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

NCT01683279 | Active Not Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: PLAT-01
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

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.

Conditions

B Cell Leukemia

Keywords

pediatric; acute lymphoblastic leukemia; CD19; Chimeric Antigen Receptor

Outcome Measures

Primary Outcomes (1)

• Number of Participant with Adverse Events

  The safety of the T cell infusion will be described and the maximum tolerated dose determined.

  42 days

Secondary Outcomes (2)

• Persistence of the CD19 CAR+ T cells

  42 days

• Determine if there is anti-leukemic activity of the CD19 CAR+ T cells

  42 days

Study Arms (1)

CAR+ T cells

EXPERIMENTAL

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

Biological: Autologous CD19 CAR+ EGFTt + T cells

Interventions

Autologous CD19 CAR+ EGFTt + T cells BIOLOGICAL

Autologous T cell modified to express a CD19 specific CAR and a truncated EGFRt tag

CAR+ T cells

Eligibility Criteria

• Age: 1 Year - 26 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Seattle Children's Hospital: lead

Study Sites (1)

Seattle Children's Hospital

Seattle, Washington, 98105, United States

Location

MeSH Terms

Conditions

Leukemia, B-Cell; Precursor Cell Lymphoblastic Leukemia-Lymphoma

Condition Hierarchy (Ancestors)

Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• Colleen Annesley, MD

  Seattle Children's Hospital

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Medical Director, Seattle Children's Therapeutics

Study Record Dates

• First Submitted: September 7, 2012
• First Posted: September 11, 2012
• Study Start: March 25, 2012
• Primary Completion: January 7, 2015
• Study Completion (Estimated): January 7, 2030
• Last Updated: June 17, 2025

Record last verified: 2025-06

Locations

US (1)