Health Condition 1: C910- Acute lymphoblastic leukemia [ALL]
Conditions
Interventions
Intervention1: Humanized CD19-directed CAR T-cells: HCAR19: A humanized second generation anti-CD19 CAR
construct (HCAR19) with 4-1BB co-stimulatory domain has been designed and developed at IIT-Bomba
Sponsors
Tata Memorial Hospital Research Administrative Council
Eligibility
Inclusion criteria
Inclusion criteria: Disease Criteria: Relapsed or refractory pediatric (3-25) years at screening) B-cell ALL. Relapse for the purpose of this study is defined as Presence of > 5% blasts at screening, and confirmation by FCM, AND Second or subsequent bone marrow (BM) elapse, OR Any BM relapse after allogeneic SCT (must be � 6months from SCT at the time of HCAR19 T-cells infusion: First Relapse will be considered if First Relapse has occurred very early, within 18 months of initial diagnosis Is not in remission after re-induction chemotherapy as defined by FCM MRD First Relapse in High-risk groups such as Ph+ and Ph-like ALL. Refractory B-ALL is defined as: Not achieving an initial CR after 2 cycles of a standard chemotherapy regimen (primary refractory). AND Such patients have received 2 or more lines of second-line or salvage chemotherapy and are still not in FCM based MRD-defined remission. CD19 expression criteria: CD19 tumor expression in bone marrow (BM) or peripheral blood (PB) within 3 months of study entry. Documentation of CD19 expression of >99% of blasts by flowcytometry at ACTREC flow lab at screening. Absence of CD19 negative subclone of any type at time of study entry Host Criteria: Age criteria: Age more than 3 completed years and less than 25 completed years at screening for enrolment on the study. Overall fitness criteria: (Patient must fulfil all criteria) Minimum level of pulmonary reserve defined as grade 95% at room air. Left ventricular ejection fraction > 45% and fractional shortening > 28% confirmed by echocardiography within 3 months of screening. Karnofsky (age >16 years) or Lansky (age 50 at screening. Normal age-adjusted eGFR creatinine clearance at screening. Alanine aminotransferase Adequate organ function. Clinically assessed, with the further investigation if clinically indicated. This will include but not limited to those with the severe systemic compromise of any major organ system as assessed by ejection fraction of For males or females of reproductive potential, has agreed to use effective contraception method during the study for minimum 6 months after study treatment.
Exclusion criteria
Exclusion criteria: Failure to meet any of the inclusion criteria Patients who test positive on urine pregnancy testing and are pregnant or are lactating Isolated extra-medullary relapse Burkitt lymphoma/leukemia Concomitant genetic syndromes associated with bone marrow failure states such as Fanconi anemia, Kostmann syndrome, Schwachmann syndrome or any other BM failure syndromes with the exception of Downs syndrome. Any syndrome with genetic predisposition to cancer eg. Li Fraumeni syndrome Any prior malignancy Active or latent hepatitis B or active hepatitis C detected at screening. Any test in the preceding 8 weeks will be considered valid Any uncontrolled infection at time of screening. Positive HIV test at screening. Grade II to IV graft-versus-host-disease (GVHD)for post Allo-SCT patients. Receiving an investigational medicinal product within 30 days of screening. Treatment with any prior gene therapy product, anti- CD19/anti-CD3 therapy, or any other anti-CD19therapy Medications or treatments that will be excluded: Corticosteroids within 72 hours of HCAR19 T-cell infusion, with the exception of physiologic replacement Allogeneic cellular therapy, such as donor lymphocyte infusion within 6 weeks prior to infusion. GVHD therapies Chemotherapy stopped prior to lymphodepletion based on clearance CNS prophylaxis treatment Active CNS disease, whether established clinically, radiologically, or by CSF studies. Exception would be CNS 2 disease i.e. CSF containing blasts,but < 5 WBCs/microliter. Such patients, with no other evidence of CNS involvement, would be eligible)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| To demonstrate functionality of HCAR19 T-cells in reducing leukemic burden in patients 3 to 25 years of age with relapsed/ refractory B-Cell ALL as a first-in-human pilot study.Timepoint: Active Management of Post Infusion Complications and Mandatory Response Evaluations: Day-0 to Day-30 Observation period: - Active monitoring and assessments for 1 year from enrolment - Follow-up for 10 years from enrolment - After 10 years patients will be advised to follow up as long as alive on as a convenient basis | — |
Secondary
| Measure | Time frame |
|---|---|
| i. To study toxicities of HCAR19 T-cells in the study population ii. To study the persistence, expansion and phenotype of HCAR19 T-cells in the target tissues (blood, bone-marrow, cerebrospinal fluid (CSF), and other extramedullary sites if involved. iii. To study cytokine level and other biomarkers of toxicity and efficacy of infused HCAR19 T-cells iv. To correlate toxicities, efficacy and biomarkers profile with steps and protocols of manufacturing HCAR19 T-cells.Timepoint: Active Management of Post Infusion Complications and Mandatory Response Evaluations: Day-0 to Day-30 Observation period: - Active monitoring and assessments for 1 year from enrolment - Follow-up for 10 years from enrolment - After 10 years patients will be advised to follow up as long as alive on a as convenient basis | — |
Countries
India
Contacts
Public ContactDr Gaurav Narula
Tata Memorial Centre
Outcome results
None listed