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

A Phase II, Single Arm, Multi-center Trial to Evaluate the Efficacy and Safety of Tisagenlecleucel in Chinese Pediatric and Young Adult Patients With Relapsed or Refractory B-cell Acute Lymphoblastic Leukemia

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)

The study will have the following sequential phases for all subjects:

• Screening
• Pre-Treatment (Cell Product Preparation and Lymphodepleting Chemotherapy)
• Treatment and Follow-up Tisagenlecleucel infusion should occur within 16 weeks of informed consent. The total duration of the study is 5 years. After tisagenlecluecel infusion, efficacy will be assessed monthly for the first 6 months, then quarterly up to 2 years and semi-annually afterwards up to 5 years, or until the subject relapses.

Key Inclusion Criteria:

1. Chinese patients age ≤25 years at the time of informed consent form (ICF) signature.

2. Relapsed or refractory B-cell ALL

   1. 2nd or greater bone marrow (BM) relapse OR
   2. Any BM relapse after allogeneic SCT and must be ≥ 3 months from SCT at the time of screening OR
   3. 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
   4. 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
   5. 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

3. For relapsed patients, CD19 tumor expression demonstrated in bone marrow or peripheral blood by flow cytometry within 3 months of screening

4. Bone marrow with ≥ 5% lymphoblasts on local morphologic assessment at screening

5. Adequate performance status, cardiac, hepatic, renal and pulmonary function at screening

6. Must meet the institutional criteria to undergo leukapheresis

7. Once all other eligibility criteria are confirmed, must have a leukapheresis material of non-mobilized cells received and accepted for manufacturing.

Key Exclusion Criteria:

1. Isolated extra-medullary disease relapse
2. 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.
3. 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)
4. Prior anti-CD19 directed therapy, gene therapy or adoptive T cell therapy
5. CNS involvement by ALL, defined as CNS-2 and CNS-3 disease per National Comprehensive Cancer Network guidelines NCCN 2018 v1
6. Active neurological autoimmune or inflammatory disorders (e.g. Guillain-Barre syndrome)
7. History or presence of clinically relevant CNS pathology, e.g., epilepsy, paresis, aphasia, stroke, severe brain injuries, cerebellar disease, organic brain syndrome, or psychosis.
8. 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.
9. 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