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

• Status: Active, not recruiting
• Trial end date: 2030-12-01
• Target enrollment: 0
• Participant gender: All

Summary

This study aims to evaluate the safety, efficacy and duration of response of CD19 Chimeric Antigen Receptor (CAR) redirected autologous T-cells in children with high risk, relapsed CD19+ haematological malignancies.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University College, London
• Treatments: Cyclophosphamide; Fludarabine; Fludarabine phosphate

Criteria

Inclusion Criteria:

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

1. Resistant disease (>25% blasts) at end of UKALL 2011 or equivalent induction

2. ALL with persistent high level MRD at 2nd time point of frontline national protocol (currently > 5 x 10-3 at week 14 UKALL2011 or equivalent)

3. 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 Interfant 06)

4. Intermediate risk infant ALL with MRD > 10-3 at end of Interfant06 induction

5. Very early (< 18 months from diagnosis) bone marrow or extramedullary relapse of acute lymphoblastic leukaemia (ALL)

6. Early (within 6 months of finishing therapy) bone marrow, or combined extramedullary relapse of ALL with bone marrow minimal residual disease (MRD) > 10-3 at end of re-induction

7. Any on therapy relapse of ALL in patients age 16-24

8. Any relapse of infant ALL

9. ALL post ≥ 2nd relapse

10. Any refractory relapse of ALL

11. ALL with MRD >10-4 prior to planned stem cell transplant

12. Any relapse of ALL eligible for stem cell transplant but no available HLA matched donor or other contraindication to transplant

13. Any relapse of ALL after stem cell transplant

14. Any relapse of Burkitt's or other CD19+ lymphoma

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

3. Written informed consent

Exclusion Criteria:

• Exclusion Criteria for registration:

1. CD19 negative disease

2. Active hepatitis B, C or HIV infection

3. Oxygen saturation ≤ 90% on air

4. Bilirubin > 3 x upper limit of normal

5. Creatinine > 3 x upper limit of normal

6. Women who are pregnant or lactating

7. Stem Cell Transplant patients only: active acute graft-versus-host disease (GVHD) overall Grade ≥ II (Seattle criteria) or moderate/severe chronic GVHD (NIH consensus criteria) requiring systemic steroids

8. Inability to tolerate leucapheresis

9. Karnofsky (age ≥ 10 years) or Lansky (age < 10) score ≤ 50%

Exclusion criteria for CD19CAR T-cell infusion:

1. Severe intercurrent infection at the time of scheduled CD19CAR T-cell infusion

2. Requirement for supplementary oxygen or active pulmonary infiltrates at the time of scheduled CD19CAR T-cell infusion

3. Allogeneic transplant recipients with active acute GVHD overall grade >2 or moderate/severe chronic GVHD requiring systemic steroids at the time of scheduled CD19CAR T-cell infusion