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

Primary Purpose

B Cell Leukemia

Status
Active
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Autologous CD19 CAR+ EGFTt + T cells
Sponsored by
Seattle Children's Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for B Cell Leukemia focused on measuring pediatric, acute lymphoblastic leukemia, CD19, Chimeric Antigen Receptor

Eligibility Criteria

1 Year - 26 Years (Child, Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Seattle Children's Hospital

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

CAR+ T cells

Arm Description

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

Outcomes

Primary Outcome Measures

Number of Participant with Adverse Events
The safety of the T cell infusion will be described and the maximum tolerated dose determined.

Secondary Outcome Measures

Persistence of the CD19 CAR+ T cells
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
Patients will have their bone marrow assessed following the T cell infusion to determine if their disease responded to the treatment

Full Information

First Posted
September 7, 2012
Last Updated
June 27, 2023
Sponsor
Seattle Children's Hospital
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1. Study Identification

Unique Protocol Identification Number
NCT01683279
Brief Title
A Pediatric Trial of Genetically Modified Autologous T Cells Directed Against CD19 for Relapsed CD19+ Acute Lymphoblastic Leukemia
Official Title
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
Study Type
Interventional

2. Study Status

Record Verification Date
June 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
March 25, 2012 (Actual)
Primary Completion Date
January 7, 2015 (Actual)
Study Completion Date
January 7, 2030 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Seattle Children's Hospital

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
B Cell Leukemia
Keywords
pediatric, acute lymphoblastic leukemia, CD19, Chimeric Antigen Receptor

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
6 (Actual)

8. Arms, Groups, and Interventions

Arm Title
CAR+ T cells
Arm Type
Experimental
Arm Description
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 Type
Biological
Intervention Name(s)
Autologous CD19 CAR+ EGFTt + T cells
Intervention Description
Autologous T cell modified to express a CD19 specific CAR and a truncated EGFRt tag
Primary Outcome Measure Information:
Title
Number of Participant with Adverse Events
Description
The safety of the T cell infusion will be described and the maximum tolerated dose determined.
Time Frame
42 days
Secondary Outcome Measure Information:
Title
Persistence of the CD19 CAR+ T cells
Description
Patients will be followed for 42 days to determine if the transferred T cells remain detectable in the blood and bone marrow
Time Frame
42 days
Title
Determine if there is anti-leukemic activity of the CD19 CAR+ T cells
Description
Patients will have their bone marrow assessed following the T cell infusion to determine if their disease responded to the treatment
Time Frame
42 days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
1 Year
Maximum Age & Unit of Time
26 Years
Accepts Healthy Volunteers
No
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 </= 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Rebecca Gardner, MD
Organizational Affiliation
Seattle Children's Hospital
Official's Role
Study Chair
Facility Information:
Facility Name
Seattle Children's Hospital
City
Seattle
State/Province
Washington
ZIP/Postal Code
98105
Country
United States

12. IPD Sharing Statement

Learn more about this trial

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

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