Study of Tisagenlecleucel in Chinese Pediatric and Young Adult Subjects With Relapsed or Refractory B-cell ALL
Study Details
Study Description
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)
Condition or Disease | Intervention/Treatment | Phase |
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Phase 2 |
Detailed Description
The study will have the following sequential phases for all subjects:
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Screening
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Pre-Treatment (Cell Product Preparation and Lymphodepleting Chemotherapy)
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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.
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
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Experimental: Tisagenlecleucel 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
A single intravenous (i.v.) infusion of CAR-positive viable T cells.
Other Names:
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Outcome Measures
Primary Outcome Measures
- Overall Remission Rate (ORR) [From first dosing (single administration, Day 1) up to Month 3]
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)
Secondary Outcome Measures
- CR or CRi rate at month 6 [Month 6]
Evaluate the percentage of participants who achieve CR or CRi at Month 6 without SCT after tisagenlecleucel infusion
- CR or CRi rate at Day 28 [Day 28]
Evaluate the percentage of participants who achieve CR or CRi at Day 28 after tisagenlecleucel infusion
- 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]
Evaluate the percentage of participants who achieve a BOR of CR or CRi with a MRD negative bone marrow during the 3 months after tisagenlecleucel infusion
- Duration of remission (DOR) [Average of 60 Months]
DOR, i.e. the time from achievement of CR or CRi, whichever occurs first, to relapse or death due to ALL
- Relapse free survival (RFS) [Avarage of 60 Months]
RFS, i.e. the time from achievement of CR or CRi whichever occurs first to relapse or death due to any cause during CR or CRi
- Event free survival (EFS) [Average of 60 Months]
EFS, i.e. the time from date of Tisagenlecleucel infusion to the earliest of death, relapse or treatment failure
- Overall survival (OS) [Average of 60 Months]
OS, i.e. the time from date of tisagenlecleucel infusion to the date of death due to any reason
- Number of Participants with On-Treatments Adverse Events, Serious Adverse Events, and Deaths [From Screening up to Month 60]
Analysis of absolute and relative frequencies for treatment emergent Adverse Event (AE), Serious Adverse Event (SAE) and Deaths by primary System Organ Class (SOC) parameters.
- In vivo cellular PK profile of tisagenlecleucel [Up to Month 60]
qPCR and flow cytometry will be used to measure tisagenlecleucel transgene concentration in blood, bone marrow and other matrices/tissues
- Serum cytokine [Up to Month 60]
Concentrations of soluble factors (such as IL-10, iFN-y, IL-6) in blood will be summarized by participant and time point
- Levels of pre-existing and treatment induced humoral immunogenicity [Up to Month 60]
The humoral immunogenicity assay measures the antibody titers specific to tisagenlecleucel prior to and following infusion
- Tociluzumab PK [Up to Day 7 after tocilizumab infusion]
Concentrations of tocilizumab
- Levels of prexisting and treatment induced cellular immunogenicity [Up to Month 60]
The cellular immunogenicity assay will assess the presence of T lymphocyte activated by the tisagenlecleucel protein
Eligibility Criteria
Criteria
Key Inclusion Criteria:
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Chinese patients age ≤25 years at the time of informed consent form (ICF) signature.
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Relapsed or refractory B-cell ALL
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2nd or greater bone marrow (BM) relapse OR
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Any BM relapse after allogeneic SCT and must be ≥ 3 months from SCT at the time of screening OR
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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
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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
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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
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For relapsed patients, CD19 tumor expression demonstrated in bone marrow or peripheral blood by flow cytometry within 3 months of screening
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Bone marrow with ≥ 5% lymphoblasts on local morphologic assessment at screening
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Adequate performance status, cardiac, hepatic, renal and pulmonary function at screening
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Must meet the institutional criteria to undergo leukapheresis
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Once all other eligibility criteria are confirmed, must have a leukapheresis material of non-mobilized cells received and accepted for manufacturing.
Key Exclusion Criteria:
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Isolated extra-medullary disease relapse
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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.
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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)
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Prior anti-CD19 directed therapy, gene therapy or adoptive T cell therapy
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CNS involvement by ALL, defined as CNS-2 and CNS-3 disease per National Comprehensive Cancer Network guidelines NCCN 2018 v1
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Active neurological autoimmune or inflammatory disorders (e.g. Guillain-Barre syndrome)
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History or presence of clinically relevant CNS pathology, e.g., epilepsy, paresis, aphasia, stroke, severe brain injuries, cerebellar disease, organic brain syndrome, or psychosis.
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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.
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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
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- Novartis Pharmaceuticals
Investigators
- Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- CCTL019B2210