CARPALL: Immunotherapy With CD19/22 CAR T-cells for CD19+ Haematological Malignancies
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|ClinicalTrials.gov Identifier: NCT02443831|
Recruitment Status : Active, not recruiting
First Posted : May 14, 2015
Last Update Posted : July 21, 2022
|Condition or disease||Intervention/treatment||Phase|
|Acute Lymphoblastic Leukemia Burkitt Lymphoma||Procedure: Leukapheresis Drug: Lymphodepletion with fludarabine Drug: Lymphodepletion with cyclophosphamide Biological: CD19/22 CAR T-cells||Phase 1|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||33 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Immunotherapy With CD19/22 CAR Redirected T-cells for High Risk, Relapsed Paediatric CD19+ and/or CD22+ Acute Lymphoblastic Leukaemia and Other Haematological Malignancies|
|Actual Study Start Date :||April 2016|
|Estimated Primary Completion Date :||January 2, 2024|
|Estimated Study Completion Date :||January 2032|
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.
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.
- 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.
- 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).
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02443831
|Great Ormond Street Hospital|
|London, United Kingdom|
|University College Hospital|
|London, United Kingdom|
|Manchester Royal Children's Hospital|
|Manchester, United Kingdom|
|Study Chair:||Persis Amrolia||UCL Institute of Child Health|