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B Acute Lymphoblastic LeukemiaPhase 1NCT02146924

Cellular Immunotherapy in Treating Patients With High-Risk Acute Lymphoblastic Leukemia

A Phase 1 study testing CD19CAR-CD28-CD3zeta-EGFRt-expressing Tcm-enriched T-lymphocytes, CD19CAR-CD28-CD3zeta-EGFRt-expressing Tn/mem-enriched T-lymphocytes and Laboratory Biomarker Analysis in people with B Acute Lymphoblastic Leukemia and Recurrent Acute Lymphoblastic Leukemia, run by City of Hope Medical Center at 1 site in United States.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
Search all trials

Trial summary

This phase I trial studies the side effects and best dose of cellular immunotherapy in treating patients with high-risk acute lymphoblastic leukemia. Placing a modified gene into white blood cells may help the body build an immune response to kill cancer cells. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
CD19CAR-CD28-CD3zeta-EGFRt-expressing Tcm-enriched T-lymphocytes, CD19CAR-CD28-CD3zeta-EGFRt-expressing Tn/mem-enriched T-lymphocytes and Laboratory Biomarker Analysis
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
71 participants
Where
1 siteUnited States
Study dates
16 Oct 2014to 17 Jun 2027
Phase
Phase 1
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • City of Hope (COH) pathology review confirms that research participant's diagnostic material is consistent with history of ALL with history of recurrence/progression/minimal residual disease (MRD) following prior therapy; additionally, CD19 positivity must be documented in a pathology report; however, it is not a requirement that the CD19 testing be performed by a COH pathologist; patients in second complete remission (CR2) or higher with history of CD19+ ALL on previous bone marrow biopsy are also eligible for the study
  • Research participants with confirmed 1st or higher relapse of disease by morphology, cytogenetics or molecular, or research participants with refractory or residual disease
  • Minimal residual disease (MRD) will be defined in this protocol by presence of malignant cells at 0.01% or more by flow cytometry or polymerase chain reaction (PCR) analysis at the completion of initial remission induction therapy
  • Participants with central nervous system (CNS) involvement by leukemia (CNS2 and CNS3) may be considered eligible after discussions with the study team.
  • Karnofsky performance status (KPS) of >= 70%
  • Life expectancy >= 16 weeks at time of enrollment
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  • Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control or abstinence) prior to study entry and for six months following duration of study participation; should a woman become pregnant or suspect that she is pregnant while participating on the trial, she should inform her treating physician immediately
  • All research participants must have the ability to understand and the willingness to sign a written informed consent
  • Note: For research participants who do not speak English, a short form consent may be used with a COH certified interpreter/translator to proceed with screening and leukapheresis, while the request for a translated full consent in processed; however, the research participant is allowed to proceed with lymphodepletion and T cell infusion only after the translated full consent form is signed
  • PROTOCOL-SPECIFIC CRITERIA:
  • COH pathology review confirms that research participant's diagnostic material is consistent with ALL; additionally, CD19 positivity must be documented in a pathology report; however it is not a requirement that the CD19 testing be performed by a COH pathologist
  • Negative serum pregnancy test for women of childbearing potential
  • If a research participant has undergone prior allogeneic stem cell transplant (alloSCT), and has documented =< grade 2 graft versus host disease (GVHD) but the donor is undergoing leukapheresis, the research participant may be considered eligible for enrollment (at the discretion of the study principal investigator [PI]) provided that immunosuppressants can be tapered off completely prior to lymphodepletion
  • If the research participant is to undergo leukapheresis, he/she must have a pretreatment calculated creatinine clearance of >= 50 mL/minute
  • If the research participant is to undergo leukapheresis, he/she must have a serum bilirubin =< 2.0 mg/dl
  • Note: in the event a participant has elevated levels of liver enzymes possibly related to underlying disease, the participant will still be considered eligible
  • If the research participant is to undergo leukapheresis, he/she must have alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 2.5 times the institutional upper limits of normal
  • Note: in the event a patient has elevated levels of liver enzymes possibly related to underlying disease, the patient will still be considered eligible
  • If the research participant is to undergo leukapheresis, he/she must have ejection fraction measured by echocardiogram or multigated acquisition scan (MUGA) > 45% (within 6 weeks of time of screening)
  • ELIGIBILITY TO PROCEED WITH PBMC COLLECTION
  • If research participant is undergoing leukapheresis he/she must have appropriate venous access
  • If research participant is undergoing leukapheresis, he/she must be at least 2 weeks from having received the last dose of immunosuppressant medications
  • Exceptions:
  • Steroids and tyrosine kinase inhibitors are allowed up to 7 days prior to leukapheresis
  • Research participant cannot be on more than 5 mg prednisone or equivalent doses of other corticosteroids at the time of leukapheresis
  • If research participant is undergoing leukapheresis and the research participant has undergone prior alloSCT, two months must have elapsed since allogeneic stem cell transplant to undergo PBMC collection for T cell manufacturing
  • If research participant is undergoing leukapheresis the last dose of prior chemotherapy, immunotherapy or radiation must be at least 2 weeks before the leukapheresis procedure
  • Exception rule: the wash out period for Hydrea is 48 hours
  • ELIGIBILITY TO UNDERGO LYMPHODEPLETION:
  • Please note that none of these criteria are applicable of the research participant's donor is undergoing leukapheresis
  • Research participant's absolute leukemic blast count does not exceed 10,000 cells/uL
  • Research participant has a released cryopreserved T cell product for T cell infusion on approximately day 0
  • KPS >= 70%
  • Non-hematological toxicity related to prior therapy must either have returned to =< grade 3, baseline, or deemed irreversible
  • Participants of reproductive potential must agree to use and utilize an adequate method of contraception throughout treatment and for at least 8 weeks after T cell infusion
  • Not requiring supplemental oxygen or mechanical ventilation, oxygen saturation 90% or higher on room air
  • Not requiring pressor support, no symptomatic cardiac arrhythmias, no acute coronary syndrome, or uncontrolled hypertension
  • Preservation of renal function, serum creatinine did NOT increase by more than 2 fold above the normal reference range
  • Total bilirubin =< 2.0 mg/dL
  • Note: in the event a participant has elevated levels of liver enzymes possibly related to underlying disease/disease progression, the participant will still be considered eligible
  • ALT and AST =< 2.5 times the institutional upper limits of normal
  • Note: in the event a participant has elevated levels of liver enzymes possibly related to underlying disease/disease progression, the participant will still be considered eligible
  • Research participants without clinically significant encephalopathy/new focal deficits
  • No clinical evidence of uncontrolled active infectious process
  • ELIGIBILITY CRITERIA AT TIME OF INFUSION OF GENETICALLY MODIFIED T CELLS:
  • Please note that none of these criteria are applicable of the research participant's donor is undergoing leukapheresis
  • Research participant has undergone lymphodepletion
  • Pulmonary: not requiring supplemental oxygen or mechanical ventilation, oxygen saturation 90% or higher on room air
  • Cardiovascular: not requiring pressor support, no symptomatic cardiac arrhythmias, no acute coronary syndrome, or uncontrolled hypertension
  • Renal function: preservation of renal function, serum creatinine did NOT increase by more than 2 fold above the normal reference range
  • Liver function: total bilirubin =< 2.0 mg/dL
  • Note: in the event a participant has elevated levels of liver enzymes possibly related to underlying disease/disease progression, the participant will still be considered eligible
  • Liver function: ALT and AST =< 2.5 times the institutional upper limits of normal
  • Note: in the event a participant has elevated levels of liver enzymes possibly related to underlying disease/disease progression, the participant will still be considered eligible
  • Research participant without clinically significant encephalopathy/new focal deficits
  • Infectious diseases: no clinical evidence of uncontrolled active infectious process
  • ELIGIBILITY CRITERIA TO UNDERGO OPTIONAL T CELL ABLATION:
  • Please note that none of these criteria are applicable of the research participant's donor is undergoing leukapheresis
  • Research participant is scheduled for an alloSCT
  • Research participant has >= 1% chimeric antigen receptor (CAR) modified T cells in the peripheral blood
  • Pulmonary criteria: not requiring supplemental oxygen or mechanical ventilation, oxygen saturation 90% or higher on room air
  • Cardiovascular criteria: not requiring pressor support, no symptomatic cardiac arrhythmias, no acute coronary syndrome, or uncontrolled hypertension
  • Renal function criteria: preservation of renal function, serum creatinine did NOT increase by more than 2 fold above the normal reference range
  • Liver function criteria: total bilirubin =< 2.0 mg/dL
  • Note: in the event a participant has elevated levels of liver enzymes possibly related to underlying disease/disease progression, the participant will still be considered eligible
  • Liver function criteria: AST and ALT =< 2.5 times the institutional upper limits of normal
  • Neurological: research participant without clinically significant encephalopathy/new focal deficits
  • Infectious diseases criteria: no clinical evidence of uncontrolled active infectious process

Who cannot join

  • Research participants with any uncontrolled illness including ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, poorly controlled pulmonary disease or psychiatric illness/social situations that would limit compliance with study requirements
  • Research participants with known active hepatitis B or C infection; research participants who are human immunodeficiency virus (HIV) positive based on testing performed within 4 weeks of enrollment; research participants with any signs or symptoms of active infection, positive blood cultures or radiological evidence of infections
  • Research participants receiving any other investigational agents, or concurrent biological, chemotherapy, or radiation therapy
  • Note: Please note that the above criterion is not applicable at the time of enrollment if the research participant's donor is undergoing leukapheresis
  • Research participants with presence of other active malignancy; however, research participants with history of prior malignancy treated with curative intent and in complete remission are eligible
  • Pregnant and lactating women
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  • Failure of research participant to understand the basic elements of the protocol and/or the risks/benefits of participating in this phase I study
  • History or presence of clinically relevant CNS pathology such as uncontrolled seizure disorder, recent stroke, severe brain injuries, dementia, cerebellar disease or psychosis
  • Any known contraindications to cyclophosphamide, fludarabine, etoposide, cetuximab or tocilizumab
  • Dependence on corticosteroids
  • Defined as doses of corticosteroids of greater than 5 mg/day of prednisone or equivalent doses of other corticosteroids
  • Note: topical and inhaled corticosteroids in standard doses and physiologic replacement for subjects with adrenal insufficiency are allowed
  • Please note that this criterion is not applicable at the time of enrollment if the research participant's donor is undergoing leukapheresis
  • Active autoimmune disease requiring systemic immunosuppressive therapy
  • Subjects, who in the opinion of the investigator, may not be able to comply with the safety monitoring requirements of the study

Trial locations and contacts

1 site in 1 country.

United States1 site

  • City of Hope Medical Center

    Duarte, California, 91010

Other trials in United States

About this study

Official title: Phase I Study to Evaluate Cellular Immunotherapy Using Memory-Enriched T Cells Lentivirally Transduced to Express a CD19-Specific, Hinge-Optimized, CD28-Costimulatory Chimeric Receptor and a Truncated EGFR Following Lymphodepleting Chemotherapy in Adult Patients With High-Risk CD19+ Acute Lymphoblastic Leukemia

This phase I trial studies the side effects and best dose of cellular immunotherapy in treating patients with high-risk acute lymphoblastic leukemia. Placing a modified gene into white blood cells may help the body build an immune response to kill cancer cells.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To examine the activity and safety of adoptive therapy using ex vivo expanded memory T cells that are enriched and genetically-modified to express a CD19-specific, hinge optimized, CD28-costimulatory chimeric antigen receptor (CAR) as well as a truncated human EGFR (Arm 1: CD19R(EQ)28zeta/truncated human EGFR [EGFRt]+ central memory T cells [TCM]; Arm 2: CD19R(EQ)28zeta/EGFRt+ naive and memory T cells [TN/NEM]) shortly following a lymphodepleting preparative regimen for adults with poor prognosis CD19+ acute lymphoblastic leukemia (ALL).

II. To determine the Phase II recommended dose (RP2D). III. To expand the maximum tolerated dose (MTD) dose to better describe the activity and safety of this dose.

SECONDARY OBJECTIVE:

  1. To study additional antitumor activity endpoints of CD19R(EQ)28zeta/EGFRt+ TCM and CD19R(EQ)28zeta/EGFRt+ TN/NEM.

OUTLINE: This is a dose-escalation study.

ARM I (CLOSED TO ACCRUAL JANUARY 2019): Patients receive lymphodepleting regimen per treating physician's discretion 3-14 days before the T-cell infusion. Patients receive CD19CAR-CD28-CD3zeta-EGFRt-expressing Tcm-enriched T cells IV over 15 minutes on day 0. Patients who have evidence of disease, whose tumor(s) continue to express the appropriate antigen target may receive an optional second infusion of CD19CAR-CD28-CD3zeta-EGFRt-expressing Tcm-enriched T cells after 28 days.

ARM II: Patients receive lymphodepleting regimen per treating physician's discretion 3-14 days before the T-cell infusion. Patients receive CD19CAR-CD28-CD3zeta-EGFRt-expressing Tn/nem-enriched T cells IV over 15 minutes on day 0. Patients who have evidence of disease, whose tumor(s) continue to express the appropriate antigen target may receive an optional second infusion of CD19CAR-CD28-CD3zeta-EGFRt-expressing Tn/nem-enriched T cells after 28 days.

After completion of study treatment, patients are followed up at 24 hours, weekly for 1 month, monthly for 1 year, and then yearly for at least 15 years.

Being tested
CD19CAR-CD28-CD3zeta-EGFRt-expressing Tcm-enriched T-lymphocytes, CD19CAR-CD28-CD3zeta-EGFRt-expressing Tn/mem-enriched T-lymphocytes, Laboratory Biomarker Analysis
Medical subject headings
Burkitt Lymphoma, Precursor Cell Lymphoblastic Leukemia-Lymphoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • CD19CAR-CD28-CD3zeta-EGFRt-expressing Tcm-enriched T-lymphocytesBiological

    Also called CD19-CAR-specific/truncated EGFR Lentiviral Vector-transduced T Cells, CD19CAR-CD28-CD3zeta-EGFRt-expressing Tcm-enriched T Cells, CD19R(EQ)28zeta/EGFRt+ TCM, CD19R(EQ)28zeta/truncated Human EGFR+ Central Memory T Cells

    Given IV

  • CD19CAR-CD28-CD3zeta-EGFRt-expressing Tn/mem-enriched T-lymphocytesBiological

    Also called CD19CAR-CD28-CD3zeta-EGFRt-expressing Tn/mem-enriched T Cells, CD19R(EQ)28zeta/EGFRt+ Naive and Memory T Cells, CD19R(EQ)28zetaEGFRt+ Tn/mem Cells

    Given IV

  • Laboratory Biomarker AnalysisOther

    Correlative studies

Study groups in NCT02146924
Study groupRoleWhat they receive
Arm I (cellular immunotherapy closed to accrual January 2019)ExperimentalPatients receive lymphodepleting regimen per treating physician's discretion 3-14 days before the T-cell infusion. Patients receive CD19CAR-CD28-CD3zeta-EGFRt-expressing Tcm-enriched T cells IV over 15 minutes on day 0. Patients who have evidence of disease, whose tumor(s) continue to express the appropriate antigen target may receive an optional second infusion of CD19CAR-CD28-CD3zeta-EGFRt-expressing Tcm-enriched T cells after 28 days.
Receives: Biological: CD19CAR-CD28-CD3zeta-EGFRt-expressing Tcm-enriched T-lymphocytes; Other: Laboratory Biomarker Analysis
Arm II (cellular immunotherapy)Active comparatorPatients receive lymphodepleting regimen per treating physician's discretion 3-14 days before the T-cell infusion. Patients receive CD19CAR-CD28-CD3zeta-EGFRt-expressing Tn/nem-enriched T cells IV over 15 minutes on day 0. Patients who have evidence of disease, whose tumor(s) continue to express the appropriate antigen target may receive an optional second infusion of CD19CAR-CD28-CD3zeta-EGFRt-expressing Tn/nem-enriched T cells after 28 days.
Receives: Biological: CD19CAR-CD28-CD3zeta-EGFRt-expressing Tn/mem-enriched T-lymphocytes; Other: Laboratory Biomarker Analysis

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Toxicity profile of T-cell infusion as defined by all toxicities associated with T cells at the probably or definite levels

    Assessed using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. The incidence of toxicity will also be measured according to the modified cytokine release syndrome grading as applicable. Tables will be created to summarize all toxicities and side effects by dose, time post treatment (first 28 days, days 29-60, 61-100, > 100), organ, severity, and attribution.

    Measured: Up to 15 years

  2. Dose-limiting toxicity (DLT) rate at the phase II recommended dose (RP2D) (CD19R(EQ)28zeta/EGFRt+ central memory T cells)

    Assessed using CTCAE version 4.0 for Arm I. Rates and associated 95% exact Clopper-Pearson binomial confidence limits will be estimated.

    Measured: Up to 28 days

  3. DLT rate at RP2D assessed using CTCAE version 4.0 for Arm II (CD19R(EQ)28zeta/EGFRt+ naive and memory T cells [TN/NEM])

    Rates and associated 95% exact Clopper-Pearson binomial confidence limits will be estimated.

    Measured: Up to 28 days

  4. Complete response (CR) or CR with incomplete bone marrow recovery (CRi) with the exception of participants in CR or CRi that go from minimal residual disease (MRD) negative to MRD positive or progress as determined by the principal investigator

    Rates and associated 95% exact Clopper-Pearson binomial confidence limits will be estimated.

    Measured: Within the first 28 days after infusion

Secondary outcomes (3)

  1. Detection of transferred T cells in the circulation for at least 28 days by quantitative-polymerase chain reaction (PCR)

    Rates and associated 95% exact Clopper-Pearson binomial confidence limits will be estimated.

    Measured: 28 days

  2. No MRD

    Rates and associated 95% exact Clopper-Pearson binomial confidence limits will be estimated. MRD over the study period will be reported using both descriptive statistics and graphical methods.

    Measured: Up to 15 years

  3. CD19 B cell aplasia/immunoglobulin G levels

    Normal CD19+ B cell levels over the study period will be reported using both descriptive statistics and graphical methods.

    Measured: Up to 12 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted26 May 2014 (estimated)
  2. Study start16 Oct 2014
  3. Primary completion17 Jun 2027 (estimated)
  4. Study completion17 Jun 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
71 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02146924
Sponsor's protocol ID
13447
Other IDs
NCI-2014-01060, 120202, 111660, 109630, 113660, 13447/115692, 118097, 13447
Status last verified
Aug 2026
First submitted
19 May 2014
Last updated
5 Aug 2026
Results posted
No
Data monitoring committee
Yes

Publications

  • Aldoss I, Goldberg L, Zhang J, Artz AS, Clark MC, Guan M, Espinosa R, Abimannan T, Wu J, Garcia B, Haas ER, Pathak KV, Lovell B, Pirrotte P, Agrawal V, Sanani N, Kasten S, Tilakawardane D, Wagner JR, Paul J, Shan H, Khaled S, Budde LE, Koller PB, Stein AS, Pullarkat VA, Salhotra A, Aribi A, Marcucci G, Wang X, Forman SJ. CAR T Cell Therapy as a Definitive Consolidation for Older Adults with B-ALL in First Complete Remission. Blood Adv. 2026 Jun 24:bloodadvances.2026020963. doi: 10.1182/bloodadvances.2026020963. Online ahead of print.

    PubMed 42341322

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing CD19CAR-CD28-CD3zeta-EGFRt-expressing Tcm-enriched T-lymphocytes, CD19CAR-CD28-CD3zeta-EGFRt-expressing Tn/mem-enriched T-lymphocytes and Laboratory Biomarker Analysis in people with B Acute Lymphoblastic Leukemia and Recurrent Acute Lymphoblastic Leukemia, run by City of Hope Medical Center at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 68 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 5 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Toxicity profile of T-cell infusion as defined by all toxicities associated with T cells at the probably or definite levels (time frame: Up to 15 years). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02146924, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Aug 2026.

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