cd19-specific car t cells with a fully human binding domain for cd19+ leukemia or lymphoma

Conditions: Leukemia; Lymphoma

Summary: patients with relapsed or refractory leukemia or lymphoma are often refractory to further chemotherapy. in this study, the investigators will attempt to use t cells obtained directly from the patient, which can be genetically engineered to express a fully human chimeric antigen receptor (car). the car used in this study can recognize cd19, a protein expressed on the surface of leukemia and lymphoma cells. the fully human car used in this study may help protect against rejection of the car t cells, which in turn could lead to lasting protection against return of the leukemia or lymphoma. the phase 1 part of this study will determine the safety of these car t cells, and the phase 2 part of the study will determine how effective this car t cell therapy is. both patients who have never had prior car t cell therapy and those who have had prior car t cell therapy may be eligible to participate in this study.


Eligibility criteria:
inclusion criteria: * male and female subjects age ≥ 1 and ≤ 30 years * first 2 enrolled subjects: age ≥ 18 and ≤ 30 years * disease requirements: * phase 1: evidence of refractory or recurrent cd19+ leukemia or lymphoma following previous car t cell immunotherapy * phase 2: evidence of refractory or recurrent cd19+ leukemia or lymphoma * able to tolerate apheresis, or has sufficient existing apheresis product or t cells for manufacturing investigational product * life expectancy ≥ 8 weeks * lansky or karnofsky, as applicable, score ≥ 50 * recovered from acute toxic effects of all prior chemotherapy, immunotherapy, and radiotherapy, if the subject does not have a previously obtained apheresis product that is acceptable and available for manufacturing of car t cells * ≥ 7 days post last chemotherapy and biologic therapy, with the exception of intrathecal chemotherapy and maintenance chemotherapy * no prior virotherapy * ≥ 7 days post last corticosteroid therapy * ≥ 3 days post tyrosine kinase inhibitor (tki) use * ≥ 1 day post hydroxyurea * 30 days post most recent car t cell infusion * adequate organ function * adequate laboratory values, including absolute lymphocyte count ≥ 100 cells/ul * subjects of childbearing or child-fathering potential must agree to use highly effective contraception from consent through 12 months following infusion of investigational product on trial * subject and/or legally authorized representative has signed the informed consent form for this study exclusion criteria: * presence of active malignancy other than disease under study * history of symptomatic cns pathology or ongoing symptomatic cns pathology * cns involvement of leukemia or lymphoma that is symptomatic and in the opinion of the investigator, cannot be controlled during the interval between enrollment and car t cell infusion * presence of active gvhd, or receiving immunosuppressive therapy for treatment or prevention of gvhd within 4 weeks prior to enrollment * presence of active severe infection * presence of primary immunodeficiency syndrome * subject has received prior virotherapy * pregnant or breastfeeding * subject and/or legally authorized representative unwilling to provide consent/assent for participation in the 15-year follow up period, required if car t cell therapy is administered * presence of any condition that, in the opinion of the investigator, would prohibit the patient from undergoing treatment under this protocol

Keywords: car t cell, cd19, pediatric, young adults