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

Sponsor

Seattle Children's Hospital (Other)

Overall Status

Recruiting

CT.gov ID

NCT03330691

Collaborator

(none)

Enrollment

Locations

Arms

207.9

Anticipated Duration (Months)

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Leukemia Lymphoma	Biological: Patient-derived CD19- and CD22 specific CAR	Phase 1

Study Design

Study Type:

Interventional

Anticipated Enrollment :

80 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)-05: A Phase 1 Feasibility and Safety Study of Dual Specificity CD19 and CD22 CAR-T Cell Immunotherapy for CD19+CD22+ Leukemia

Actual Study Start Date :

Nov 3, 2017

Anticipated Primary Completion Date :

Dec 15, 2022

Anticipated Study Completion Date :

Mar 3, 2035

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

The adverse events associated with one or multiple CAR T-cell product infusions will be assessed [30 days]
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 [28 days]
Proportion of products successfully manufactured and infused

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A to 30 Years

Sexes Eligible for Study:

All

Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Children's Hospital Los Angeles	Los Angeles	California	United States	90027
2	Children's National Medical Center	Washington	District of Columbia	United States	20010
3	Riley Hospital for Children	Indianapolis	Indiana	United States	46202
4	Seattle Children's Hospital	Seattle	Washington	United States	98105
5	Children's and Women's Health Centre of British Columbia	Vancouver	British Columbia	Canada	V6H 3V4

Sponsors and Collaborators

Seattle Children's Hospital

Investigators

Study Chair: Rebecca Gardner, MD, Seattle Children's Hospital

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Rebecca Gardner, Associate Medical Director, Immunotherapy Coordinating Center, Seattle Children's Hospital

ClinicalTrials.gov Identifier:

NCT03330691

Other Study ID Numbers:

PLAT-05

First Posted:

Nov 6, 2017

Last Update Posted:

Apr 5, 2022

Last Verified:

Apr 1, 2022

Individual Participant Data (IPD) Sharing Statement:

Plan to Share IPD:

Studies a U.S. FDA-regulated Drug Product:

Yes

Studies a U.S. FDA-regulated Device Product:

Keywords provided by Rebecca Gardner, Associate Medical Director, Immunotherapy Coordinating Center, Seattle Children's Hospital

CD19

CD22

CAR T-cell

Additional relevant MeSH terms:

Leukemia

Study Results

No Results Posted as of Apr 5, 2022