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)
80
Enrollment
5
Locations
2
Arms
207.9
Anticipated Duration (Months)
16
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 DiseaseIntervention/TreatmentPhase
  • 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

ArmIntervention/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

  1. 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

  2. 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:
No
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

SiteCityStateCountryPostal Code
1Children's Hospital Los AngelesLos AngelesCaliforniaUnited States90027
2Children's National Medical CenterWashingtonDistrict of ColumbiaUnited States20010
3Riley Hospital for ChildrenIndianapolisIndianaUnited States46202
4Seattle Children's HospitalSeattleWashingtonUnited States98105
5Children's and Women's Health Centre of British ColumbiaVancouverBritish ColumbiaCanadaV6H 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:
No
Plan to Share IPD:
No
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by Rebecca Gardner, Associate Medical Director, Immunotherapy Coordinating Center, Seattle Children's Hospital
Additional relevant MeSH terms:

Study Results

No Results Posted as of Apr 5, 2022