CAR T-cell therapy for high-risk B-lymphoblastic leukemia
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
This study is testing a personalized CAR T-cell therapy for people with high-risk B-lymphoblastic leukemia to see if it can help them achieve longer-lasting remissions while keeping side effects low.
Quick facts
| Phase | Phase 1 |
|---|---|
| Study type | Interventional |
| Enrollment | 40 (estimated) |
| Ages | 6 Months to 80 Years |
| Sex | All |
| Sponsor | National University Hospital, Singapore Academic / other |
| Drugs / interventions | CAR T, CAR-T, chemotherapy, CART |
| Locations | 1 site (Singapore) |
| Trial ID | NCT05038696 on ClinicalTrials.gov |
What this trial studies
This study evaluates the safety and effectiveness of a personalized CAR T-cell therapy approach for patients with high-risk, refractory, or relapsed B-lineage acute lymphoblastic leukemia (B-ALL). Patients will receive CAR T-cells tailored to the specific phenotypic profile of their leukemia cells, aiming to target the entire leukemia population for deeper and more durable remissions. The study seeks to balance efficacy and safety by avoiding unnecessary toxicity associated with higher doses of CAR T-cells. By optimizing the treatment based on individual patient profiles, the study aims to improve outcomes while managing costs and risks.
Who should consider this trial
Good fit: Ideal candidates include individuals with relapsed or refractory B-cell acute lymphoblastic leukemia who have specific high-risk features.
Not a fit: Patients with early-stage or non-refractory B-ALL may not benefit from this targeted CAR T-cell therapy.
Why it matters
Potential benefit: If successful, this approach could lead to improved remission rates and overall survival for patients with high-risk B-ALL.
How similar studies have performed: Other studies have shown promising results with CAR T-cell therapies in similar patient populations, indicating potential for success in this novel approach.
Eligibility criteria
Show full inclusion / exclusion criteria
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.
Where this trial is running
Singapore
- Allen Yeoh Eng Juh — Singapore, Singapore (Recruiting)
Study contacts
- Principal investigator: Allen Yeoh, M.D — National University Hospital, Singapore
- Study coordinator: Allen Yeoh, M.D
- Email: paeyej@nus.edu.sg
- Phone: +65 6772 2002
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.