Phase I Clinical Trial Evaluating Safety of CD19 CAR-T Cells in Patients With Relapsed or Refractory Acute B-cell Lymphoblastic Leukemia (R/R B-ALL)
Trial Snapshot
- Phase
- Phase 1
- Sponsor
- Sabz Biomedicals
- Enrollment
- 22
- Locations
- 2
- Primary Endpoint
- Maximum Tolerated Dose (MTD) and Dose-limiting Toxicities (DLT) of CD19 CAR-T cells
Study Overview
Brief Summary
This is a single-arm, open-label, phase I study (safety and dose escalation) of autologous Chimeric Antigen Receptor (CAR) T-cells targeting CD19 in patients with relapsed/refractory B cell acute lymphoblastic leukemia (ALL).
Detailed Description
In this single-center, open-label, nonrandomized, no control, prospective clinical trial, pediatric or adolescent/young adult patients with CD19+ relapsed or refractory B cell acute lymphoblastic leukemia (R/R B-ALL) will be enrolled.
Eligible patients will receive CAR T product intravenously as a single or split dose following pre-conditioning by a lymphodepleting chemotherapeutic regimen and will then enter a 30-day follow-up period to monitor adverse events using the NCI CTCAE (version 5.0).
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- — to 25 Years (Child, Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •CD19+ ALL patients with any of the following:
- •Relapsed or Refractory CD19 positive B-cell acute lymphoblastic leukemia (R/R B-ALL) A. Primary refractory disease despite at least 2 cycles of an intensive chemotherapy regimen designed to induce remission B. Refractory disease despite salvage therapy C. 2nd or greater relapse D. Any relapse after allogeneic hematopoietic stem cell transplantation
- •Informed consent explained to and signed by patient/parents or legal guardian.
- •The Karnofsky (age ≥10 years)/Lansky (age <10 years) performance status score over 50 points.
- •Expected to survive for more than 3 months.
- •Patients with a history of prior allogeneic hematopoietic stem cell transplant (HSCT) must be at least 3 months from HSCT at the time of CD19 CAR-T cells infusion and also have not received a donor lymphocyte infusion (DLI) within the 28 days prior to apheresis.
- •Important organ function is satisfied: Heart ultrasound indicates cardiac ejection fraction ≥ 50%, no obvious abnormality in ECG; Adequate pulmonary function defined as forced vital capacity (FVC) ≥ 50% of predicted value; or pulse oximetry ≥ 92% on room air if the patient is unable to perform pulmonary function testing; creatinine clearance calculated by Cockcroft-Gault formula ≥ 50 ml/min/1.73m2; Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≤ 5 times the upper limit of normal for age; Total Bilirubin ≤ 3 times the upper limit of normal for age.
- •Absolute lymphocyte count ≥ 0.5 x 10⁹/L.
- •Hemoglobin ≥ 8 g/dl (can be transfused).
- •Platelet count ≥ 20,000/μL (can be transfused).
- •Meets eligibility criteria to undergo autologous apheresis.
Exclusion Criteria
- •Isolated extra-medullary disease relapse.
- •Active CNS involvement of ALL (CNS Grade 3 per National Comprehensive Cancer Network guidelines).
- •Severe, uncontrolled bacterial, fungal or viral infections (Active hepatitis B or C, history of HIV infection)
- •Pre-existing significant neurological disorder.
- •Active significant acute graft versus host disease (GVHD) or moderate/severe chronic GVHD requiring systemic steroids or other immunosuppressants within 4 weeks of enrolment.
- •Pregnant or lactating female.
- •The patient did not agree to use effective contraception during the treatment period and for the following 1 year.
- •A history of other malignant tumors.
- •Receiving systemic steroids therapy exceeding the equivalent of 0.5 mg/ kg/day of methylprednisolone, in the 7 days prior to CAR T-cell infusion
- •Receiving systemic immunosuppressive therapy in the 14 days prior to CAR T-cell infusion
- •Receiving intrathecal chemotherapy in the 7 days prior to CAR T-cell infusion
Arms & Interventions
CD19 CAR-T cells
Pediatric or adolescent/young adult patients with CD19+ relapsed or refractory B cell acute lymphoblastic leukemia (R/R B-ALL)
Intervention: CD19 CAR engineered autologous T-cells (Biological)
CD19 CAR-T cells
Pediatric or adolescent/young adult patients with CD19+ relapsed or refractory B cell acute lymphoblastic leukemia (R/R B-ALL)
Intervention: Cyclophosphamide (Drug)
CD19 CAR-T cells
Pediatric or adolescent/young adult patients with CD19+ relapsed or refractory B cell acute lymphoblastic leukemia (R/R B-ALL)
Intervention: Fludarabine (Drug)
CD19 CAR-T cells
Pediatric or adolescent/young adult patients with CD19+ relapsed or refractory B cell acute lymphoblastic leukemia (R/R B-ALL)
Intervention: Mesna (Drug)
Outcomes
Primary Outcomes
Maximum Tolerated Dose (MTD) and Dose-limiting Toxicities (DLT) of CD19 CAR-T cells
Time Frame: Within 30 days after the last dose of CD19 CAR-T cells
Patients will be continually assessed for unexpected adverse events using the NCI CTCAE (version 5.0) or unexpected early mortality 30 days post-infusion. The primary objectives for the Phase I study portion are to determine the maximum tolerated dose (MTD) and characterize the safety profile and dose-limiting toxicities (DLTs) of treatment with CD19 CAR-T cells in pediatric, adolescent and young adult patient's ≤ 25 years of age, with relapsed/refractory CD19+ ALL.
Secondary Outcomes
- Number of patients who achieve complete morphological remission(Within 30 days post CD19 CAR-T cells)