CARPALL: Immunotherapy With CD19/22 CAR T-cells for CD19+ Haematological Malignancies

This is an interventional treatment trial for Acute Lymphoblastic Leukemia focused on measuring high risk relapsed CD19+ and/or CD22+ hematological malignancies Read More

Inclusion Criteria:

1. Children and young adults (age 24 years or younger) with high risk/relapsed CD19+ and / or CD22+ haematological malignancy:

   A) Resistant disease (>5% blasts) at end of UKALL 2019 guidelines or equivalent induction B) ALL with persisting high level MRD at 2nd time point of frontline national protocol (currently MRD >10-4 at week 14 UKALL2019 guidelines or equivalent).

   C) High risk infant ALL (age < 6 months at diagnosis with MLL gene rearrangement and either presenting white cell count > 300 x 109/L or poor steroid early response (i.e. circulating blast count >1x109/L following 7 day steroid pre-phase of induction as per national guidelines or equivalent) D) Intermediate risk infant ALL with MRD > 10-3 at end of induction following national guidelines or equivalent) E) High risk 1st relapse (as defined by updated IntreALL 2019 classification: bone marrow or combined relapse within 30 months of diagnosis OR any relapse within 18 months of diagnosis) F) Standard risk relapse in patients with high risk cytogenetics (defined as BCR-ABL, KMT2A rearrangement, near-haploidy (<30 chromosomes) and low hypodiploidy (30-39 chromosomes), iAMP21 and TCF3-HLF translocations).

   G) Standard risk relapse with bone marrow minimal residual disease (MRD) > 10-3 at end of re-induction H) Any on therapy relapse in patients age 16-24 I) Any relapse of infant ALL J) ALL post ≥ 2nd relapse K) Any refractory relapse of ALL (defined as > 1% blasts by flow cytometry after a at least 1 cycle of standard chemotherapy) L) ALL with MRD >10-4 prior to planned stem cell transplant M) Any relapse of ALL eligible for stem cell transplant but no available HLA matched donor or other contraindication to transplant N) Any relapse of ALL after stem cell transplant O) Any relapse of Burkitt's or other CD19+ and/or CD22+lymphoma Note patients with isolated CNS relapse meeting one or more of the criteria above are eligible for the study

2. Agreement to have a pregnancy test, use adequate contraception (if applicable)
3. Written informed consent

Exclusion Criteria:

• Exclusion Criteria for registration:

  1. Active Hepatitis B, C or HIV infection
  2. Oxygen saturation ≤ 90% on air
  3. Bilirubin > 3 x upper limit of normal
  4. Creatinine > 3 x upper limit of normal
  5. Women who are pregnant or breastfeeding
  6. Stem Cell Transplant patients only: active significant (overall Grade ≥ II, Seattle criteria) acute GVHD or moderate/ severe chronic GVHD (NIH consensus criteria) requiring systemic steroids.
  7. Inability to tolerate leucapheresis
  8. Karnofsky (age ≥ 10 years) or Lansky (age < 10) score ≤ 50%
  9. Pre-existing significant neurological disorder (other than CNS involvement of underlying haematological malignancy)

Exclusion criteria for CD19/22CAR T-cell infusion:

1. Severe intercurrent infection at the time of scheduled CD19/22 CAR T-cell infusion
2. Requirement for supplementary oxygen or active pulmonary infiltrates at the time of scheduled CD19/22 CAR T-cell infusion
3. Allogeneic transplant recipients with active significant acute GVHD overall grade ≥II or moderate/severe chronic GVHD requiring systemic steroids at the time of scheduled CD19/22 CAR T-cell infusion. Note: Such patients will be excluded until the patient is GVHD free and off steroids