Leukemia, Lymphoma
Conditions
Keywords
CAR T cell, CD19, pediatric, young adults
Brief 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.
Interventions
BIOLOGICALSCRI-huCAR19v1
1:1 mixture of CD4:CD8 autologous T cells lentivirally transduced to express a second generation 4-1BB-ζ human CD19-specific CAR and Her2tG
BIOLOGICALSCRI-huCAR19v2
Mixture of CD4:CD8 autologous T cells lentivirally transduced to express a second generation 4-1BB-ζ human CD19-specific CAR and Her2tG
Sponsors
Seattle Children's Hospital
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
1 Years to 30 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The adverse events associated with CAR T cell product infusions will be assessed | 30 days | The type, frequency, severity, and duration of adverse events will be summarized |
| The leukemia response to SCRI-huCAR19 in subjects with relapsed or refractory CD19+ leukemia will be assessed | 63 days | Response will be defined by standard bone marrow assessment and standard response criteria |
Countries
United States
Outcome results
None listed