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

Primary Purpose

Leukemia, Lymphoma

Status
Recruiting
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
Patient-derived CD19- and CD22 specific CAR
Sponsored by
Seattle Children's Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Leukemia focused on measuring CD19, CD22, CAR T-cell

Eligibility Criteria

undefined - 30 Years (Child, Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Children's Hospital Los AngelesRecruiting
  • Children's National Medical CenterRecruiting
  • Riley Hospital for ChildrenRecruiting
  • Seattle Children's HospitalRecruiting
  • Children's and Women's Health Centre of British ColumbiaRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Patient-derived CD19- and CD22 specific CAR v1

Patient-derived CD19- and CD22 specific CAR v2

Arm Description

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

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

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

Full Information

First Posted
October 31, 2017
Last Updated
June 27, 2023
Sponsor
Seattle Children's Hospital
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1. Study Identification

Unique Protocol Identification Number
NCT03330691
Brief Title
A Feasibility and Safety Study of Dual Specificity CD19 and CD22 CAR-T Cell Immunotherapy for CD19+CD22+ Leukemia
Official Title
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
Study Type
Interventional

2. Study Status

Record Verification Date
June 2023
Overall Recruitment Status
Recruiting
Study Start Date
November 3, 2017 (Actual)
Primary Completion Date
September 15, 2023 (Anticipated)
Study Completion Date
March 3, 2035 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Seattle Children's Hospital

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Leukemia, Lymphoma
Keywords
CD19, CD22, CAR T-cell

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
80 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Patient-derived CD19- and CD22 specific CAR v1
Arm Type
Experimental
Arm Description
Patient-derived CD19-specific CAR also expressing an HER2t and CD22-specific CAR T-cells also expressing an EGFRt
Arm Title
Patient-derived CD19- and CD22 specific CAR v2
Arm Type
Experimental
Arm Description
Patient-derived CD19-specific CAR also expressing an HER2t and CD22-specific CAR T-cells also expressing an EGFRt
Intervention Type
Biological
Intervention Name(s)
Patient-derived CD19- and CD22 specific CAR
Intervention Description
Patient-derived CD19-specific CAR also expressing an HER2t and CD22-specific CAR T-cells also expressing an EGFRt
Primary Outcome Measure Information:
Title
The adverse events associated with one or multiple CAR T-cell product infusions will be assessed
Description
Type, frequency, severity, and duration of adverse events will be summarized
Time Frame
30 days
Title
The number of successfully and unsuccessfully manufactured and infused CAR T-cell products will be assessed
Description
Proportion of products successfully manufactured and infused
Time Frame
28 days

10. Eligibility

Sex
All
Maximum Age & Unit of Time
30 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Colleen Annesley, MD
Phone
206-987-2106
Email
CBDCIntake@seattlechildrens.org
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Colleen Annesley, MD
Organizational Affiliation
Seattle Children's Hospital
Official's Role
Study Chair
Facility Information:
Facility Name
Children's Hospital Los Angeles
City
Los Angeles
State/Province
California
ZIP/Postal Code
90027
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Lee Chen
First Name & Middle Initial & Last Name & Degree
Emily Hsieh, MD
Facility Name
Children's National Medical Center
City
Washington
State/Province
District of Columbia
ZIP/Postal Code
20010
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Anant Vatsayan, MD
Email
avatsayan@childrensnational.org
First Name & Middle Initial & Last Name & Degree
Emily Miller
Email
ejmiller@childrensnational.org
First Name & Middle Initial & Last Name & Degree
Anant Vatsayan, MD
Facility Name
Riley Hospital for Children
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46202
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jodi Skiles, MD
First Name & Middle Initial & Last Name & Degree
Jodi Skiles, MD
Facility Name
Seattle Children's Hospital
City
Seattle
State/Province
Washington
ZIP/Postal Code
98105
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Colleen Annesley, MD
Phone
206-987-2106
Email
CBDCIntake@seattlechildrens.org
First Name & Middle Initial & Last Name & Degree
Rebecca Gardner, MD
Facility Name
Children's and Women's Health Centre of British Columbia
City
Vancouver
State/Province
British Columbia
ZIP/Postal Code
V6H 3V4
Country
Canada
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Kirk Schultz, MD
Phone
604-875-2416
Email
kschultz@mail.ubc.ca
First Name & Middle Initial & Last Name & Degree
Amanda Li, MD
Phone
604-875-2316
Email
ali3@cw.bc.ca

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
34889384
Citation
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.
Results Reference
derived
PubMed Identifier
34244298
Citation
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.
Results Reference
derived

Learn more about this trial

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

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