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

Pediatric and Young Adult Leukemia Adoptive Therapy (PLAT)-05: A Phase 1 Feasibility and Safety Study of Dual Specificity CD19 and CD22 CAR-T Cell Immunotherapy for CD19+CD22+ Leukemia

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Lymphoma; Leukemia
• Intervention / Treatment: Biological: Patient-derived CD19- and CD22 specific CAR

• Study Type: Interventional
• Enrollment (Actual): 78
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Colleen Annesley, MD; Phone Number: 206-987-2106; Email: CBDCIntake@seattlechildrens.org

Study Locations

• Canada
  • British Columbia
    • Vancouver, British Columbia, Canada, V6H 3V4
      • Children's and Women's Health Centre of British Columbia
• United States
  • California
    • Los Angeles, California, United States, 90027
      • Children's Hospital Los Angeles
  • District of Columbia
    • Washington, District of Columbia, United States, 20010
      • Children's National Medical Center
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Riley Hospital for Children
  • Washington
    • Seattle, Washington, United States, 98105
      • Seattle Children's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 30 years (Child, Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 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)
• At least 7 das post last systemic corticosteroids administration (unless physiologic replacement dosing)
• No prior genetically modified cell therapy that is still detectable or virotherapy
• Adequate organ function
• Adequate laboratory values
• Willing to participate in long-term follow-up for up to 15 years, if enrolled in the study and receive T cell infusion
• Patients of childbearing/fathering potential must agree to use highly effective contraception from the time of initial T cell infusion through 12 months following the last T cell infusion

Exclusion Criteria:

• 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

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: Patient-derived CD19- and CD22 specific CAR v1; 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-specific CAR also expressing an HER2t and CD22-specific CAR T-cells also expressing an EGFRt
Experimental: Patient-derived CD19- and CD22 specific CAR v2; 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-specific CAR also expressing an HER2t and CD22-specific CAR T-cells also expressing an EGFRt

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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

Collaborators and Investigators

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

Publications and helpful links

General Publications

• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): November 3, 2017
• Primary Completion (Actual): September 13, 2023
• Study Completion (Estimated): March 3, 2035

Study Registration Dates

• First Submitted: October 31, 2017
• First Submitted That Met QC Criteria: November 1, 2017
• First Posted (Actual): November 6, 2017

Study Record Updates

• Last Update Posted (Actual): October 27, 2023
• Last Update Submitted That Met QC Criteria: October 25, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: CD19; CD22; CAR T-cell
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Leukemia
• Other Study ID Numbers: PLAT-05

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
• product manufactured in and exported from the U.S.: No