A Feasibility and Safety Study of Dual Specificity CD19 and CD22 CAR-T Cell Immunotherapy for CD19+CD22+ Leukemia

NCT03330691 | Active Not Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: PLAT-05
• Study Type: interventional
• Target: 78
• Locations: 2 countries
• Sites: 5

Brief Summary

Patients with relapsed or refractory leukemia often develop resistance to chemotherapy and some patients who relapse following CD19 directed therapy relapse with CD19 negative leukemia. For this reason, the investigators are attempting to use T-cells obtained directly from the patient, which can be genetically modified to express two chimeric antigen receptors (CARs). One is to recognize CD19 and the other is to recognize CD22, both of which are proteins expressed on the surface of the leukemic cell in patients with CD19+CD22+ leukemia. The CAR enables the T-cell to recognize and kill the leukemic cell through recognition of CD19 and CD22. This is a phase 1 study designed to determine the safety of the CAR+ T-cells and the feasibility of making enough to treat patients with CD19+CD22+ leukemia.

Conditions

Leukemia; Lymphoma

Keywords

CD19; CD22; CAR T-cell

Outcome Measures

Primary Outcomes (2)

• The adverse events associated with one or multiple CAR T-cell product infusions will be assessed

  Type, frequency, severity, and duration of adverse events will be summarized

  30 days

• The number of successfully and unsuccessfully manufactured and infused CAR T-cell products will be assessed

  Proportion of products successfully manufactured and infused

  28 days

Study Arms (2)

Patient-derived CD19- and CD22 specific CAR v1

EXPERIMENTAL

Patient-derived CD19-specific CAR also expressing an HER2t and CD22-specific CAR T-cells also expressing an EGFRt

Biological: Patient-derived CD19- and CD22 specific CAR

Patient-derived CD19- and CD22 specific CAR v2

EXPERIMENTAL

Patient-derived CD19-specific CAR also expressing an HER2t and CD22-specific CAR T-cells also expressing an EGFRt

Biological: Patient-derived CD19- and CD22 specific CAR

Interventions

Patient-derived CD19- and CD22 specific CAR BIOLOGICAL

Patient-derived CD19-specific CAR also expressing an HER2t and CD22-specific CAR T-cells also expressing an EGFRt

Patient-derived CD19- and CD22 specific CAR v1; Patient-derived CD19- and CD22 specific CAR v2

Eligibility Criteria

• Age: Up to 30 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• First 2 subjects: male and female subjects age ≥18 and \< 27 years (as of 2/16/18 the first 2 subjects were enrolled and treated); subsequent subjects \<31 years.
• Diagnosis of CD19+22+ leukemia
• Disease status:
• If post allogeneic HCT: Confirmed CD19+CD22+ leukemia recurrence defined as at least 0.01% disease following allogeneic HCT
• If relapse/refractory status with no prior history of allogeneic HCT, one of the following:
• Second or greater marrow relapse, with or without extramedullary disease
• First marrow relapse at end of first month or re-induction with marrow having at least 0.01 % blasts by morphology and/or MPF
• Primary refractory as defined as greater than 5% blasts by multi-parameter flow after at least 2 separate induction regimens.
• Subject has indication for HCT but has been deemed ineligible, inclusive of persistent MRD prior to HCT
• Asymptomatic from CNS involvement, if present, and in the opinion of the Principal Investigator with a reasonable expectation that disease burden can be controlled in the interval between enrollment and T-cell infusion. Subjects with significant neurologic deterioration will not be eligible for T-cell infusion until stabilized.
• Free from active GVHD and off immunosuppressive GVHD therapy for 4 weeks prior to enrollment
• Lansky or Karnofsky performance score of at least 50
• Life expectancy of at least 8 weeks
• Recovered from acute toxic effects of all prior chemotherapy, immunotherapy, and radiotherapy
• At least 7 days post last chemotherapy administration (excluding intrathecal maintenance chemotherapy)

You may not qualify if:

• Presence of active clinically significant CNS dysfunction
• Pregnant or breast-feeding
• Unable to tolerate apheresis procedure
• Presence of active malignancy other than CD19+CD22+ leukemia
• Presence of active severe infection
• Presence of any concurrent medical condition that, in the opinion of the Principal Investigator, would prevent the patient from undergoing protocol-specified therapy

Sponsors & Collaborators

• Seattle Children's Hospital: lead

Study Sites (5)

Children's Hospital Los Angeles

Los Angeles, California, 90027, United States

Location

Children's National Medical Center

Washington D.C., District of Columbia, 20010, United States

Location

Riley Hospital for Children

Indianapolis, Indiana, 46202, United States

Location

Seattle Children's Hospital

Seattle, Washington, 98105, United States

Location

Children's and Women's Health Centre of British Columbia

Vancouver, British Columbia, V6H 3V4, Canada

Location

Related Publications (2)

• Singh N. Modified T cells as therapeutic agents. Hematology Am Soc Hematol Educ Program. 2021 Dec 10;2021(1):296-302. doi: 10.1182/hematology.2021000262.

  PMID: 34889384 DERIVED

• Johnson AJ, Wei J, Rosser JM, Kunkele A, Chang CA, Reid AN, Jensen MC. Rationally Designed Transgene-Encoded Cell-Surface Polypeptide Tag for Multiplexed Programming of CAR T-cell Synthetic Outputs. Cancer Immunol Res. 2021 Sep;9(9):1047-1060. doi: 10.1158/2326-6066.CIR-20-0470. Epub 2021 Jul 9.

  PMID: 34244298 DERIVED

MeSH Terms

Conditions

Leukemia; Lymphoma

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• Colleen Annesley, MD

  Seattle Children's Hospital

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Medical Director, Seattle Children's Therapeutics

Study Record Dates

• First Submitted: October 31, 2017
• First Posted: November 6, 2017
• Study Start: November 3, 2017
• Primary Completion: September 13, 2023
• Study Completion (Estimated): March 3, 2035
• Last Updated: December 15, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (4); CA (1)