Skip to content
Triangle logo TriangleGet started
← Study library

NCT02028455 · CITED IN SOURCE DOCUMENTS

A Pediatric and Young Adult Trial of Genetically Modified T Cells Directed Against CD19 for Relapsed/Refractory CD19+ Leukemia

An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.

Phase
PHASE1, PHASE2
Status at capture
ACTIVE NOT RECRUITING
Registry last update
2026-08-06

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.

Open the original ClinicalTrials.gov record → · Download preserved record

What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

flow

Participant flow

→

baseline

Baseline characteristics

→

outcome · POSTED

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

→

outcome · POSTED

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

→

outcome · POSTED

Number of Participants Who Have a Releasable Cell Product Generated

→

outcome · POSTED

Persistence of Functional CD19 CAR+ T Cells

→

outcome · POSTED

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

→

outcome · POSTED

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

→

adverse events

Adverse events

→

more info

Limitations, agreements, and source contact

→
Who could take part
eligibility Criteria
Inclusion Criteria: 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. \[N.B. Study closed to enrollment of leukemia subjects\] OR No prior history of allogeneic HCT (one of the following) * 2nd or greater relapse, with or without extramedullary disease (isolated extramedullary disease is eligible) * 1st 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 OR 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) No systemic corticosteroids (unless physiologic replacement dosing) within 7 days of enrollment. No prior genetically modified cell therapy that is still detectable or virotherapy allowed. * Normal serum creatinine based on age/gender * Total bilirubin \</3x ULN OR conjugated bilirubin \</2mg/dl * ALT \</5X ULN * SF of \>28% by ECHO or EF \>50% by MUGA * ALC of \>/= 100 cells/ul * Pulse ox \>/= 90% on room air Patient must have documented negative HIV antigen and antibody, Hepatitis B surface antigen, and Hepatitis C antibody within 3 months prior to enrollment. For patient with positive Hepatitis C Ab, negative PCR testing must be documented in order to be eligible. Patients must NOT have active clinically significant CNS dysfunction (including but not limited to such as uncontrolled seizure disorder, paresis, aphasia, cerebrovascular ischemia/hemorrhage, severe brain injuries, dementia, cerebellar disease, organic brain syndrome, psychosis, coordination or movement disorder) Must agree to highly effective contraception during and for 12 months after T cell infusion. Patients must be able to tolerate apheresis procedure, including placement of temporary apheresis line if required. Patients must NOT have an active malignancy other than CD19+ leukemia. Patients must NOT have an active severe infection defined as: * A positive blood culture within 48 hours of study enrollment * A fever above 38.2 C AND clinical signs of infection within 48 hours of study enrollment Patients must NOT have any concurrent medical condition that, in the opinion of the PI or designee, would prevent the patient from undergoing protocol-based therapy. Patients with a primary immunodeficiency/ bone marrow failure syndrome are excluded from this trial. Research participant or parent/legal guardian must agree to participate in long-term follow-up for up to 15 years, if they are enrolled in the study and receive T-cell infusion.
healthy Volunteers
false
maximum Age
26 Years
minimum Age
1 Year
sex
ALL
std Ages
  1. CHILD
  2. ADULT
Treatment arms and interventions
arm Groups
  1. description
    This phase 1 cohort will receive Patient Derived CD19 specific CAR T cells at a dose of 5x10\^5 CAR T cells/kg
    intervention Names
    1. Biological: Patient Derived CD19 specific CAR T cells also expressing an EGFRt
    label
    Phase 1 - Cohort 1A
    type
    EXPERIMENTAL
  2. description
    This phase 1 cohort will receive Patient Derived CD19 specific CAR T cells at a dose of 1x10\^6 CAR T cells/kg
    intervention Names
    1. Biological: Patient Derived CD19 specific CAR T cells also expressing an EGFRt
    label
    Phase 1 - Cohort 1B
    type
    EXPERIMENTAL
  3. description
    This phase 1 cohort will receive Patient Derived CD19 specific CAR T cells at a dose of 5x10\^6 CAR T cells/kg
    intervention Names
    1. Biological: Patient Derived CD19 specific CAR T cells also expressing an EGFRt
    label
    Phase 1 - Cohort 1C
    type
    EXPERIMENTAL
  4. description
    This phase 1 cohort will receive Patient Derived CD19 specific CAR T cells at a dose of 1x10\^7 CAR T cells/kg
    intervention Names
    1. Biological: Patient Derived CD19 specific CAR T cells also expressing an EGFRt
    label
    Phase 1 - Cohort 1D
    type
    EXPERIMENTAL
  5. description
    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
    intervention Names
    1. Biological: Patient Derived CD19 specific CAR T cells also expressing an EGFRt
    label
    Phase 1 - Cohort 1F1
    type
    EXPERIMENTAL
  6. description
    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
    intervention Names
    1. Biological: Patient Derived CD19 specific CAR T cells also expressing an EGFRt
    label
    Phase 1 - Cohort 1F2
    type
    EXPERIMENTAL
  7. description
    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.
    intervention Names
    1. Biological: Patient Derived CD19 specific CAR T cells also expressing an EGFRt
    label
    Phase 2
    type
    EXPERIMENTAL
interventions
  1. arm Group Labels
    1. Phase 1 - Cohort 1A
    2. Phase 1 - Cohort 1B
    3. Phase 1 - Cohort 1C
    4. Phase 1 - Cohort 1D
    5. Phase 1 - Cohort 1F1
    6. Phase 1 - Cohort 1F2
    7. Phase 2
    description
    Defined Composition CD4 and CD8 T cells Lentivirally Transduced to Express a Second Generation 4-1BB:zeta CD19 CAR and EGFRt
    name
    Patient Derived CD19 specific CAR T cells also expressing an EGFRt
    type
    BIOLOGICAL
Study design
allocation
NON_RANDOMIZED
intervention Model
SEQUENTIAL
masking Info
masking
NONE
primary Purpose
TREATMENT
Enrollment
count
167
type
ACTUAL
Registered outcome plans (not posted results)
primary Outcomes
  1. description
    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
    measure
    Number of Participants Who Experienced an Adverse Event Meeting the Dose-Limiting Toxicity Definition
    time Frame
    Initial CAR T cell infusion through 30 days post infusion
  2. description
    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
    measure
    Number of Participants With an MRD Negative Complete Remission After Initial CAR T Cell Infusion
    time Frame
    Initial CAR T cell infusion through Day 63 post infusion assessment (+/- 14 days)
  3. description
    The feasibility of manufacturing and releasing T cell products from pediatric and young adult patients with CD19+ relapsed or refractory leukemia
    measure
    Number of Participants Who Have a Releasable Cell Product Generated
    time Frame
    Up to 28 days per manufacturing attempt
secondary Outcomes
  1. description
    Participants will be followed for 63 days to determine if the transferred T cells remain detectable in the blood and bone marrow
    measure
    Persistence of Functional CD19 CAR+ T Cells
    time Frame
    Initial CAR T Infusion through Day 63 post infusion assessment (+/- 14 days)
  2. measure
    Number of Participants With Recrudescence or Development of Acute GVHD (Graft Versus Host Disease) Symptoms Post CAR T Infusion
    time Frame
    Initial CAR T Infusion through Day 63 post infusion assessment (+/- 14 days)
  3. description
    The efficacy of cetuximab to ablate the T cells will be measured by loss of detection of T cells and any associated toxicities as well as facilitating B cell recovery.
    measure
    Number of Participants That Received Cetuximab Who Have T Cells Successfully Ablated
    time Frame
    3 years
Full study description
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.
detailed Description
Upon meeting the eligibility requirements and enrolling on study, subjects will undergo apheresis to obtain the T cells for the generation of the CD19 CAR+ T cells. In patients with a prior history of allogeneic HCT, the T cells obtained are of donor origin. The T cells are isolated from the apheresis product, the CD4 and CD8 T cells are then selected and grown separately, transduced with a lentivirus to express the CD19 CAR as well as a truncated EGFR that has no signaling capacity (noted EGFRt) 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 determination if lymphodepletion is necessary. A variety of lymphodepletion strategies are acceptable and determined on a case by case basis. At least 48 hours after the completion of lymphodepletion, the subject will receive and infusion of CAR+ T cells at an approximate 1:1 ratio of CD4 to CD8 CAR+ T cells. Following treatment with the CAR+ T cells, subjects will be followed intensely for 2 months with serial blood testing and re-evaluation of disease status with bone marrow aspirates. After 2 months, the subjects clinical care will be resumed by their primary oncologist, and it is possible that they would receive additional chemotherapy or HCT. Some subjects will receive cetuximab for ablation of the genetically modified T cells. Criteria to receive cetuximab include acute toxicities that are life threatening, as well as an ongoing remission with continued B cell aplasia. Upon completion of the study, subjects will be followed bi-annually for 5 years, and then annually for 10 additional years with either a medical history, physical exam and blood tests or a phone call/questionnaire. 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.
Source references
references
  1. citation
    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
    40233328
    type
    DERIVED
  2. citation
    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
    35580141
    type
    DERIVED
  3. citation
    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
    34515338
    type
    DERIVED
  4. citation
    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
    30860496
    type
    DERIVED
  5. citation
    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
    28408462
    type
    DERIVED
  6. citation
    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
    26907630
    type
    DERIVED
Source notices and limitations
    Discovery and provenance
    1. release id
      ctgov-registry-7ad944f6deaf1f5cd6122126
      edge id
      nct-edge-a19fc3c3c42a2e3b4405
      requested nct id
      NCT02028455
      primary nct id
      NCT02028455
      source kind
      nci_explicit_reference_or_link
      source record id
      Source null
      source file sha256
      8416f6a719c496873bd76f9837e64f45de187c289bc5ec0bf994c3e18f233983
      payload sha256
      5f086772096d96b612af1b0d60637d307cb14a4ca6e8a80e2b33b00ca8f9d273
      payload
      clinical indication matching status
      not_inferred
      end exclusive
      true
      id
      nct-edge-a19fc3c3c42a2e3b4405
      link basis
      explicit_NCT_identifier_in_acquired_source
      nct id
      NCT02028455
      occurrences
      1. context exact
        class="lower-alpha"><li>A study of 50 patients eligible for HSCT after 4-1BB-based CAR T-cell therapy reported the following results (<a href="/clinicaltrials/NCT02028455">PLAT-02 [NCT02028455]</a> trial):[<a href="#cit/section_10.201">201</a>]<div class="pdq-content-list"><ul id="_2476"><li>Patients who lost CAR T-cell function
        end
        1012552
        exact text
        NCT02028455
        start
        1012541
      2. context exact
        li>A study of 50 patients eligible for HSCT after 4-1BB-based CAR T-cell therapy reported the following results (<a href="/clinicaltrials/NCT02028455">PLAT-02 [NCT02028455]</a> trial):[<a href="#cit/section_10.201">201</a>]<div class="pdq-content-list"><ul id="_2476"><li>Patients who lost CAR T-cell function before 63 days after
        end
        1012574
        exact text
        NCT02028455
        start
        1012563
      offset unit
      unicode_code_points
      source file
      /tmp/cancer-full-research/nci/raw/346ccc02fe964bb078.html
      source file sha256
      8416f6a719c496873bd76f9837e64f45de187c289bc5ec0bf994c3e18f233983
      source json pointer
      Source null
      source kind
      nci_explicit_reference_or_link
      source record id
      Source null
      source retrieved at
      2026-09-09T23:21:53.377184+00:00
      source string basis
      UTF-8_text_with_universal_newline_translation
      source string sha256
      d68ab4be374e916e0de9c7632347ccef2167b36c83a023ce62cc9bb0575973b9
      source title
      Childhood Acute Lymphoblastic Leukemia Treatment (PDQ®)–Health Professional Version
      source update dates
      1. context
        Updated: April 21, 2025
        datetime
        2025-04-21T12:00:00Z
        display
        April 21, 2025

    Preserved source evidence · Not medical advice