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

Inclusion Criteria26

• 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.
• 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.