Intravenous Autologous CD19 CAR-T Cells for R/R B-ALL

A Phase II/III Prospective, Open Label Study to Evaluate Safety and Efficacy of Intravenous Autologous CD19 CAR-T Cells for Relapsed/ Refractory B-Acute Lymphoblastic Leukaemia

This is Phase II / III, Prospective, single arm, Open Label Study to Evaluate Safety and Efficacy of Intravenous Autologous CD19 CAR-T Cells for Relapsed / Refractory B-Acute Lymphoblastic Leukaemia

Study Overview

• Status: Recruiting
• Conditions: Relapsed B Acute Lymphoblastic Leukaemia; Refractory B Acute Lymphoblastic Leukaemia
• Intervention / Treatment: Biological: CD19 CAR-T CELLS; Drug: Cyclophosphamide; Drug: Fludarabine

• Study Type: Interventional
• Enrollment (Estimated): 10
• Phase: Phase 2; Phase 3

Contacts and Locations

• Study Contact: Name: S Fadilah Abdul Wahid, MD, DrIntMed, PhD; Phone Number: +60391456450; Email: sfadilah@ppukm.ukm.edu.my

Study Locations

• Malaysia
  • Kuala Lumpur
    • Bandar Tun Razak, Kuala Lumpur, Malaysia, 56000
      • Recruiting
      • UKM Medical Centre
      • Contact: S Fadilah Abdul Wahid, MD, DrIntMed, PhD; Phone Number: +60391456450; Email: sfadilah@ppukm.ukm.edu.my
      • Contact: Wan Fariza Wan Jamaludin, MD,DrIntMed; Phone Number: +60391457709; Email: wanfariza@ppukm.ukm.edu.my

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 13 years to 65 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients with relapsed/refractory B-ALL in accordance with World Health Organization (WHO) classification by virtue of BM morphology, flow cytometry, cytogenetics and molecular genetics
• Age between ≥13 to ≤ 65 years
• No detectable leukaemia in the CSF (CNS-1)
• CNS leukaemia without clinically evident neurological symptoms (CNS-2; with <5 WBC per μL and cytology positive for blasts)
• Adequate organ function as defined by a creatinine clearance > 50 ml/min, serum total bilirubin < 5 times the normal value, left ventricular ejection fraction > 40%
• ECOG performance status ≤ 2
• Life expectancy > 3 months
• Post allogeneic HSCT must be ≥ Day +100 with no evidence of active GVHD and not receiving immunosuppression
• Female patients of child bearing age must have negative pregnancy test and is on highly effective contraception methods
• Male patients must use highly effective contraception methods

Exclusion Criteria:

• Patients with CNS-3 leukaemia.
• Active cancer (other than B-ALL).
• Evidence of severe lung, heart (NYHA class III/IV, arrhythmia, AV block, uncontrolled hypertension), liver, or renal failure or severe neurologic disorder.
• Presence of active autoimmune disease or atopic allergy.
• HIV serology positivity.
• Active Hepatitis B or C infection as evidenced by quantitative viral PCR assay.
• Uncontrolled sepsis
• Pregnant / nursing female.
• Ongoing prednisolone > 1mg/kg daily or equivalent.
• Chemotherapy immunotherapy in the recent 4 weeks such as allogeneic cellular therapy weeks, anti-GVHD therapy.

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: CD19 CAR-T CELLS; A conditioning chemotherapy regiment of fludarabine and cyclophosphamide will be administered followed by a single infusion of CAR transduced autologous T cells administered intravenously.

Biological: CD19 CAR-T CELLS; CD19 CAR-T cells will be administered after completion of the lymphodepletion chemotherapy.; Drug: Cyclophosphamide; Patients will receive lymphodepleting chemotherapy consisting of Cyclophosphamide 250 - 300 mg/m2/day IV(Day -5, Day -4, Day -3 ).; Drug: Fludarabine; Patients will receive lymphodepleting chemotherapy consisting of Fludarabine 25-30 mg/m2/day IV (Day -5, Day -4, Day -3 ).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall response rate (ORR)	Overall Response Rate (ORR) defined as Complete Response (CR) and CR with incomplete blood recovery (CRi) according to WHO criteria.	Participants will be followed for the duration of the treatment, with an expected average of 3 months.
Complete response (CR)	Duration of response defined from the time when criteria for response (CR or CRi) are met to the first documentation of relapse or progression.	12 Months
CR with incomplete blood recovery (CRi).	Duration of response defined from the time when criteria for response (CR or CRi) are met to the first documentation of relapse or progression.	12 Months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival (OS)	Overall Survival (OS) defined as the time from treatment to the date of death due to any cause.	12 Months, 24 Months
Progression free survival (PFS)	Progression Free Survival (PFS) defined as the time from treatment to first documentation of objective leukemic progression (date of leukaemia assessment documenting progressive disease) or to death due to any cause. Progression is assessed by BM biopsy or CSF analysis according to NCCN criteria. It is assessed at Day 30 and monthly thereafter, or earlier if clinically indicated.	12 Months, 24 Months
Time to next treatment (TTNT)	Time To Next Treatment (TTNT) defined as the end of study treatment until the institution of the next therapy.	12 Months, 24 Months
Percentage of adverse events	Percentage of participants with adverse events	30 days

Collaborators and Investigators

• Sponsor: National University of Malaysia
• Collaborators: Gaia Science

Study record dates

Study Major Dates

• Study Start (Actual): March 19, 2019
• Primary Completion (Estimated): January 18, 2027
• Study Completion (Estimated): March 18, 2027

Study Registration Dates

• First Submitted: April 22, 2019
• First Submitted That Met QC Criteria: May 1, 2019
• First Posted (Actual): May 3, 2019

Study Record Updates

• Last Update Posted (Actual): May 29, 2025
• Last Update Submitted That Met QC Criteria: May 22, 2025
• Last Verified: May 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Immune System Diseases; Neoplasms by Histologic Type; Hematologic Diseases; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Leukemia; Leukemia, Lymphoid; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antirheumatic Agents; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Cyclophosphamide; Fludarabine
• Other Study ID Numbers: JEP-2019-003; FF-2019-138 (Other Identifier: UKM Medical Centre)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No