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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02443831
Recruitment Status : Active, not recruiting
First Posted : May 14, 2015
Last Update Posted : May 30, 2024
Sponsor:
Information provided by (Responsible Party):
University College, London

Tracking Information
First Submitted Date  ICMJE April 29, 2015
First Posted Date  ICMJE May 14, 2015
Last Update Posted Date May 30, 2024
Actual Study Start Date  ICMJE April 2016
Estimated Primary Completion Date December 31, 2028   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 16, 2022)
  • Toxicity evaluation following CD19/22CAR T-cell infusion [ Time Frame: 1 month ]
    The incidence of grade 3-5 toxicity occurring within 60 days of CD19/22CAR T-cell infusion. In particular, the incidence of Severe Cytokine Release Syndrome and Grade 3-5 neurotoxicity occurring within 30 days of CD19/22CAR T-cell infusion.
  • Molecular remission [ Time Frame: 1 month ]
    Efficacy will be assessed by determining Minimal Residual Disease in the bone marrow aspirate using immunoglobulin heavy chain (IgH) quantitative polymerase chain reaction (qPCR) and/or Next Generation Sequencing in all patients. The proportion of patients achieving molecular remission at 1 month post CD19/22CAR T-cell infusion will be determined.
Original Primary Outcome Measures  ICMJE
 (submitted: May 13, 2015)
  • Toxicity evaluation following CD19CAR T-cell infusion [ Time Frame: 1 month ]
    The incidence of grade 3-5 toxicity occurring within 30 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.
  • Molecular remission [ Time Frame: 1 month ]
    Efficacy will be assessed by determining Minimal Residual Disease in the bone marrow aspirate using immunoglobulin heavy chain (IgH) quantitative polymerase chain reaction (qPCR) and/or Next Generation Sequencing in all patients. The proportion of patients achieving molecular remission at 1 month post CD19CAR T-cell infusion will be determined.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: May 16, 2022)
  • Long term molecular remission [ Time Frame: 2 years ]
    Number of patients in molecular remission without further therapy at 2 years
  • Frequency of circulating CD19/22 CAR T-cells [ Time Frame: 2 years ]
    Persistence and frequency of circulating CD19/22CAR T-cells in the peripheral blood by flow cytometry and qPCR analyses.
  • Incidence of hypogammaglobulinaemia [ Time Frame: 2 years ]
    Incidence and duration of hypogammaglobulinaemia
  • Relapse rate [ Time Frame: 10 years ]
    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).
  • Overall Survival [ Time Frame: 10 years ]
    Overall survival is monitored during interventional phase and long term follow up for 10 years post-CD19/22 CAR 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).
Original Secondary Outcome Measures  ICMJE
 (submitted: May 13, 2015)
  • Long term molecular remission [ Time Frame: 2 years ]
    Number of patients in molecular remission without further therapy at 2 years
  • Frequency of circulating CD19 CAR T-cells [ Time Frame: 2 years ]
    Persistence and frequency of circulating CD19CAR T-cells in the peripheral blood by flow cytometry and qPCR analyses.
  • Incidence of hypogammaglobulinaemia [ Time Frame: 2 years ]
    Incidence and duration of hypogammaglobulinaemia
  • Relapse rate [ Time Frame: 5 years ]
    Relapse rate monitored during interventional phase and long term follow up for a total of 5 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).
  • Overall Survival [ Time Frame: 5 years ]
    Overall survival is monitored during interventional phase and long term follow up for 5 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).
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE CARPALL: Immunotherapy With CD19/22 CAR T-cells for CD19+ Haematological Malignancies
Official Title  ICMJE Immunotherapy With CD19/22 CAR Redirected T-cells for High Risk, Relapsed Paediatric CD19+ and/or CD22+ Acute Lymphoblastic Leukaemia and Other Haematological Malignancies
Brief Summary This study aims to evaluate the safety, efficacy and duration of response of CD19/22 Chimeric Antigen Receptor (CAR) redirected autologous T-cells in children with high risk, relapsed CD19+ and/ or CD22+ 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 CD19/22 Chimeric Antigen Receptor (CAR) T-cells (CD19/22 CAR T-cells) in children and young adults (age <24 years) with high risk, relapsed CD19+ and/or CD1922+ 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 CD19/22 CAR T-cells. Patients will receive the CD19/22CAR T-cells following lymphodepleting chemotherapy. The study will evaluate the safety, efficacy and duration of response of the CD19/22 CAR T-cells in children with high risk relapsed CD19+ and or CD22+ malignancies.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Acute Lymphoblastic Leukemia
  • Burkitt Lymphoma
Intervention  ICMJE
  • Procedure: Leukapheresis
    Patients will undergo an unstimulated leukapheresis to isolate the required immune cells to produce the CD19/22 CAR T-cells
  • Drug: Lymphodepletion with fludarabine
    Patients will receive lymphodepleting chemotherapy with iv fludarabine 30 mg/m2 on days -7 to -3 prior to CD19/22CAR T-cell infusion.
  • Drug: Lymphodepletion with cyclophosphamide
    Patients will receive lymphodepleting chemotherapy with iv cyclophosphamide 0.5 g/m2 on days -4 to -2 prior to CD19/22CAR T-cell infusion.
  • Biological: CD19/22 CAR T-cells
    A single dose of 1 x 10^6/kg CD19/22CAR transduced T-cells will be given as an intravenous injection through a Hickman line or PICC line(peripherally inserted central catheter) on day 0.
Study Arms  ICMJE Experimental: CD19/22 CAR T-cells
Patients meeting the eligibility criteria will have leukapheresis to isolate the blood immune cells used to manufacture the CD19/22CAR T-cells. Patients will receive lymphodepletion with fludarabine and cyclophosphamide prior to infusion of the CD19/22CAR T-cells.
Interventions:
  • Procedure: Leukapheresis
  • Drug: Lymphodepletion with fludarabine
  • Drug: Lymphodepletion with cyclophosphamide
  • Biological: CD19/22 CAR T-cells
Publications * Ghorashian S, Kramer AM, Onuoha S, Wright G, Bartram J, Richardson R, Albon SJ, Casanovas-Company J, Castro F, Popova B, Villanueva K, Yeung J, Vetharoy W, Guvenel A, Wawrzyniecka PA, Mekkaoui L, Cheung GW, Pinner D, Chu J, Lucchini G, Silva J, Ciocarlie O, Lazareva A, Inglott S, Gilmour KC, Ahsan G, Ferrari M, Manzoor S, Champion K, Brooks T, Lopes A, Hackshaw A, Farzaneh F, Chiesa R, Rao K, Bonney D, Samarasinghe S, Goulden N, Vora A, Veys P, Hough R, Wynn R, Pule MA, Amrolia PJ. Enhanced CAR T cell expansion and prolonged persistence in pediatric patients with ALL treated with a low-affinity CD19 CAR. Nat Med. 2019 Sep;25(9):1408-1414. doi: 10.1038/s41591-019-0549-5. Epub 2019 Sep 2.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: May 29, 2024)
38
Original Estimated Enrollment  ICMJE
 (submitted: May 13, 2015)
18
Estimated Study Completion Date  ICMJE December 31, 2036
Estimated Primary Completion Date December 31, 2028   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE up to 24 Years   (Child, Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United Kingdom
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02443831
Other Study ID Numbers  ICMJE UCL 14/0529
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Current Responsible Party University College, London
Original Responsible Party Same as current
Current Study Sponsor  ICMJE University College, London
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Chair: Persis Amrolia UCL Institute of Child Health
PRS Account University College, London
Verification Date May 2024

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP