CD19 Targeted CAR T Cell Therapy in Patients With Relapsed/ Refractory B Cell Acute Lymphoblastic Leukaemia (ALL)

NCT04653493 | Unknown Phase 1 DMC

• 1 other identifier: CD19 CAR T Cells for R/R ALL
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 2

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).

Conditions

Relapsed B Cell Acute Lymphoblastic Leukemia (ALL); Refractory B Cell Acute Lymphoblastic Leukemia (ALL)

Keywords

CD19+ B-cell Acute Lymphoblastic Leukemia; CAR T cell; Relapsed/Refractory B cell acute lymphoblastic leukemia

Outcome Measures

Primary Outcomes (1)

• Maximum Tolerated Dose (MTD) and Dose-limiting Toxicities (DLT) 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.

  Within 30 days after the last dose of CD19 CAR-T cells

Secondary Outcomes (1)

• Number of patients who achieve complete morphological remission

  Within 30 days post CD19 CAR-T cells

Study Arms (1)

CD19 CAR-T cells

EXPERIMENTAL

Pediatric or adolescent/young adult patients with CD19+ relapsed or refractory B cell acute lymphoblastic leukemia (R/R B-ALL)

Biological: CD19 CAR engineered autologous T-cells; Drug: Cyclophosphamide; Drug: Fludarabine; Drug: Mesna

Interventions

CD19 CAR engineered autologous T-cells BIOLOGICAL

Given IV Following preconditioning with lymphodepleting chemotherapy (cyclophosphamide and fludarabine) patients will be treated with CD19 Chimeric Antigen Receptor (CAR) T cells as a single or split dose (day 0, 1 and 2, CAR cells will be intravenously infused at the 10%, 30% and 60% ratio respectively). Dosing of CD19 CAR-T cells will follow a dose-escalation schema, with dose changes based on dose-limiting toxicities.

CD19 CAR-T cells

Cyclophosphamide DRUG

Given IV

CD19 CAR-T cells

Fludarabine DRUG

Given IV

CD19 CAR-T cells

Mesna DRUG

Given IV

CD19 CAR-T cells

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Sabz Biomedicals: lead
• Gene Therapy Research Center, Shariati Hospital, Tehran University of Medical Sciences, Iran: collaborator
• Research Institute for Oncology- Hematology and Cell Therapy (RIOHCT), Tehran University of Medical Sciences, Iran: collaborator

Study Sites (2)

Gene therapy research center, Shariati hospital, Tehran university of medical sciences, Iran

Tehran, Iran

Location

Research Institute for Oncology- Hematology and Cell Therapy (RIOHCT), Tehran University of Medical Sciences

Tehran, Iran

Location

MeSH Terms

Conditions

Burkitt Lymphoma

Interventions

Cyclophosphamide; fludarabine; Mesna

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

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Alkanesulfonates; Alkanesulfonic Acids; Alkanes; Hydrocarbons, Acyclic; Sulfhydryl Compounds; Sulfur Compounds; Sulfonic Acids; Sulfur Acids

Study Officials

• Tahereh Rostami, M.D

  Research Institute for Oncology- Hematology and Cell Therapy (RIOHCT), Tehran University of Medical Sciences, Tehran, Iran

  PRINCIPAL INVESTIGATOR

• Naser Ahmadbeigi, PhD

  Gene Therapy Research Center, Shariati hospital, Tehran University of Medical Sciences, Tehran, Iran

  STUDY DIRECTOR

Central Study Contacts

Tahereh Rostami, M.D

CONTACT

+9821-88004140; trostami@sina.tums.ac.ir

Naser Ahmadbeigi, PhD

CONTACT

+9821-82415103; n-ahmadbeigi@sina.tums.ac.ir

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 22, 2020
• First Posted: December 4, 2020
• Study Start: August 1, 2021
• Primary Completion: August 1, 2024
• Study Completion: August 1, 2024
• Last Updated: March 19, 2021

Record last verified: 2021-03

Locations

IR (2)