Pediatric Leukemia Adoptive Therapy (PLAT)-01: A Phase 1 Feasibility and Safety Study of Cellular Immunotherapy for Relapsed Pediatric CD19+ Acute Lymphoblastic Leukemia Using Autologous T-cells Lentivirally Transduced To Express a CD19-Specific Chimeric Antigen Receptor
1 Year
26 Years
Both
B Cell Leukemia
Trial Information
Pediatric Leukemia Adoptive Therapy (PLAT)-01: A Phase 1 Feasibility and Safety Study of Cellular Immunotherapy for Relapsed Pediatric CD19+ Acute Lymphoblastic Leukemia Using Autologous T-cells Lentivirally Transduced To Express a CD19-Specific Chimeric Antigen Receptor
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.
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
- Age between 18 and 26 years for the first 6 subjects enrolled and treated.
- will then open to subjects 1 to 26 years of age.
- Karnofsky of >70 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
- 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:
- Primary Refractory ALL
- Philadelphia Positive Leukemia
- Prior Allogeneic Stem Cell Transplant
- CNS 2 or 3
- >2 attempt at re-induction with current relapse
- for subjects <18 year of age, re-induction chemotherapy containing clofarabine or
cyclophosphamide (unless already has a useable T cell product generated during
previous enrollment)
- prior immunotherapy directed at CD19 (blinatumomab)
- 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
Type of Study:
Interventional
Study Design:
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Number of Participant with Adverse Events
Outcome Description:
The safety of the T cell infusion will be described and the maximum tolerated dose determined.
Outcome Time Frame:
42 days
Safety Issue:
Yes
Principal Investigator
Rebecca Gardner, MD
Investigator Role:
Principal Investigator
Investigator Affiliation:
Seattle Children's Hospital
Authority:
United States: Food and Drug Administration
Study ID:
PLAT-01
NCT ID:
NCT01683279
Start Date:
December 2012
Completion Date:
Related Keywords:
- B Cell Leukemia
- pediatric
- acute lymphoblastic leukemia
- CD19
- Chimeric Antigen Receptor
- Leukemia
- Leukemia, Lymphocytic, Chronic, B-Cell
- Leukemia, B-Cell
- Leukemia, Lymphoid
- Precursor Cell Lymphoblastic Leukemia-Lymphoma
Name | Location |
|---|---|
| Seattle Children's Hospital | Seattle, Washington 98105 |
