Safety and Efficacy of CAR T Cell Therapy in Patients with R/r B-ALL

A Phase I/II Single Arm Study, Safety and Efficacy Assessment of the CD19 CAR T Cell on Pediatric Patients with Relapsing or Refractory B Cell Acute Lymphoblastic Leukemia (r/r B-ALL)

The goal of this clinical trial is to evaluate the safety and efficacy of CD19 CAR-T cells in pediatric patients of all genders, aged 2 to 18 years, with relapsing or refractory B cell acute lymphoblastic leukemia (r/r B-ALL). The main questions it aims to answer are as following:

1. What is the percentage of patients with overall remission rate (ORR) of complete response (CR) or complete remission with incomplete blood count recovery (CRi)?
2. What is the rate of Event-free survival at first month and 2-3 months after intervention?
3. What is the rate of Overall survival at first month and at 3 months after the intervention?

Study Overview

• Status: Recruiting
• Conditions: Relapse/Refractory B-cell Acute Lymphoblastic Leukemia
• Intervention / Treatment: Biological: anti-CD19 CAR T cell therapy

Detailed Description

B-cell acute lymphoblastic leukemia (B-ALL), as the most common type of pediatric tumor, is identified by unregulated cell proliferation of immature lymphoid cells that can infiltrate the bone marrow and blood. Also, relapse and refractory B-ALL (R/R B-ALL) is the main reason of global mortality due to the constraints of combination chemotherapy.

Over the past few years, substantial advancements have been made in treatment of ALL, specifically in the R/R context. Chimeric antigen receptor T (CAR-T) cells are a type of cancer immunotherapy treatment that function through modification of patient T cells to express CAR antigen on their surface. CAR-T cells aimed at CD19 have demonstrated promising activity in treatment of r/r B-ALL. In this study we aim to evaluate safety and efficacy of Anti-CD19 CAR T cell therapy in children with R/R B-ALL.

• Study Type: Interventional
• Enrollment (Estimated): 5
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Setayesh Sadeghi; Phone Number: +989124779968; Email: sadeghi.setayesh@gmail.com

Study Locations

• Iran, Islamic Republic of
  • Tehran, Iran, Islamic Republic of, 1419733151
    • Recruiting
    • Pediatric cell and gene therapy research center, Children medical center
    • Contact: Amir Ali Hamidieh; Phone Number: +989121593270; Email: aahamidieh@tums.ac.ir

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Ages 2 to 18 years with relapsed or refractory CD19+ B-ALL
• Presence of disease in the bone marrow
• Able to tolerate the apheresis process
• Life expectancy > 12 weeks
• Lansky or Karnofsky score > 50%
• At least 7 days passed since the last chemotherapy and the last treatment with corticosteroids
• Informed consent
• Having potential donor for stem cell transplantation

Exclusion Criteria:

• Presence of active malignancy other than the disease under study
• Chloroma and leukemic infiltration on MRI or significant neurological symptoms
• Any CNS disorder
• Presence of active GVHD
• Radiation therapy within last 14 days
• History of Anti-CD19 or Anti-CD20 therapy
• Donor lymphocyte injection or other cell therapy methods within the last 30 days
• Presence of severe active infection
• Organ dysfunction

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Anti-CD19 CAR-T treatment group	Biological: anti-CD19 CAR T cell therapy; Anti-CD19 CAR-T cell therapy for R/R B-ALL pediatric patients. For patients 50 kg and less: 0.2 to 5 in ten to the power of six live CAR+ T cells per kilogram of body weight/ For patients over 50 kg: 0.1 to 2.5 in ten to the power of eight live CAR+ T cells (without considering weight).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Percentage of patients with overall remission rate (ORR) of complete response (CR) or complete remission with incomplete blood count recovery (CRi)	First month and 2-3 months after intervention
Overall survival	First month and 3 months after intervention
Incidence of cytokine release syndrome: grade 3 and 4	First month and 3 months after intervention
Incidence of Immune effector cell-associated neurotoxicity syndrome (ICANS): grade 3 and 4	First month and 3 months after intervention
Event-free survival	First month and 2-3 months after intervention

Secondary Outcome Measures

Outcome Measure	Time Frame
Percentage of patients with overall remission rate (ORR) of complete response (CR) or complete remission with incomplete blood count recovery (CRi)	6 months and 12 months after intervention
Investigation of Minimal residual disease in patient	First month and 2-3 months after intervention
Incidence of cytokine release syndrome: grade 3 and 4	6 months and 12 months after intervention
Incidence of Immune effector cell-associated neurotoxicity syndrome (ICANS): grade 3 and 4	6 months and 12 months after intervention
Incidence of tumor lysis syndrome (TLS)	Months 1, 3, 6, and 12 after the intervention
Incidence of leukopenia	Months 1, 3, 6, and 12 after the intervention
Incidence of infection	Months 1, 3, 6, and 12 after the intervention
Event-free survival	6 months and 12 months after intervention
Overall survival	6 months and 12 months after intervention

Collaborators and Investigators

• Sponsor: Kara Yakhteh Tajhiz Azma Company

Study record dates

Study Major Dates

• Study Start (Actual): May 20, 2024
• Primary Completion (Estimated): September 22, 2026
• Study Completion (Estimated): September 22, 2027

Study Registration Dates

• First Submitted: October 1, 2024
• First Submitted That Met QC Criteria: October 8, 2024
• First Posted (Actual): October 10, 2024

Study Record Updates

• Last Update Posted (Actual): October 10, 2024
• Last Update Submitted That Met QC Criteria: October 8, 2024
• Last Verified: October 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Hematologic Diseases; Leukemia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphoid
• Other Study ID Numbers: IR.NREC.1403.003

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No