Clinical Trials /

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

NCT02443831

Description:

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.

Related Conditions:
  • Acute Lymphoblastic Leukemia
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: CARPALL: Immunotherapy With CD19 CAR T-cells for CD19+ Haematological Malignancies
  • Official Title: Immunotherapy With CD19 CAR Redirected T-cells for High Risk, Relapsed Paediatric CD19+ Acute Lymphoblastic Leukaemia and Other Haematological Malignancies

Clinical Trial IDs

  • ORG STUDY ID: UCL 14/0529
  • NCT ID: NCT02443831

Conditions

  • Acute Lymphoblastic Leukemia
  • Burkitt Lymphoma

Interventions

DrugSynonymsArms
Lymphodepletion with fludarabineCD19 CAR T-cells
Lymphodepletion with cyclophosphamideCD19 CAR T-cells
CD19 CAR T-cellsCD19 CAR T-cells

Purpose

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.

Detailed Description

      This is a multi-centre, non-randomised, open label Phase I clinical trial of an Advanced
      Therapy Investigational Medicinal Product named CD19 Chimeric Antigen Receptor (CAR) T-cells
      (CD19 CAR T-cells) in children and young adults (age <24 years) with high risk, relapsed
      CD19+ haematological malignancies (Acute Lymphoblastic Leukemia and Burkitt's lymphoma).
      Following informed consent and registration to the trial, patients will undergo an
      unstimulated leukapheresis for the generation of the CD19 CAR T-cells. Patients will receive
      the CD19CAR T-cells following lymphodepleting chemotherapy. The study will evaluate the
      safety, efficacy and duration of response of the CD19 CAR T-cells in children with high risk
      relapsed CD19+ malignancies.
    

Trial Arms

NameTypeDescriptionInterventions
CD19 CAR T-cellsExperimentalPatients meeting the eligibility criteria will have leukapheresis to isolate the blood immune cells used to manufacture the CD19CAR T-cells. Patients will receive lymphodepletion with fludarabine and cyclophosphamide prior to infusion of the CD19CAR T-cells.
  • Lymphodepletion with fludarabine
  • Lymphodepletion with cyclophosphamide
  • CD19 CAR T-cells

Eligibility 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
      
Maximum Eligible Age:24 Years
Minimum Eligible Age:N/A
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Toxicity evaluation following CD19CAR T-cell infusion
Time Frame:1 month
Safety Issue:
Description:The incidence of grade 3-5 toxicity occurring within 60 days of CD19CAR T-cell infusion. In particular, the incidence of Severe Cytokine Release Syndrome and Grade 3-5 neurotoxicity occurring within 30 days of CD19CAR T-cell infusion.

Secondary Outcome Measures

Measure:Long term molecular remission
Time Frame:2 years
Safety Issue:
Description:Number of patients in molecular remission without further therapy at 2 years
Measure:Frequency of circulating CD19 CAR T-cells
Time Frame:2 years
Safety Issue:
Description:Persistence and frequency of circulating CD19CAR T-cells in the peripheral blood by flow cytometry and qPCR analyses.
Measure:Incidence of hypogammaglobulinaemia
Time Frame:2 years
Safety Issue:
Description:Incidence and duration of hypogammaglobulinaemia
Measure:Relapse rate
Time Frame:10 years
Safety Issue:
Description:Relapse rate monitored during interventional phase and long term follow up for a total of10 years post cell infusion. Number of patients who relapsed can be summarized as a percentage or rate(for all patients registered to the trial, and also only for those who received the cell infusion).
Measure:Overall Survival
Time Frame:10 years
Safety Issue:
Description:Overall survival is monitored during interventional phase and long term follow up for 10 years post-CD19CAR T-cell infusion. Number of patients alive can be summarized as a percentage (for all patients registered to the trial, and also only for those who received the cell infusion).

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:University College, London

Trial Keywords

  • high risk relapsed CD19+ hematological malignancies

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