epstein-Barr Virus Infections; Herpesviridae Infections; DNA Virus Infections; Virus Diseases; Infections; Tumor Virus Infections; Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Kevin Curran, MD

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 13, 2022
• First Posted: July 15, 2022
• Study Start: July 12, 2022
• Primary Completion (Estimated): July 1, 2027
• Study Completion (Estimated): July 1, 2027
• Last Updated: February 4, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will share

Locations

US (6)