search
Back to results

ALaCART-B: Acute Leukemia and Chimeric Antigen Receptor-T Cell Therapy for B-lymphoblastic Leukemia. (ALaCART)

Primary Purpose

Lymphoblastic Leukemia, Acute, Childhood, Lymphoblastic Leukemia, Lymphoblastic Leukemia, Acute Adult

Status
Recruiting
Phase
Phase 1
Locations
Singapore
Study Type
Interventional
Intervention
CAR T-cell therapy
Sponsored by
National University Hospital, Singapore
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Lymphoblastic Leukemia, Acute, Childhood focused on measuring B-ALL, CAR-T cell therapy, CAR T-cell therapy

Eligibility Criteria

6 Months - 80 Years (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Fulfil the Diagnosis/ Disease define as:

    1. Relapsed B-cell acute lymphoblastic leukaemia/ lymphoma as defined by:

      Bone marrow disease = or > 0.01% by MRD as determined by flow cytometry Or CNS disease as defined as > 5 WBCs in CSF by morphology, or flow cytometric or molecular evidence of blasts or biopsy proven recurrence in the eye or brain.

      Or Extramedullary relapse as defined by morphological evidence of blasts in the testis or any other extramedullary sites

    2. Induction failure as defined by Day 33/ End of induction:

      MRD ≥ 1% by flow cytometry on the Ma-Spore ALL 2020 protocol Or Failure to achieve morphological remission defined as > 5% blasts after standard induction chemotherapy

    3. Refractory disease as defined by:

      MRD ≥ 0.01% by flow cytometry or molecular methods during 2 or more timepoints after induction therapy

    4. Any high risk features including :

      BCR-ABL1, BCR-ABL1-like, - ABL1-r, PDGFRB-r, TCF3-HLF, MLL-r, hypodiploid ALL (< 45 chromosomes), p53 pathogenic mutation as defined by RNA Seq or other molecular methods.

    5. Patients who are unable to tolerate standard chemotherapy due to significant toxicity as well as other comorbidities
  • Minimum level of pulmonary reserve defined as grade ≤ 1 dyspnoea and oxygen saturation of > 95% on room air
  • Left ventricular systolic function ≥ 28% confirmed by echocardiogram, or left ventricular ejection fraction ≥ 45% confirmed by echocardiogram within 3 months of screening
  • Karnofsky (age ≥ 16 years) or Lansky (age < 16 years) performance status ≥ 50 at screening
  • Normal Age-adjusted eGFR Creatinine Clearance within 3 months of screening
  • Alanine aminotransferase ≤ 5 times the upper limit of normal for age
  • Patients with > 99.9% of CD19 expression on blast cells will be eligible for anti-CD19 CAR T-cell infusion.
  • Patients with partial or absent CD19 expression (< 99.9%) on blast cells will be eligible to receive combinations of other CAR T-cells depending on the pattern of antigen expression.

Exclusion Criteria:

  • Failure to meet any of the inclusion criteria.
  • Patients who test positive on urine pregnancy testing and are pregnant or are lactating
  • Concomitant genetic syndromes associated with BM failure states, such as Fanconi anaemia, Kostmann syndrome, Schwachman syndrome, or any other BM failure syndrome with the exception of Down syndrome
  • Prior malignancy, except carcinoma in situ of the skin or cervix treated with curative intent and no evidence of active disease
  • Active or latent hepatitis B or active hepatitis C within 8 weeks of screening, or any uncontrolled infection at screening
  • Positive HIV test within 8 weeks of screening
  • Grade 2 to 4 acute graft-vs-host disease (GVHD) or extensive chronic GVHD
  • Received an investigational medicinal product within 30 days of screening
  • Persistent disease or relapse after other forms of CAR-T cell therapy.

Sites / Locations

  • Allen Yeoh Eng JuhRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Single arm

Arm Description

Single arm Phase I Clinical Trial

Outcomes

Primary Outcome Measures

Proportion of participant who are flow cytometry minimal residual disease (MRD) negative at the end of 1 month after CAR T-cell infusion.
MRD levels will be determined by flow cytometry, The target sensitivity of flow MRD is <0.01% when available.

Secondary Outcome Measures

Proportion of participant who are minimal residual disease (MRD) negative with molecular base assay at the end of 1 month after CAR T-cell infusion.
MRD levels will be determined by molecular based MRD. PCR and oncogene fusion transcript (OFT).
Proportion of patient who shows CAR T-cell persistence and presence of B-cell aplasia by immunophenotyping using flow cytometry in bone marrow, peripheral blood and CSF samples at multiple study time points following CAR T cell infusion
Flow cytometry will be performed on bone marrow, peripheral blood and CSF samples at multiple study time points following CAR T cell infusion

Full Information

First Posted
May 26, 2021
Last Updated
September 7, 2021
Sponsor
National University Hospital, Singapore
search

1. Study Identification

Unique Protocol Identification Number
NCT05038696
Brief Title
ALaCART-B: Acute Leukemia and Chimeric Antigen Receptor-T Cell Therapy for B-lymphoblastic Leukemia.
Acronym
ALaCART
Official Title
Chimeric-Antigen Receptor (CAR) T-Cell Therapy Using Multiple CARs and Cell Marker Profiling in High Risk and Relapsed/ Refractory B-Lineage Acute Lymphoblastic Leukaemia
Study Type
Interventional

2. Study Status

Record Verification Date
April 2021
Overall Recruitment Status
Recruiting
Study Start Date
April 28, 2021 (Actual)
Primary Completion Date
May 1, 2026 (Anticipated)
Study Completion Date
August 1, 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National University Hospital, Singapore

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
The objective of this study is to assess the safety and efficacy of a immunophenotype-adapted approach using CAR T-cells in patients with high-risk, refractory or relapsed B-lineage acute lymphoblastic leukemia (B-ALL).
Detailed Description
Patients will receive CART-cells with one or more specificities according to the phenotypic profile of the leukemic cells in each individual patient. This will allow targeting the entire leukemia cell population to induce deeper and more durable remissions. Although it would be possible to administer CART-cells targeting all possible antigens to all patients, this indiscriminate approach would increase the CAR T-cell dose and hence, the risk of toxicity in patients that could be effectively treated with a lower, less toxic, CAR T-cell dose. Moreover, the cost of the procedure increases proportionally with the number of CAR T-cells used, limiting our capacity to enrol other patients. Reducing the number of CART-cells below the dose that we set, will inevitably increase the risk of treatment failure, according to the literature and our own experience.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Lymphoblastic Leukemia, Acute, Childhood, Lymphoblastic Leukemia, Lymphoblastic Leukemia, Acute Adult, Lymphoblastic Leukemia in Children, CAR, CAR T-Cell-Related Encephalopathy Syndrome
Keywords
B-ALL, CAR-T cell therapy, CAR T-cell therapy

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
40 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Single arm
Arm Type
Experimental
Arm Description
Single arm Phase I Clinical Trial
Intervention Type
Biological
Intervention Name(s)
CAR T-cell therapy
Intervention Description
This is a single-centre, phase I study to determine the efficacy and safety of CAR T-cell therapy in patients with high-risk B-ALL, refractory or relapsed B-ALL.
Primary Outcome Measure Information:
Title
Proportion of participant who are flow cytometry minimal residual disease (MRD) negative at the end of 1 month after CAR T-cell infusion.
Description
MRD levels will be determined by flow cytometry, The target sensitivity of flow MRD is <0.01% when available.
Time Frame
30 days
Secondary Outcome Measure Information:
Title
Proportion of participant who are minimal residual disease (MRD) negative with molecular base assay at the end of 1 month after CAR T-cell infusion.
Description
MRD levels will be determined by molecular based MRD. PCR and oncogene fusion transcript (OFT).
Time Frame
30 days
Title
Proportion of patient who shows CAR T-cell persistence and presence of B-cell aplasia by immunophenotyping using flow cytometry in bone marrow, peripheral blood and CSF samples at multiple study time points following CAR T cell infusion
Description
Flow cytometry will be performed on bone marrow, peripheral blood and CSF samples at multiple study time points following CAR T cell infusion
Time Frame
1 month to 5 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
6 Months
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Fulfil the Diagnosis/ Disease define as: Relapsed B-cell acute lymphoblastic leukaemia/ lymphoma as defined by: Bone marrow disease = or > 0.01% by MRD as determined by flow cytometry Or CNS disease as defined as > 5 WBCs in CSF by morphology, or flow cytometric or molecular evidence of blasts or biopsy proven recurrence in the eye or brain. Or Extramedullary relapse as defined by morphological evidence of blasts in the testis or any other extramedullary sites Induction failure as defined by Day 33/ End of induction: MRD ≥ 1% by flow cytometry on the Ma-Spore ALL 2020 protocol Or Failure to achieve morphological remission defined as > 5% blasts after standard induction chemotherapy Refractory disease as defined by: MRD ≥ 0.01% by flow cytometry or molecular methods during 2 or more timepoints after induction therapy Any high risk features including : BCR-ABL1, BCR-ABL1-like, - ABL1-r, PDGFRB-r, TCF3-HLF, MLL-r, hypodiploid ALL (< 45 chromosomes), p53 pathogenic mutation as defined by RNA Seq or other molecular methods. Patients who are unable to tolerate standard chemotherapy due to significant toxicity as well as other comorbidities Minimum level of pulmonary reserve defined as grade ≤ 1 dyspnoea and oxygen saturation of > 95% on room air Left ventricular systolic function ≥ 28% confirmed by echocardiogram, or left ventricular ejection fraction ≥ 45% confirmed by echocardiogram within 3 months of screening Karnofsky (age ≥ 16 years) or Lansky (age < 16 years) performance status ≥ 50 at screening Normal Age-adjusted eGFR Creatinine Clearance within 3 months of screening Alanine aminotransferase ≤ 5 times the upper limit of normal for age Patients with > 99.9% of CD19 expression on blast cells will be eligible for anti-CD19 CAR T-cell infusion. Patients with partial or absent CD19 expression (< 99.9%) on blast cells will be eligible to receive combinations of other CAR T-cells depending on the pattern of antigen expression. Exclusion Criteria: Failure to meet any of the inclusion criteria. Patients who test positive on urine pregnancy testing and are pregnant or are lactating Concomitant genetic syndromes associated with BM failure states, such as Fanconi anaemia, Kostmann syndrome, Schwachman syndrome, or any other BM failure syndrome with the exception of Down syndrome Prior malignancy, except carcinoma in situ of the skin or cervix treated with curative intent and no evidence of active disease Active or latent hepatitis B or active hepatitis C within 8 weeks of screening, or any uncontrolled infection at screening Positive HIV test within 8 weeks of screening Grade 2 to 4 acute graft-vs-host disease (GVHD) or extensive chronic GVHD Received an investigational medicinal product within 30 days of screening Persistent disease or relapse after other forms of CAR-T cell therapy.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Allen Yeoh, M.D
Phone
+65 6772 2002
Email
paeyej@nus.edu.sg
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Allen Yeoh, M.D
Organizational Affiliation
National University Hospital, Singapore
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Dario Campana, M.D, PhD
Organizational Affiliation
National University of Singapore
Official's Role
Study Director
Facility Information:
Facility Name
Allen Yeoh Eng Juh
City
Singapore
ZIP/Postal Code
119228
Country
Singapore
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Allen Yeoh, M.D
Phone
(+65) 6772 2002
Email
paeyej@nus.edu.sg
First Name & Middle Initial & Last Name & Degree
Zhiwei Chen, BSc.
Phone
(+65) 6772 4406
Email
chen.zhiwei@nus.edu.sg
First Name & Middle Initial & Last Name & Degree
Bernice Oh, M.D
First Name & Middle Initial & Last Name & Degree
Noriko Shimasaki, M.D, PhD
First Name & Middle Initial & Last Name & Degree
Michelle Poon, M.D
First Name & Middle Initial & Last Name & Degree
Esther Chan, M.D
First Name & Middle Initial & Last Name & Degree
Elaine Coustan-Smith, MS

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

ALaCART-B: Acute Leukemia and Chimeric Antigen Receptor-T Cell Therapy for B-lymphoblastic Leukemia.

We'll reach out to this number within 24 hrs