PLAT-04: A Phase 1 Study of CD22-CAR TCell Immunotherapy for CD22+ Leukemia and Lymphoma

Sponsor

Seattle Children's Hospital (Other)

Overall Status

Active, not recruiting

CT.gov ID

NCT03244306

Collaborator

(none)

Enrollment

Location

Arm

215.1

Anticipated Duration (Months)

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 a chimeric antigen receptor (CAR) to CD22, a different protein from CD19, expressed on the surface of the leukemic cell in patients with CD22+ leukemia. The CAR enables the T-cell to recognize and kill the leukemic cell through the recognition of CD22, a protein expressed on the surface of the leukemic cell in patients with CD22+ leukemia. This is a Phase 1 study designed to determine the safety and feasibility of the CAR+ T - cells and the feasibility of making enough to treat patients with CD22+ leukemia.

Condition or Disease	Intervention/Treatment	Phase
Leukemia	Biological: Patient-derived CD22-specific CAR T-cells also expressing an EGFRt	Phase 1

Study Design

Study Type:

Interventional

Actual Enrollment :

4 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Pediatric and Young Adult Leukemia Adoptive Therapy (PLAT)-04: A Phase 1 Feasibility and Safety Study of CD22-CAR T Cell Immunotherapy for CD22+ Leukemia and Lymphoma

Actual Study Start Date :

Jul 27, 2017

Actual Primary Completion Date :

Nov 14, 2018

Anticipated Study Completion Date :

Jul 1, 2035

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Autologous CD22-specific CAR T-cells expressing EGFRt	Biological: Patient-derived CD22-specific CAR T-cells also expressing an EGFRt Patient-derived CD22-specific chimeric antigen receptor T-cells expressing an EGFRt

Arm

Intervention/Treatment

Experimental: Autologous CD22-specific CAR T-cells expressing EGFRt

Biological: Patient-derived CD22-specific CAR T-cells also expressing an EGFRt

Patient-derived CD22-specific chimeric antigen receptor T-cells 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]
The 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:

1 Year to 26 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

First 3 subjects: male and female subjects age ≥ 18 years and < 27 years
Subsequent subjects: 12 months of age and <27 years of age at the time of study enrollment
Disease status (one of the following):

If post-allogeneic hematopoetic cell transplant (HCT): confirmed CD22+ leukemia recurrence, defined as ≥0.01% disease
If Relapse/Refractory status with no prior history of allogeneic HCT, one of:

2nd or grater marrow relapse, with or without extramedullary disease
1st marrow relapse at end of 1st month of re-induction with marrow having ≥0.01% blasts by morphology and/or MPF
Primary Refractory, defined as >5% blasts by multi-parameter flow after ≥2 separate induction regimens
Subject has indication for HCT but is ineligible, inclusive of persistent minimal residual disease

CD22+ Lymphoma refractory or relapsed with no known curative therapies available

Asymptomatic from CNS involvement, if present, and have 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.
Lansky or Karnofsky performance score of ≥50
Life expectancy of >8 weeks
Recovered from acute toxic effects of all prior chemotherapy, immunotherapy, and radiotherapy
≥7 days post last chemotherapy administration (excluding intrathecal or maintenance chemotherapy)
≥7 days post last systemic corticosteroid administration
No prior virotherapy
Adequate organ function
Adequate laboratory values
Patients of childbearing/fathering potential must agree to use highly effective contraception
Signed a written consent

Exclusion Criteria:

Presence of active clinically significant CNS dysfunction
Pregnant or breastfeeding
Unable to tolerate apheresis procedure, including placement of temporary apheresis line if required
Presence of active malignancy other than CD22+ leukemia or lymphoma
Presence of active severe infection
Presence of any concurrent medical condition that would prevent the patient from undergoing protocol-based therapy
Presence of primary immunodeficiency/bone marrow failure syndrome
Unwilling to participate in 15-year follow-up period that is required if CAR T cell therapy is administered