Chronic Lymphocytic Leukemia Clinical Trial

A Pediatric Trial of Genetically Modified Autologous T Cells Directed Against CD19 for Relapsed CD19+ Acute Lymphoblastic Leukemia

Summary

Patients with relapsed leukemia often develop resistance to chemotherapy. For this reason, we are attempting to use a patient's own T cells, which can be genetically modified to expresses a chimeric antigen receptor(CAR). The CAR enables the T cell to recognize and kill the leukemic cells though the recognition of CD19, a protein expressed on the surface of the majority of pediatric ALL. This is a phase I study designed to determine the maximum tolerated dose of the CAR+ T cells and define the toxicity of the treatment. As a secondary aim, we will be looking at the efficacy of the T cells on eradicating the patient's leukemic cells.

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Full Description

Upon meeting the eligibility requirements and enrolling on study, subjects will undergo a blood draw to obtain the T cells for the generation of the CD19 CAR+ T cells. The T cells are isolated from the blood, transduced with a lentivirus to express the CD19 CAR, 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 will be admitted to the hospital to receive 2 days of cyclophosphamide for lymphodepletion and reduction of disease burden. Several days later, the subject will receive an infusion of the CAR+ T cells.

Following treatment with the CAR+ T cells, subjects will be intensely followed for 6 weeks with serial blood testing and re-evaluation of disease status with bone marrow aspirates. After 6 weeks, the subjects clinical care will be resumed by their primary oncologist, and it is possible that they would receive additionally chemotherapy or a stem cell transplant.

Upon completion of the study, subjects will be followed at least annually with a either a medical history, physical exam and blood tests or a phone call/questionnaire for 15 years. 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.

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Eligibility Criteria

Inclusion Criteria:

CD19+ Leukemia in 1st marrow relapse with MRD at the end of 1st month of re-induction
CD19+ Leukemia in 2nd or greater relapse
CD19+ Leukemia with indication for HCT, but has contraindication
Age between 1 and 26 years of age
Karnofsky of >50 or Lansky >50
Life Expectancy >12 weeks
Able to tolerate a blood draw of 4-6mL/kg
Recovered from acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy
absolute lymphocyte count of >/=750 cell/mm3 or >/=500 is >20kg
creatinine clearance or radioisotope GFR >/= 70mL/min/1.73m2 OR normal serum creatinine based on age/gender
total bilirubin ALT corrected QTc <450msec of ECG
Shortening Fraction >28% by ECHO or Ejection Fraction >50% by MUGA
Documented negative HIV, Hep B and Hep C
Agree to long-term follow up for up to 15 years if they receive T cell infusion

Exclusion Criteria:

Philadelphia Positive Leukemia
Prior Allogeneic Stem Cell Transplant
CNS 2 or 3
prior cellular immunotherapy with chimeric antigen receptor modified T cells
fully humanized antibodies within three half lives
systemic corticosteroids within 7 days of enrollment
requires supplemental oxygen or has a chest X-ray with an infectious process
CNS pathology (seizure disorder, paresis, aphasia, cerebrovascular ischemia/hemorrhage, severe brain injuries, dementia, cerebellar disease, organic brain syndrome, psychosis, coordination or movement disorder)
Pregnant or breastfeeding women. Female participant of reproductive age must have a negative pregnancy test and agree to contraception for 1 year after T cell infusion.
Active Malignancy other than CD19+ Leukemia
Active severe infection defined as a positive blood culture within 48 hours of study enrollment or a fever >38.2C AND clinical signs of infection within 48 hours of study enrollment
Patient has a concurrent medical condition, that in the opinion of the protocol PI or designee, would prevent the patient from undergoing protocol-based therapy.
Trisomy 21
Primary immunodeficiency/bone marrow failure syndrome

Study is for people with:

Chronic Lymphocytic Leukemia

Phase:

Phase 1

Estimated Enrollment:

6

Study ID:

NCT01683279

Recruitment Status:

Active, not recruiting

Sponsor:

Seattle Children's Hospital

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There is 1 Location for this study

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Seattle Children's Hospital
Seattle Washington, 98105, United States

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Study is for people with:

Chronic Lymphocytic Leukemia

Phase:

Phase 1

Estimated Enrollment:

6

Study ID:

NCT01683279

Recruitment Status:

Active, not recruiting

Sponsor:


Seattle Children's Hospital

How clear is this clinincal trial information?

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