Clinical trial NCT03684889: CD19-specific CAR T Cells With a Fully Human Binding Domain for CD19+ Leukemia or Lymphoma
Official title: Pediatric and Young Adult Leukemia Adoptive Therapy (PLAT)-06: A Phase 1/2 Study of CD19-specific CAR T Cells With a Fully Human Binding Domain for CD19+ Leukemia or Lymphoma
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
Conditions: Leukemia
Lymphoma
Keywords: CAR T cell, CD19, pediatric, young adults
Lead sponsor: Seattle Children's Hospital
Sponsor class: OTHER
First posted: 2018-09-26
Enrollment: 16
Sex: ALL
Minimum age (years): 1
Maximum age (years): 30
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: The adverse events associated with CAR T cell product infusions will be assessed
timeFrame: 30 days
measure: The leukemia response to SCRI-huCAR19 in subjects with relapsed or refractory CD19+ leukemia will be assessed
timeFrame: 63 days
Secondary outcomes:
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Children's Hospital Los Angeles
state: California
city: Seattle
country: United States
facility: Seattle Children's Hospital
state: Washington
Study officials:
affiliation: Seattle Children's Hospital
name: Colleen Annesley, MD
role: STUDY_CHAIR
References: