Clinical trial NCT03244306: A Phase 1 Study of CD22-CAR TCell Immunotherapy for CD22+ Leukemia and Lymphoma
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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
Conditions: Leukemia
Keywords: leukemia
CD 22
CAR T cell
pediatric
young adult
chimeric antigen receptor
Lead sponsor: Seattle Children's Hospital
Sponsor class: OTHER
First posted: 2017-08-09
Enrollment: 4
Sex: ALL
Minimum age (years): 1
Maximum age (years): 26
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: 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):

  1. If post-allogeneic hematopoetic cell transplant (HCT): confirmed CD22+ leukemia recurrence, defined as ≥0.01% disease
  2. 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
  3. 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

Primary outcomes:
measure: The adverse events associated with one or multiple CAR T-cell product infusions will be assessed
timeFrame: 30 days
measure: The number of successfully and unsuccessfully manufactured and infused CAR T-cell products will be assessed
timeFrame: 28 days
Secondary outcomes:
Other outcomes:
Locations:
city: Seattle
country: United States
facility: Seattle Children's Hospital
state: Washington
Study officials:
affiliation: Seattle Children's Hospital
name: Corinne Summers, MD
role: STUDY_CHAIR
References: