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

NCT05038696 | Recruiting Phase 1 DMC

• 1 other identifier: 2020/00865
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

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).

Conditions

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

Outcome Measures

Primary Outcomes (1)

• 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.

  30 days

Secondary Outcomes (2)

• 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.

  30 days

• 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

  1 month to 5 years

Study Arms (1)

Single arm

EXPERIMENTAL

Single arm Phase I Clinical Trial

Biological: CAR T-cell therapy

Interventions

CAR T-cell therapy BIOLOGICAL

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.

Single arm

Eligibility Criteria

• Age: 6 Months - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• National University Hospital, Singapore: lead

Study Sites (1)

Allen Yeoh Eng Juh

Singapore, 119228, Singapore

RECRUITING

MeSH Terms

Conditions

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Interventions

Immunotherapy, Adoptive

Condition Hierarchy (Ancestors)

Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Adoptive Transfer; Immunization, Passive; Immunization; Immunotherapy; Immunomodulation; Biological Therapy; Therapeutics; Immunologic Techniques; Investigative Techniques

Study Officials

• Allen Yeoh, M.D

  National University Hospital, Singapore

  PRINCIPAL INVESTIGATOR

• Dario Campana, M.D, PhD

  National University of Singapore

  STUDY DIRECTOR

Central Study Contacts

Allen Yeoh, M.D

CONTACT

+65 6772 2002; paeyej@nus.edu.sg

Study Design

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

Study Record Dates

• First Submitted: May 26, 2021
• First Posted: September 9, 2021
• Study Start: April 28, 2021
• Primary Completion: May 1, 2026
• Study Completion (Estimated): August 1, 2026
• Last Updated: September 9, 2021

Record last verified: 2021-04

Data Sharing

• IPD Sharing: Will not share

Locations

SG (1)