Study of Tisagenlecleucel in Chinese Pediatric and Young Adult Subjects With Relapsed or Refractory B-cell ALL

NCT04156659 | Withdrawn Phase 2

• 1 other identifier: CCTL019B2210
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

This is a single arm, multi-center, phase II study to evaluate the efficacy and safety of tisagenlecleucel in Chinese pediatric and young adult subjects with relapsed or refractory B-cell acute lymphoblastic leukemia (ALL)

Conditions

B-cell Acute Lymphoblastic Leukemia

Keywords

Relapsed/Refractory B-cell Acute Lymphoblastic Leukemia; ALL; Tisagenlecleucel; CTL019; China

Outcome Measures

Primary Outcomes (1)

• Overall Remission Rate (ORR)

  Evaluate the efficacy of tisagenlecleucel using overall remission rate (ORR) during the 3 months after tisagenlecleucel administration as assessed by the investigator. The ORR is defined as the proportion of subjects with a best overall disease response of Complete Remission (CR) or Complete Remission with Incomplete blood count recovery (CRi)

  From first dosing (single administration, Day 1) up to Month 3

Secondary Outcomes (13)

• CR or CRi rate at month 6

  Month 6

• CR or CRi rate at Day 28

  Day 28

• Best Overall Response (BOR) of CR or CRi with a MRD negative bone marrow

  From first dosing (single administration, Day 1) up to Month 3

• Duration of remission (DOR)

  Average of 60 Months

• Relapse free survival (RFS)

  Avarage of 60 Months

Study Arms (1)

Tisagenlecleucel

EXPERIMENTAL

All patients eligible for treatment with tisagenlecleucel will receive a single dose of tisagenlecleucel. For subjects ≤ 50 kg, tisagenlecleucel will be administered as a single infusion of 0.2 to 5.0 x 10\^6 CAR positive viable T cells per kg body weight. For subjects \> 50 kg, tisagenlecleucel will be administered as a single infusion of 0.1 to 2.5 x 10\^8 CAR positive viable T cells.

Biological: Tisagenlecleucel

Interventions

Tisagenlecleucel BIOLOGICAL

A single intravenous (i.v.) infusion of CAR-positive viable T cells.

Also known as: CTL019

Tisagenlecleucel

Eligibility Criteria

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

You may qualify if:

• Chinese patients age ≤25 years at the time of informed consent form (ICF) signature.
• Relapsed or refractory B-cell ALL
• nd or greater bone marrow (BM) relapse OR
• Any BM relapse after allogeneic SCT and must be ≥ 3 months from SCT at the time of screening OR
• Primary refractory as defined as not achieving a CR after 2 cycles of a standard first line chemotherapy regimen or chemorefractory as defined by not achieving a CR after 1 cycle of standard chemotherapy for relapsed leukemia OR
• Subjects with Ph+ ALL are eligible if they are intolerant to or relapsed/refractory after two lines of tyrosine kinase inhibitor (TKI) therapy, or if TKI therapy is contraindicated OR
• Ineligible for allogeneic SCT because of: comorbid disease; other contraindications to allogeneic SCT conditioning regimen; lack of suitable donor; prior SCT; subject declines allogeneic SCT as a therapeutic option after documented discussion about the role of SCT with a BMT physician not part of the study team
• For relapsed patients, CD19 tumor expression demonstrated in bone marrow or peripheral blood by flow cytometry within 3 months of screening
• Bone marrow with ≥ 5% lymphoblasts on local morphologic assessment at screening
• Adequate performance status, cardiac, hepatic, renal and pulmonary function at screening
• Must meet the institutional criteria to undergo leukapheresis
• Once all other eligibility criteria are confirmed, must have a leukapheresis material of non-mobilized cells received and accepted for manufacturing.

You may not qualify if:

• Isolated extra-medullary disease relapse
• Subjects with concomitant genetic syndromes associated with bone marrow failure states: such as subjects with Fanconi anemia, Kostmann syndrome, Shwachman syndrome or any other known bone marrow failure syndrome. Subjects with Down syndrome will not be excluded.
• Subjects with Burkitt's lymphoma/leukemia (i.e. subjects with mature B-cell ALL, leukemia with B-cell \[sIg positive and kappa or lambda restricted positivity\] ALL, with FAB L3 morphology and /or a MYC translocation)
• Prior anti-CD19 directed therapy, gene therapy or adoptive T cell therapy
• CNS involvement by ALL, defined as CNS-2 and CNS-3 disease per National Comprehensive Cancer Network guidelines NCCN 2018 v1
• Active neurological autoimmune or inflammatory disorders (e.g. Guillain-Barre syndrome)
• History or presence of clinically relevant CNS pathology, e.g., epilepsy, paresis, aphasia, stroke, severe brain injuries, cerebellar disease, organic brain syndrome, or psychosis.
• Investigational medicinal product within the last 30 days or five half-lives (whichever is longer) prior to screening NOTE: Investigational therapies must not be used at any time while on study until the first progression following tisagenlecleucel infusion.
• Previous or concurrent malignancy except for curatively treated non-melanoma skin cancers, in situ carcinoma (e.g. cervix, skin), and cancers in complete remission for at least 3 years and without evidence of recurrence

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

MeSH Terms

Conditions

Burkitt Lymphoma

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

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Study Design

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

Study Record Dates

• First Submitted: October 23, 2019
• First Posted: November 7, 2019
• Study Start: November 30, 2021
• Primary Completion: November 30, 2022
• Study Completion (Estimated): November 30, 2027
• Last Updated: March 9, 2023

Record last verified: 2023-03

Data Sharing

• IPD Sharing: Will share