Clinical Trials /

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

NCT03330691

Description:

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.

Related Conditions:
  • Leukemia
  • Lymphoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • 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

Clinical Trial IDs

  • ORG STUDY ID: PLAT-05
  • NCT ID: NCT03330691

Conditions

  • Leukemia
  • Lymphoma

Interventions

DrugSynonymsArms
Patient-derived CD19- and CD22 specific CARPatient-derived CD19- and CD22 specific CAR

Purpose

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.

Trial Arms

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

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: male and female
             subjects age ≥12 months of age and <27 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
      
Maximum Eligible Age:26 Years
Minimum Eligible Age:12 Months
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:The adverse events associated with one or multiple CAR T-cell product infusions will be assessed
Time Frame:30 days
Safety Issue:
Description:Type, frequency, severity, and duration of adverse events will be summarized

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Seattle Children's Hospital

Trial Keywords

  • CD19
  • CD22
  • CAR T-cell

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