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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01683279
Recruitment Status : Active, not recruiting
First Posted : September 11, 2012
Last Update Posted : January 19, 2021
Sponsor:
Information provided by (Responsible Party):
Rebecca Gardner, Seattle Children's Hospital

Tracking Information
First Submitted Date  ICMJE September 7, 2012
First Posted Date  ICMJE September 11, 2012
Last Update Posted Date January 19, 2021
Actual Study Start Date  ICMJE March 25, 2012
Actual Primary Completion Date January 7, 2015   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 7, 2012)
Number of Participant with Adverse Events [ Time Frame: 42 days ]
The safety of the T cell infusion will be described and the maximum tolerated dose determined.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: September 7, 2012)
  • Persistence of the CD19 CAR+ T cells [ Time Frame: 42 days ]
    Patients will be followed for 42 days to determine if the transferred T cells remain detectable in the blood and bone marrow
  • Determine if there is anti-leukemic activity of the CD19 CAR+ T cells [ Time Frame: 42 days ]
    Patients will have their bone marrow assessed following the T cell infusion to determine if their disease responded to the treatment
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Pediatric Trial of Genetically Modified Autologous T Cells Directed Against CD19 for Relapsed CD19+ Acute Lymphoblastic Leukemia
Official Title  ICMJE 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
Brief 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.
Detailed 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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE B Cell Leukemia
Intervention  ICMJE Biological: Autologous CD19 CAR+ EGFTt + T cells
Autologous T cell modified to express a CD19 specific CAR and a truncated EGFRt tag
Study Arms  ICMJE Experimental: CAR+ T cells
Subjects will receive two days of cyclophosphamide for a total of 3g/m^2 followed several days later by a single dose of Autologous CD19 CAR+ EGFTt + T cells
Intervention: Biological: Autologous CD19 CAR+ EGFTt + T cells
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: January 31, 2019)
6
Original Estimated Enrollment  ICMJE
 (submitted: September 7, 2012)
18
Estimated Study Completion Date  ICMJE January 7, 2030
Actual Primary Completion Date January 7, 2015   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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 </= 1.5x upper limit normal OR direct bilirubin </= 1.5mg/dl
  • ALT </= 3x upper limit normal
  • 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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 1 Year to 26 Years   (Child, Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01683279
Other Study ID Numbers  ICMJE PLAT-01
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Rebecca Gardner, Seattle Children's Hospital
Study Sponsor  ICMJE Seattle Children's Hospital
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Chair: Rebecca Gardner, MD Seattle Children's Hospital
PRS Account Seattle Children's Hospital
Verification Date January 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP