NCT02028455

Brief Summary

Patients with relapsed or refractory leukemia often develop resistance to chemotherapy. For this reason, we are attempting to use T cells obtained directly from the patient, which can be genetically modified to express a chimeric antigen receptor (CAR). The CAR enables the T cell to recognize and kill the leukemic cell through the recognition of CD19, a protein expressed of the surface of the leukemic cell in patients with CD19+ leukemia. This is a phase 1/2 study designed to determine the maximum tolerated dose of the CAR+ T cells as well as to determine the efficacy. The phase 1 cohort is restricted to those patients who have already had an allogeneic hematopoietic cell transplant (HCT). The phase 2 is open to all patients regardless of having a history of HCT.

Trial Health

75
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
167

participants targeted

Target at P75+ for phase_1

Timeline
124mo left

Started Feb 2014

Longer than P75 for phase_1

Geographic Reach
1 country

3 active sites

Status
active not recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress55%
Feb 2014Jul 2036

First Submitted

Initial submission to the registry

January 3, 2014

Completed
4 days until next milestone

First Posted

Study publicly available on registry

January 7, 2014

Completed
1 month until next milestone

Study Start

First participant enrolled

February 11, 2014

Completed
7.5 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

August 10, 2021

Completed
1.6 years until next milestone

Results Posted

Study results publicly available

March 14, 2023

Completed
13.3 years until next milestone

Study Completion

Last participant's last visit for all outcomes

July 1, 2036

Expected
Last Updated

August 27, 2025

Status Verified

August 1, 2025

Enrollment Period

7.5 years

First QC Date

January 3, 2014

Results QC Date

August 9, 2022

Last Update Submit

August 7, 2025

Conditions

CD19+ Acute Leukemia

Keywords

pediatricyoung adultacute lymphoblastic leukemiaCD19leukemiaChimeric Antigen ReceptorT cell

Outcome Measures

Primary Outcomes (3)

  • Number of Participants Who Experienced an Adverse Event Meeting the Dose-Limiting Toxicity Definition

    The safety of the T cell infusion at the maximum tolerated dose determined in Phase 1, and further characterized in Phase 2, will be described

    Initial CAR T cell infusion through 30 days post infusion

  • Number of Participants With an MRD Negative Complete Remission After Initial CAR T Cell Infusion

    The efficacy of the T cell infusion will be estimated based on the number of participants who have an MRD negative bone marrow aspirate following the initial T cell infusion

    Initial CAR T cell infusion through Day 63 post infusion assessment (+/- 14 days)

  • Number of Participants Who Have a Releasable Cell Product Generated

    The feasibility of manufacturing and releasing T cell products from pediatric and young adult patients with CD19+ relapsed or refractory leukemia

    Up to 28 days per manufacturing attempt

Secondary Outcomes (3)

  • Persistence of Functional CD19 CAR+ T Cells

    Initial CAR T Infusion through Day 63 post infusion assessment (+/- 14 days)

  • Number of Participants With Recrudescence or Development of Acute GVHD (Graft Versus Host Disease) Symptoms Post CAR T Infusion

    Initial CAR T Infusion through Day 63 post infusion assessment (+/- 14 days)

  • Number of Participants That Received Cetuximab Who Have T Cells Successfully Ablated

    3 years

Study Arms (7)

Phase 1 - Cohort 1A

EXPERIMENTAL

This phase 1 cohort will receive Patient Derived CD19 specific CAR T cells at a dose of 5x10\^5 CAR T cells/kg

Biological: Patient Derived CD19 specific CAR T cells also expressing an EGFRt

Phase 1 - Cohort 1B

EXPERIMENTAL

This phase 1 cohort will receive Patient Derived CD19 specific CAR T cells at a dose of 1x10\^6 CAR T cells/kg

Biological: Patient Derived CD19 specific CAR T cells also expressing an EGFRt

Phase 1 - Cohort 1C

EXPERIMENTAL

This phase 1 cohort will receive Patient Derived CD19 specific CAR T cells at a dose of 5x10\^6 CAR T cells/kg

Biological: Patient Derived CD19 specific CAR T cells also expressing an EGFRt

Phase 1 - Cohort 1D

EXPERIMENTAL

This phase 1 cohort will receive Patient Derived CD19 specific CAR T cells at a dose of 1x10\^7 CAR T cells/kg

Biological: Patient Derived CD19 specific CAR T cells also expressing an EGFRt

Phase 1 - Cohort 1F1

EXPERIMENTAL

This phase 1 cohort will receive Patient Derived CD19 specific CAR T cells at a dose of 5x10\^5 CAR T cells/kg following prescribed lymph-depletion with fludarabine and cyclophosphamide

Biological: Patient Derived CD19 specific CAR T cells also expressing an EGFRt

Phase 1 - Cohort 1F2

EXPERIMENTAL

This phase 1 cohort will receive Patient Derived CD19 specific CAR T cells at a dose of 1x10\^6 CAR T cells/kg following prescribed lymph-depletion with fludarabine and cyclophosphamide

Biological: Patient Derived CD19 specific CAR T cells also expressing an EGFRt

Phase 2

EXPERIMENTAL

The phase 2 cohort will receive Patient Derived CD19 specific CAR T cells at a dose of 1 x 10\^6 CAR T cells/kg following lymphodepletion if indicated.

Biological: Patient Derived CD19 specific CAR T cells also expressing an EGFRt

Interventions

Patient Derived CD19 specific CAR T cells also expressing an EGFRtBIOLOGICAL

Defined Composition CD4 and CD8 T cells Lentivirally Transduced to Express a Second Generation 4-1BB:zeta CD19 CAR and EGFRt

Phase 1 - Cohort 1APhase 1 - Cohort 1BPhase 1 - Cohort 1CPhase 1 - Cohort 1DPhase 1 - Cohort 1F1Phase 1 - Cohort 1F2Phase 2

Eligibility Criteria

Age1 Year - 26 Years
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17), Adult (18-64)

You may qualify if:

  • Patients must be ≥12 months of age and \<27 years of age at the time of study enrollment.
  • Must be ≥10kg
  • Confirmed CD19+ leukemia recurrence defined as ≥0.01% disease in the marrow or isolated extramedullary disease following allogeneic HCT. \[N.B. Study closed to enrollment of leukemia subjects\]
  • No prior history of allogeneic HCT (one of the following)
  • nd or greater relapse, with or without extramedullary disease (isolated extramedullary disease is eligible)
  • st marrow relapse at end of 1st month of re-induction with marrow having ≥0.01% blast disease, with or without extramedullary disease
  • Primary Refractory as defined as having M2 or M3 marrow after induction
  • Subject has indication for HCT but has been deemed ineligible
  • CD19+ Non-Hodgkin Lymphoma (NHL) refractory or relapsed with no known curative therapies available \[N.B. Study remains open to enrollment of lymphoma subjects\]
  • Patients with CNS involvement are eligible provided that they are asymptomatic and in the opinion of the study PI have a reasonable expectation that disease burden can be controlled in the interval between enrollment and T cell infusion. Patients that have a significant neurologic deterioration will be not be eligible for T cell infusion until alternate therapies result in neurological stabilization.
  • Patients must have a Lansky performance status score of ≥50 or a Karnofsky score of ≥ 50 for patients ≥16 years of age.
  • Life Expectancy of \>8 weeks
  • Patients must be free from active GVHD and off immunosuppressive GVHD therapy for 4 weeks prior to enrollment.
  • Recovered from acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy
  • It must be at least 7 days since last chemotherapy was administered (this does not include intrathecal chemotherapy or maintenance chemotherapy)
  • +18 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (3)

Children's Hospital Los Angeles

Los Angeles, California, 90027, United States

Location

Children's Hospital Oakland

Oakland, California, 94609, United States

Location

Seattle Children's Hospital

Seattle, Washington, 98105, United States

Location

Related Publications (6)

  • Annesley C, Seidel K, Wu Q, Summers C, Wayne AS, Pulsipher MA, Agrawal AK, Brown CT, Mgebroff S, Lindgren C, Rawlings-Rhea S, Huang W, Wilson AL, Jensen MC, Park JR, Gardner RA. Outcomes of PLAT-02 and PLAT-03: evaluating CD19 CAR T-cell therapy and CD19-expressing T-APC support in pediatric B-ALL. Blood. 2025 Aug 14;146(7):789-801. doi: 10.1182/blood.2025028359.

    PMID: 40233328DERIVED

  • Ceppi F, Wilson AL, Annesley C, Kimmerly GR, Summers C, Brand A, Seidel K, Wu QV, Beebe A, Brown C, Mgebroff S, Lindgren C, Rawlings-Rhea SD, Huang W, Pulsipher MA, Wayne AS, Park JR, Jensen MC, Gardner RA. Modified Manufacturing Process Modulates CD19CAR T-cell Engraftment Fitness and Leukemia-Free Survival in Pediatric and Young Adult Subjects. Cancer Immunol Res. 2022 Jul 1;10(7):856-870. doi: 10.1158/2326-6066.CIR-21-0501.

    PMID: 35580141DERIVED

  • Ernst M, Oeser A, Besiroglu B, Caro-Valenzuela J, Abd El Aziz M, Monsef I, Borchmann P, Estcourt LJ, Skoetz N, Goldkuhle M. Chimeric antigen receptor (CAR) T-cell therapy for people with relapsed or refractory diffuse large B-cell lymphoma. Cochrane Database Syst Rev. 2021 Sep 13;9(9):CD013365. doi: 10.1002/14651858.CD013365.pub2.

    PMID: 34515338DERIVED

  • Finney OC, Brakke HM, Rawlings-Rhea S, Hicks R, Doolittle D, Lopez M, Futrell RB, Orentas RJ, Li D, Gardner RA, Jensen MC. CD19 CAR T cell product and disease attributes predict leukemia remission durability. J Clin Invest. 2019 Mar 12;129(5):2123-2132. doi: 10.1172/JCI125423. Print 2019 May 1.

    PMID: 30860496DERIVED

  • Gardner RA, Finney O, Annesley C, Brakke H, Summers C, Leger K, Bleakley M, Brown C, Mgebroff S, Kelly-Spratt KS, Hoglund V, Lindgren C, Oron AP, Li D, Riddell SR, Park JR, Jensen MC. Intent-to-treat leukemia remission by CD19 CAR T cells of defined formulation and dose in children and young adults. Blood. 2017 Jun 22;129(25):3322-3331. doi: 10.1182/blood-2017-02-769208. Epub 2017 Apr 13.

    PMID: 28408462DERIVED

  • Gardner R, Wu D, Cherian S, Fang M, Hanafi LA, Finney O, Smithers H, Jensen MC, Riddell SR, Maloney DG, Turtle CJ. Acquisition of a CD19-negative myeloid phenotype allows immune escape of MLL-rearranged B-ALL from CD19 CAR-T-cell therapy. Blood. 2016 May 19;127(20):2406-10. doi: 10.1182/blood-2015-08-665547. Epub 2016 Feb 23.

    PMID: 26907630DERIVED

MeSH Terms

Conditions

Precursor Cell Lymphoblastic Leukemia-LymphomaLeukemia

Condition Hierarchy (Ancestors)

Leukemia, LymphoidNeoplasms by Histologic TypeNeoplasmsHematologic DiseasesHemic and Lymphatic DiseasesLymphoproliferative DisordersLymphatic DiseasesImmunoproliferative DisordersImmune System Diseases

Results Point of Contact

Title
Dr. Colleen Annesley
Organization
Seattle Children's Therapeutics
ICC-PLAT@seattlechildrens.org
206-987-7122

Study Officials

  • Colleen Annesley, MD

    Seattle Children's Hospital

    STUDY CHAIR

Publication Agreements

PI is Sponsor Employee
No
Restrictive Agreement
No

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
SEQUENTIAL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Medical Director, Seattle Children's Therapeutics

Study Record Dates

First Submitted

January 3, 2014

First Posted

January 7, 2014

Study Start

February 11, 2014

Primary Completion

August 10, 2021

Study Completion (Estimated)

July 1, 2036

Last Updated

August 27, 2025

Results First Posted

March 14, 2023

Record last verified: 2025-08

Locations

US(3)