A Pediatric and Young Adult Trial of Genetically Modified T Cells Directed Against CD19 for Relapsed/Refractory CD19+ Leukemia
CD19+ Acute Leukemia
Conditions: official terms
Conditions: Keywords
pediatric, young adult, acute lymphoblastic leukemia, CD19, leukemia, Chimeric Antigen Receptor, T cell
Study Type
Study Phase
Phase 1/Phase 2
Study Design
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Name: Patient Derived CD19 specific CAR T cells also expressing an EGFRt
Type: Biological
Overall Status
Patients with relapsed or refractory leukemia often develop resistance to chemotherapy. For this reason, we are attempting to use T cells obtained directly from the patient, which can be genetically modified to express a chimeric antigen receptor (CAR). The CAR enables the T cell to recognize and kill the leukemic cell through the recognition of CD19, a protein expressed of the surface of the leukemic cell in patients with CD19+ leukemia. This is a phase 1/2 study designed to determine the maximum tolerated dose of the CAR+ T cells as well as to determine the efficacy. The phase 1 cohort is restricted to those patients who have already had an allogeneic hematopoietic cell transplant (HCT). The phase 2 is open to all patients regardless of having a history of HCT.
Detailed Description
Upon meeting the eligibility requirements and enrolling on study, subjects will undergo apheresis to obtain the T cells for the generation of the CD19 CAR+ T cells. In patients with a prior history of allogeneic HCT, the T cells obtained are of donor origin. The T cells are isolated from the apheresis product, the CD4 and CD8 T cells are then selected and grown separately, transduced with a lentivirus to express the CD19 CAR as well as a truncated EGFR that has no signaling capacity (noted EGFRt) and expanded in culture over a three week period. During the process of cell generation, subjects will continue to be cared for by their primary oncologist and may undergo additional treatment directed at the leukemia during this time.

After the CAR+ T cells have been generated, the subject undergoes a disease assessment and determination if lymphodepletion is necessary. A variety of lymphodepletion strategies are acceptable and determined on a case by case basis. At least 48 hours after the completion of lymphodepletion, the subject will receive and infusion of CAR+ T cells at an approximate 1:1 ratio of CD4 to CD8 CAR+ T cells.

Following treatment with the CAR+ T cells, subjects will be followed intensely for 2 months with serial blood testing and re-evaluation of disease status with bone marrow aspirates. After 2 months, the subjects clinical care will be resumed by their primary oncologist, and it is possible that they would receive additional chemotherapy or HCT.

Some subjects will receive cetuximab for ablation of the genetically modified T cells. Criteria to receive cetuximab include acute toxicities that are life threatening, as well as an ongoing remission with continued B cell aplasia.

Upon completion of the study, subjects will be followed bi-annually for 5 years, and then annually for 10 additional years with either a medical history, physical exam and blood tests or a phone call/questionnaire. This follow up will help to determine if the subject develops any long-term health problems related to the CAR+ T cells including a new cancer.
Criteria for eligibility
Healthy Volunteers: No
Maximum Age: 26 Years
Minimum Age: 1 Year
Gender: Both
Criteria: Inclusion Criteria:

- Must be >/= 10kg

- Clinical diagnosis CD19+ leukemia that meets one of the following:

1. CD19+ leukemia recurrence after allo-HCT defined as >/= 0.01% disease

2. 2nd or greater marrow relapse

3. 1st marrow relapse at end of 1st month of re-induction with marrow having >/= 0.01% blasts by morphology and /or multiparameter flow

4. primary refractory as defined as having M2 or M3 marrow after 2 or more separate induction regimens

5. subject has indication for HCT but has been deemed ineligible

- Karnofsky or lansky of >/= 50

- Life Expectancy of > 8 weeks

- Recovered from acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy

1. must be at least 7 days since last chemotherapy was administered (this does not include intrathecal chemotherapy or maintenance chemotherapy)

2. at least 3 half lives of any immunotherapy have passed

- for post allo-HCT subjects, CD3 chimerism >95% donor within 1 month of enrollment

- normal serum creatinine based on age/gender

- total bilirubin
- SF of >28% by ECHO or EF >50% by MUGA

- ALC of >/= 100 cells/ul

- pulse ox >/= 90% on room air

- agrees to highly effective contraception during and for 12 months after T cell infusion

- agrees to 15 years of follow up if they receive T cell infusion

- can tolerate apheresis

Exclusion Criteria:

- Has received immunosuppressant GVHD mediation in past 4 weeks

- Has active GVHD

- Systemic corticosteroids within 7 days of enrollment

- For Phase 1, has symptomatic CNS involvement of leukemia

- has detectable genetically modified cell therapy previously given

- has received virotherapy

- Hep C PCR positive

- HepB surface antigen positive

- HIV positive

- requires supplemental oxygen

- CXR show infectious process

- active clinically significant CNS dysfunction

- pregnant or breastfeeding

- has active malignancy other than CD19+ leukemia

- has active severe infection defined as positive blood culture wtih 48 hours of enrollment or fever above 38.2C and clinical signs of infection within 48 hours of study enrollment

- has concurrent medical condition that would prevent patient from undergoing protocol based therapy

- has primary immunodeficiency or bone marrow failure syndrome
Seattle Children's Hospital
Seattle, Washington, United States
Status: Recruiting
Contact: Rebecca Gardner, MD - 206-987-2106
Start Date
January 2014
Completion Date
January 2032
Seattle Children's Hospital
Seattle Children's Hospital
Record processing date
ClinicalTrials.gov processed this data on July 28, 2015
ClinicalTrials.gov page