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

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Lymphoma; Leukemia
• Intervention / Treatment: Biological: SCRI-huCAR19v2; Biological: SCRI-huCAR19v1

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90027
      • Children's Hospital Los Angeles
  • Washington
    • Seattle, Washington, United States, 98105
      • Seattle Children's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year to 30 years (Child, Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

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

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): November 28, 2018
• Primary Completion (Actual): February 8, 2021
• Study Completion (Estimated): December 1, 2036

Study Registration Dates

• First Submitted: September 17, 2018
• First Submitted That Met QC Criteria: September 24, 2018
• First Posted (Actual): September 26, 2018

Study Record Updates

• Last Update Posted (Actual): June 29, 2023
• Last Update Submitted That Met QC Criteria: June 27, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Keywords: CAR T cell, CD19, pediatric, young adults
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma; Leukemia
• Other Study ID Numbers: PLAT-06

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No