CARPALL: Immunotherapy with CD19+CD22 CAR T-cells for CD19+ and CD22+ Acute Lymphoblastic Leukaemia
Immunotherapy with CD19+CD22 CAR Redirected T-cells for High Risk/relapsed Paediatric CD19+ and CD22+ Acute Lymphoblastic Leukaemia
University College, London
50 participants
Apr 1, 2016
INTERVENTIONAL
Conditions
Summary
This study aims to evaluate the safety, efficacy and duration of response of CD19+CD22 Chimeric Antigen Receptor (CAR) redirected autologous T-cells in children with high risk, relapsed CD19+ and CD22+ acute lymphoblastic leukaemia
Eligibility
Inclusion Criteria17
- Children and young adults (age 24 years or younger) with high risk/relapsed CD19+ and CD22+ acute lymphoblastic leukaemia with:
- Resistant disease (\>5% blasts) at end of ALLTogether-1 protocol or equivalent induction
- ALL with persisting high level MRD at 2nd time point of frontline national protocol (currently MRD \>10-4 at week 9 ALLTogether-1 Protocol or equivalent).
- High risk infant ALL (age \< 6 months at diagnosis with MLL gene rearrangement and either presenting white cell count \> 300 x 10\^9/L or poor steroid early response (i.e. circulating blast count \>1x10\^9/L following 7 day steroid pre-phase of induction as per national guidelines or equivalent)
- Any patient with t(17,19) TCF3-HLF rearrangement
- High risk 1st relapse (defined as very early (relapse within 18 months of diagnosis) and early relapses (any patient relapsing on therapy or within 6 months of completing treatment) and any relapse with high risk genetics, namely (KMT2A (MLL) rearrangements, low hypodiploidy/near haploidy, t(17;19)(q22;p13)/TCF3-HLF, iAMP21 and t(1;19)(q21;p13)/TCF3- PBX1, t(9;22)(34.1 q11.2)/BCR-ABL1
- Any on therapy relapse in patients age 16-24
- Any relapse of infant ALL
- ALL post ≥ 2nd relapse
- Any refractory relapse of ALL (defined as \> 1% blasts by flow cytometry after a at least 1 cycle of standard chemotherapy)
- ALL with MRD \>10-4 prior to planned stem cell transplant
- Any relapse of ALL eligible for stem cell transplant but no available HLA matched donor or other contraindication to transplant
- Any relapse of ALL after stem cell transplant as long as planned time of CD19+CD22CAR T cell infusion is \> 4 months post-transplant
- Early (defined as \< 6 months post-infusion) loss of B cell aplasia or any CD19+CD22+ relapse following CD19CAR T cell therapy with Tisagenlecleucel
- Note patients with isolated CNS relapse meeting one or more of the criteria above are eligible for the study
- Agreement to have a pregnancy test, use adequate contraception (if applicable)
- Written informed consent
Exclusion Criteria14
- Active Hepatitis B, C or HIV infection
- Oxygen saturation ≤ 90% on air
- Bilirubin \> 3 x upper limit of normal
- Creatinine \> 3 x upper limit of normal
- Women who are pregnant or breastfeeding
- 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.
- Inability to tolerate leucapheresis
- Karnofsky (age ≥ 10 years) or Lansky (age \< 10) score ≤ 50%
- Pre-existing significant neurological disorder (other than CNS involvement of underlying haematological malignancy)
- CD19 negative or CD22 negative disease
- Severe intercurrent infection at the time of scheduled CD19+CD22 CAR T-cell infusion
- Requirement for supplementary oxygen or active pulmonary infiltrates at the time of scheduled CD19+CD22 CAR T-cell infusion
- 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+CD22 CAR T-cell infusion. Note: Such patients will be excluded until the patient is GVHD free and off steroids
- In addition, for CAR T infusion on D14: absence of CRS\>Gr2 or ICANS\>Gr2 after D0 CAR T infusion.
Interventions
Patients will undergo an unstimulated leukapheresis to isolate the required immune cells to produce the CD19+CD22 CAR T-cells
Participants will receive total body irradiation delivered as a single fraction (2Gy) on day -7 prior to CD19+CD22CAR T-cell infusion.
Patients will receive lymphodepleting chemotherapy with iv fludarabine 30 mg/m2 on days -6 to -3 prior to CD19+CD22CAR T-cell infusion.
Patients will receive lymphodepleting chemotherapy with iv cyclophosphamide 0.5 g/m2 on days -6 to -5 prior to CD19+CD22CAR T-cell infusion.
Dose level 1: 2 doses of 4 x 10\^5 CD19+CD22 CAR T-cells/kg Dose level 2: 2 doses of 1 x 10\^6 CD19+CD22 CAR T-cells/kg given as a split dose as an intravenous injection through a Hickman line or PICC line (peripherally inserted central catheter) on day 0 and day 14.
Locations(3)
View Full Details on ClinicalTrials.gov
For the most up-to-date information, visit the official listing.
NCT02443831