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
Rationale
Most adults with B-ALL will die of their disease and adults with refractory or relpased disease have a particularly dismal prognosis. Adults with relapsed or refractory ALL have an overall median survival of about six months. The only potential curative regimen for patients with relapsed ALL is an allogeneic stem cell transplant (SCT). However, only about 25 percent of adults with relapsed ALL receive allogeneic SCT and only 20 percent of these patients have long-term survival of longer than five years. We have developed a novel therapy for B-ALL by genetically targeting patients’ own T cells to CD19, a B cell-specific antigen. CD19 is involved with signal transduction and is a promising therapeutic target since it is expressed on nearly all B cell malignancies. Previously we have shown in mice that CD19-targeted T cells from healthy donors can eradicate systemic B-ALL and Burkitt lymphoma - which makes the infusion of T cells genetically targeted to CD19 a novel and promising therapy for B-ALL.
Patient Population
Adults (>18 years old) with B-ALL in complete remission (CR) or with relapsed or refractory B-ALL are eligible for enrollment. Patients who have received an allogeneic bone marrow transplantation are ineligible for enrollment.
Study Design
This is a phase I dose-escalation trial. The goal of this trial is to assess the safety of autologous gene-modified T cells in B-ALL patients.
Treatment Plan
T cells will be collected in Memorial Sloan-Kettering’s blood donor room and gene targeting will occur in in our Gene Transfer and Somatic Core Facility and in our Center for Cell Engineering. Patients with B-ALL in CR can be enrolled and have their T cells collected but will not be treated on the protocol unless they develop relapsed B-ALL. Patients with relapsed or refractory B-ALL will have their T cells collected and will then be treated with reinduction chemotherapy. The T cells will be genetically targeted to CD19 after reinduction therapy. Once an adequate number of T cells has been generated the patient will be admitted to Memorial Hospital and will receive a single dose of cyclophosphamide and then be injected with their gene-targeted T cells. Infusion of T cells occurs after recovery from reinduction chemotherapy and is not dependent on remission status. Samples of blood and bone marrow will be taken to assess toxicity, therapeutic effects, and survival of the T cells. Progression of disease will remove the patient from the study. All patients can be treated with an allogeneic stem cell transplantation after infusion of gene-targeted T cells if deemed appropriate by a stem cell transplant physician. For more information and to inquire about eligibility for this study, please contact Dr. Renier Brentjens at 212-639-7053.
