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

Primary Purpose

Relapsed B Acute Lymphoblastic Leukaemia, Refractory B Acute Lymphoblastic Leukaemia

Status
Recruiting
Phase
Phase 2
Locations
Malaysia
Study Type
Interventional
Intervention
CD19 CAR-T CELLS
Cyclophosphamide
Fludarabine
Sponsored by
National University of Malaysia
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Relapsed B Acute Lymphoblastic Leukaemia

Eligibility Criteria

13 Years - 65 Years (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • UKM Medical CentreRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

CD19 CAR-T CELLS

Arm Description

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

Outcomes

Primary Outcome Measures

Overall response rate (ORR)
Overall Response Rate (ORR) defined as Complete Response (CR) and CR with incomplete blood recovery (CRi) according to WHO criteria.
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.
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.

Secondary Outcome Measures

Overall survival (OS)
Overall Survival (OS) defined as the time from treatment to the date of death due to any cause.
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.
Time to next treatment (TTNT)
Time To Next Treatment (TTNT) defined as the end of study treatment until the institution of the next therapy.
Percentage of adverse events
Percentage of participants with adverse events

Full Information

First Posted
April 22, 2019
Last Updated
May 2, 2019
Sponsor
National University of Malaysia
Collaborators
Gaia Science
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1. Study Identification

Unique Protocol Identification Number
NCT03937544
Brief Title
Intravenous Autologous CD19 CAR-T Cells for R/R B-ALL
Official Title
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
Study Type
Interventional

2. Study Status

Record Verification Date
May 2019
Overall Recruitment Status
Recruiting
Study Start Date
March 19, 2019 (Actual)
Primary Completion Date
March 18, 2024 (Anticipated)
Study Completion Date
March 18, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
National University of Malaysia
Collaborators
Gaia Science

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Relapsed B Acute Lymphoblastic Leukaemia, Refractory B Acute Lymphoblastic Leukaemia

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2, Phase 3
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
10 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
CD19 CAR-T CELLS
Arm Type
Experimental
Arm Description
A conditioning chemotherapy regiment of fludarabine and cyclophosphamide will be administered followed by a single infusion of CAR transduced autologous T cells administered intravenously.
Intervention Type
Biological
Intervention Name(s)
CD19 CAR-T CELLS
Intervention Description
CD19 CAR-T cells will be administered after completion of the chemotherapy.
Intervention Type
Drug
Intervention Name(s)
Cyclophosphamide
Intervention Description
Patients will receive lymphodepleting chemotherapies consisting Cyclophosphamide 250mg/m2/day IV(Day -5, Day -4, Day -3 ).
Intervention Type
Drug
Intervention Name(s)
Fludarabine
Intervention Description
Patients will receive lymphodepleting chemotherapies consisting of Fludarabine 25mg/m2/day IV (Day -5, Day -4, Day -3 ).
Primary Outcome Measure Information:
Title
Overall response rate (ORR)
Description
Overall Response Rate (ORR) defined as Complete Response (CR) and CR with incomplete blood recovery (CRi) according to WHO criteria.
Time Frame
Participants will be followed for the duration of the treatment, with an expected average of 3 months.
Title
Complete response (CR)
Description
Duration of response defined from the time when criteria for response (CR or CRi) are met to the first documentation of relapse or progression.
Time Frame
12 Months
Title
CR with incomplete blood recovery (CRi).
Description
Duration of response defined from the time when criteria for response (CR or CRi) are met to the first documentation of relapse or progression.
Time Frame
12 Months
Secondary Outcome Measure Information:
Title
Overall survival (OS)
Description
Overall Survival (OS) defined as the time from treatment to the date of death due to any cause.
Time Frame
12 Months, 24 Months
Title
Progression free survival (PFS)
Description
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.
Time Frame
12 Months, 24 Months
Title
Time to next treatment (TTNT)
Description
Time To Next Treatment (TTNT) defined as the end of study treatment until the institution of the next therapy.
Time Frame
12 Months, 24 Months
Title
Percentage of adverse events
Description
Percentage of participants with adverse events
Time Frame
30 days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
13 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
S Fadilah Abdul Wahid, MD, DrIntMed, PhD
Phone
+60391456450
Email
sfadilah@ppukm.ukm.edu.my
Facility Information:
Facility Name
UKM Medical Centre
City
Bandar Tun Razak
State/Province
Kuala Lumpur
ZIP/Postal Code
56000
Country
Malaysia
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
S Fadilah Abdul Wahid, MD, DrIntMed, PhD
Phone
+60391456450
Email
sfadilah@ppukm.ukm.edu.my
First Name & Middle Initial & Last Name & Degree
Wan Fariza Wan Jamaludin, MD,DrIntMed
Phone
+60391457709
Email
wanfariza@ppukm.ukm.edu.my

12. IPD Sharing Statement

Plan to Share IPD
Undecided

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

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