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CD19-specific CAR T Cells With a Fully Human Binding Domain for CD19+ Leukemia or Lymphoma

Phase 1
Active, not recruiting
Conditions
Leukemia
Lymphoma
Interventions
Biological: SCRI-huCAR19v2
Biological: SCRI-huCAR19v1
Registration Number
NCT03684889
Lead Sponsor
Seattle Children's Hospital
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.

Detailed Description

Not available

Recruitment & Eligibility

Status
ACTIVE_NOT_RECRUITING
Sex
All
Target Recruitment
16
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
SCRI-huCAR19v2SCRI-huCAR19v2Patients will receive SCRI-huCAR19v2 in either Phase 1 or Phase II
SCRI-huCAR19v1 - [CLOSED]SCRI-huCAR19v1Patients will receive SCRI-huCAR19v1 in either Phase 1 or Phase II. As of 02/13/2020 this study cohort is permanently closed.
Primary Outcome Measures
NameTimeMethod
The adverse events associated with CAR T cell product infusions will be assessed30 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 assessed63 days

Response will be defined by standard bone marrow assessment and standard response criteria

Secondary Outcome Measures
NameTimeMethod

Trial Locations

Locations (2)

Children's Hospital Los Angeles

🇺🇸

Los Angeles, California, United States

Seattle Children's Hospital

🇺🇸

Seattle, Washington, United States

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