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

• ClinicalTrials.gov Identifier: NCT03684889
• Recruitment Status: Active, not recruiting
• First Posted: September 26, 2018
• Last Update Posted: April 11, 2022
• Sponsor: Seattle Children's Hospital
• Information provided by (Responsible Party): Rebecca Gardner, Seattle Children's Hospital

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Leukemia; Lymphoma	Biological: SCRI-huCAR19v1; Biological: SCRI-huCAR19v2	Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 16 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: November 28, 2018
• Actual Primary Completion Date: February 8, 2021
• Estimated Study Completion Date: December 2036

Arms and Interventions

Arm	Intervention/treatment
Experimental: SCRI-huCAR19v2; Patients will receive SCRI-huCAR19v2 in either Phase 1 or Phase II	Biological: SCRI-huCAR19v2; Mixture of CD4:CD8 autologous T cells lentivirally transduced to express a second generation 4-1BB-ζ human CD19-specific CAR and Her2tG
Experimental: SCRI-huCAR19v1 - [CLOSED]; Patients will receive SCRI-huCAR19v1 in either Phase 1 or Phase II. As of 02/13/2020 this study cohort is permanently closed.	Biological: SCRI-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

Outcome Measures

Primary Outcome Measures :

1. The adverse events associated with CAR T cell product infusions will be assessed [ Time Frame: 30 days ]
   The type, frequency, severity, and duration of adverse events will be summarized
2. The leukemia response to SCRI-huCAR19 in subjects with relapsed or refractory CD19+ leukemia will be assessed [ Time Frame: 63 days ]
   Response will be defined by standard bone marrow assessment and standard response criteria

Eligibility Criteria

• Ages Eligible for Study: 1 Year to 30 Years (Child, Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

United States, California

Children's Hospital Los Angeles

Los Angeles, California, United States, 90027

United States, Washington

Seattle Children's Hospital

Seattle, Washington, United States, 98105

Sponsors and Collaborators

Seattle Children's Hospital

Investigators

• Study Chair: Colleen Annesley, MD; Seattle Children's Hospital

More Information

• Responsible Party: Rebecca Gardner, Associate Medical Director, Immunotherapy Coordinating Center, Seattle Children's Hospital
• ClinicalTrials.gov Identifier: NCT03684889
• Other Study ID Numbers: PLAT-06
• First Posted: September 26, 2018
• Last Update Posted: April 11, 2022
• Last Verified: April 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Rebecca Gardner, Seattle Children's Hospital:

CAR T cell, CD19, pediatric, young adults

Additional relevant MeSH terms:

Lymphoma; Leukemia; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases