Precursor B Cell Acute Lymphoblastic Leukemia (B-ALL) Treated With Autologous T Cells Genetically Targeted to the B Cell Specific Antigen CD19
This study is an investigational approach that uses immune cells, called "T cells", to kill leukemia. These T cells are removed from blood, modified in a laboratory, and then put back in the body. T cells fight infections and can also kill cancer cells in some cases. However, right now T cells are unable to kill the cancer cells. For this reason we will put one gene into the T cells that allows them to recognize and kill the leukemia cells. This gene will be put in the T cells by a weakened virus. The gene will produce proteins in the T cells that help the T cells recognize the leukemia cells and possibly kill them. The doctors have found that T cells modified in this way can cure an ALL-like cancer in mice.
The main goals of this study is to determine the safety and appropriate dose of these modified T cells in patients with ALL. This will be done in a "clinical trial." The dose of modified T-cells will depend on if you have disease present in your bone marrow or not. The patient will also receive chemotherapy before the T cells. We will use normally chemotherapy that is used in patients with leukemia. The chemotherapy is given to reduce leukemia and to allow the T cells to live longer.
Acute Lymphoblastic Leukemia
Biological: gene-modified T cells targeted
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase I Trial of Precursor B Cell Acute Lymphoblastic Leukemia (B-ALL) Treated With Autologous T Cells Genetically Targeted to the B Cell Specific Antigen CD19|
- To evaluate the safety of adoptive transfer of gene-modified autologous CD19-specific T cells in adult patients with B-ALL. [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
- To assess the anti-leukemic effect of adoptively transferred anti-CD19 T cells. [ Time Frame: 2 years ] [ Designated as safety issue: No ]
|Study Start Date:||January 2010|
|Estimated Study Completion Date:||January 2016|
|Estimated Primary Completion Date:||January 2016 (Final data collection date for primary outcome measure)|
Experimental: Pts with B Cell Acute Lymphoblastic Leukemia
This is a phase I study. Patients with CD19+ ALL (CR, relapsed, MRD, or refractory) are eligible for enrollment. B-ALL patients in first CR will be enrolled but only treated if they develop MRD or a frank relapse, while patients with MRD or with documented relapsed/refractory disease are eligible for immediate treatment. The T cell doses originally proposed in this study were based on doses administered safely in prior autologous T cell adoptive therapy trials but the dose has been modified based on the toxicities observed in patients with morphologic evidence of disease. Patients will be treated with different doses of T cells depending on the amount of disease at the time of T cell infusion. Patients in Cohort 1 (<5% blasts in the BM) will continue to receive 10^6 19-28z+ T cells/kg as previously. Patients in Cohort 2 (≥5% blasts in the BM) will receive the reduced dose of 1x106 19-28z+ T cells/kg).
Biological: gene-modified T cells targeted
Pts will undergo leukapheresis. The leukapheresis product will be washed & frozen until the GTF is directed to start T cell production by the PI. CD3+ T cells will be isolated from the leukapheresis, & transduced with the 19-28z chimeric receptor & expanded. All relapsed (either MRD+ or morphologic) & refractory pts get re-induction chemo whenever feasible to optimally reduce the tumor burden prior to the T cell infusion. The re-induction chemo regimen will be selected by the treating dr. based on prior therapy, adverse reactions to chemo & highest likelihood to achieve an optimal response. Once pts recover from the toxicities of the re-induction chemo the disease status will be re-evaluated by repeating bone marrow aspirate or biopsy. Pts get conditioning chemo (min 2 weeks from end of re-induction chemo) followed 2-7 days later by the 19-28z+ T cells. Pts will be tx in 2 cohorts with diff doses of T cells according to the amount of disease immediately prior to the T cell infusion.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01044069
|Contact: Jae Park, MD||212-639-4048|
|Contact: Dan Douer, MD||212-639-2471|
|United States, New York|
|Memorial Sloan Kettering Cancer Center||Recruiting|
|New York, New York, United States, 10065|
|Contact: Jae Park, MD 212-639-4048|
|Principal Investigator: Jae Park, MD|
|Principal Investigator:||Jae Park, MD||Memorial Sloan Kettering Cancer Center.|