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Acute Lymphocytic LeukemiaPhase 1NCT01430390

In Vitro Expanded Allogeneic Epstein-Barr Virus Specific Cytotoxic T-Lymphocytes (EBV-CTLs) Genetically Targeted to the CD19 Antigen in B-cell Malignancies

A Phase 1 study testing Biological/Genetically Modified T cells and Cyclophosphamide-based chemotherapy in people with Acute Lymphocytic Leukemia and Lymphoma, run by Memorial Sloan Kettering Cancer 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
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Trial summary

The purpose of this study is to test the safety of giving the patient special cells from a donor called "Modified T-cells". The goal is to assess the toxicities of T-cells for patients with relapsed B cell leukemia or lymphoma after a blood SCT organ SCT or for patients who are at high risk for relapse of their B cell… Read more about this study

Who is it for?
Any age
Conditions the study is for
Acute Lymphocytic Leukemia, Lymphoma
What is being tested?
Biological/Genetically Modified T cells and Cyclophosphamide-based chemotherapy
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
19 participants
Where
1 siteUnited States
Study dates
Sep 2011to Sep 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 Any age
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • History of CD19+ relapse/refractory (R/R) B cell malignancies occurring after allogeneic/autologous HSCT or solid organ transplant (SOT. (cohort 1)
  • Relapse on this protocol is detection of CD19+ malignancies in bone marrow morphology ≥ 5% any extramedullary lesion (radiographic), or detection of any disease level by cytogenetics, molecular, and/or flow cytometry.
  • History of relapsed or refractory CD19+ malignancies (e.g. Non Hodgkin Lymphoma) or considered high risk for relapse and and require autologous or allogeneic hematopoietic stem cell transplant (HSCT). Evidence of disease not required. (cohort 2 and 3)
  • No age restriction for patients
  • KPS or Lansky score > or = to 50
  • Renal function (measured prior to conditioning chemotherapy)
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  • Creatinine ≤ 2.0mg/dL for patients over 18 years of ≤ 2.5 x institutional ULN for age.
  • Hepatic function (measured prior to conditioning chemotherapy):
  • AST ≤ 5 x the institutional ULN Elevation secondary to leukemic involvement is not an exclusion criterion. Leukemic involvement will be determined by the presence of progressive relapse defined by escalating bone marrow or peripheral blood leukemia blasts within the previous month and the absence of initiation of know hepatotoxic medication (e.g. azoles).
  • Total bilirubin ≤ 2.5 x the institutional ULN
  • Adequate cardiac function (e.g. LVEF ≥ 40%) as assessed by ECHO or MUGA or other similar cardia imaging performed within 1 month of treatment.
  • Pulmonary function (measured prior to treatment):
  • Oxygen saturation ≥ 90% on room air
  • Donor Eligibility:
  • The patient's HSCT donor, or if HSCT donor is not available a third party donor, must consent to a leukapheresis or whole blood donation(s) obtained at one or more phlebotomies which, in aggregate, will total approximately 250 ml for adults and no more than 5ml/kg per draw from pediatric donors.
  • Related donors <18 years of age requiring placement of a leukapheresis catheter will donate peripheral blood collected by phlebotomy (including a unit of blood if weight permits) and shall not undergo catheter placement for leukapheresis as this is considered above minimal risk to the donor.
  • There is no upper age limit for a donors. However, the minimum age for a related donor is 7 years as this is the youngest age a person can be considered capable of giving assent to participate in a research study.
  • Evidence of prior sensitization to EBV by EBV serology testing (seropositive)
  • Donor's high resolution HLA typing must be available for review
  • CBC within one week of donation. Results of tests must be within a range that would not preclude donating blood or undergoing leukapheresis.
  • Serologic testing for transmissible diseases will be performed as per institutional guidelines adopted from extant NMDP and FACT guidelines. Donors should be considered eligible to donate leukapheresis or blood based on these guidelines (i.e. blood donation guidelines)

Who cannot join

  • Patients with active HIV, hepatitis B or hepatitis C infection.
  • Patients with any concurrent active malignancies as defined by malignancies requiring any therapy other than expectant observation.
  • Females who are pregnant.
  • Patients will be excluded if they have isolated extra-medullary relapse of ALL.
  • Patients with active (grade 2-4) acute graft versus host disease (GVHD), chronic GVHD or an overt autoimmune disease (e.g. hemolytic anemia) requiring glucocorticosteroid treatment (>0.5 mg/kg/day prednisone or its equivalent) as treatment
  • Active central nervous system (CNS) leukemia, as defined by unequivocal morphologic evidence of lymphoblasts in the cerebrospinal fluid (CSF) or symptomatic CNS leukemia (i.e. cranial nerve palsies or other significant neurologic dysfunction) within 28 days of treatment. Prophylactic intrathecal medication is not a reason for exclusion.
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  • Adult patients (≥18 years old) with the following cardiac conditions will be excluded:
  • New York Heart Association (NYHA) stage III or IV congestive heart failure
  • Myocardial infarction ≤ 6months prior to enrollment
  • History of clinically significant ventricular arrhythmia or unexplained syncope, not believed to be vasovagal in nature or due to dehydration.
  • History of severe non-ischemic cardiomyopathy with EF ≤20%
  • Uncontrolled, symptomatic, intercurrent illness including but not limited to infection, psychiatric illness, or social situations that would limit compliance with study requirements or in the opinion of the treating investigator would pose an unacceptable risk to the subject.
  • Prior irreversible neurologic toxicity to previous immunotherapy
  • Preceding and/or ongoing organ dysfunction or other co-morbidity including but not limited to uncontrolled infection that would impair the patient's ability to endure known side effects of cytokine release syndrome or neurological toxicity
  • Recent prior therapy: Systematic chemotherapy less than 2 weeks prior to infusion.
  • Recent prior therapy: Systematic chemotherapy less than 2 weeks prior to infusion. Exceptions:
  • There is no time restriction in regard to prior intrathecal chemotherapy provided tere is complete recovery from any acute toxic effects of such.
  • Subjects receiving hydroxyurea or oral maintenance chemotherapy may be enrolled provided there has been no increase in dose for at least 2 weeks prior to starting apheresis or treatment
  • Subjects receiving steroid therapy at physiological replacement doses only are allowed provided there has been no increase in dose for at least 2 weeks prior to subject starting apheresis or treatment.
  • Subjects must have recovered from the acute side effects of their prior therapy, such that eligibility criteria are met. Cytopenias deemed to be disease-related and not therapy-related are exempt from this exclusion.
  • Rapidly progressive disease that in the estimation of the treating physician would compromise ability to complete study therapy.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Memorial Sloan Kettering Cancer Center

    New York, New York, 10065

Other trials in United States

About this study

Official title: A Phase I Trial Using In Vitro Expanded Allogeneic Epstein-Barr Virus Specific Cytotoxic T-Lymphocytes (EBV-CTLs) Genetically Targeted to the CD19 Antigen in B-cell Malignancies

The purpose of this study is to test the safety of giving the patient special cells from a donor called "Modified T-cells". The goal is to assess the toxicities of T-cells for patients with relapsed B cell leukemia or lymphoma after a blood SCT organ SCT or for patients who are at high risk for relapse of their B cell leukemia or lymphoma.

Being tested
Biological/Genetically Modified T cells, Cyclophosphamide-based chemotherapy
Keywords
In Vitro Expanded Allogeneic Epstein-Barr Virus Specific Cytotoxic, T-Lymphocytes (EBV-CTLs), CD19 specific T-cells, 11-038
Medical subject headings
Precursor Cell Lymphoblastic Leukemia-Lymphoma, Lymphoma

What participants receive

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

  • Biological/Genetically Modified T cellsBiological

    Following completion of the chemotherapy, genetically modified T cells will be given intravenously at one of 3 dose levels. After the infusion patients will be monitored clinically and with serial blood and marrow evaluations to assess toxicity, therapeutic effects, and the in-vivo survival of the genetically modified T-cells. A fixed CAR EBV-CTL dose (3x106 EBV-CTLs/kg) which has been demonstrated to be the ideal manufacturing dose allowing for multiple infusions and potential for multiple patient treatments per cell line generated will be used for all patients on this trial. Cohorts will be determined separately but cohort 3 will not begin to accrue until cohort 2 has treated three (3) patients without a DLT. Each patient is eligible for up to three (3) infusions.

  • Cyclophosphamide-based chemotherapyDrug

    Cyclophosphamide-based chemotherapy regimen will be the preferred conditioning chemotherapy prior to CAR T cell infusion for patients with CD19+ malignancy in cohort 1. Recommended chemotherapy regimen consists of single agent Cyclophosphamide at a dose of 3000 mg/m2/dose IV over 1 hour or 1500mg/m2/dose x 2 doses given daily over 1 hour given for 2 days (patients may received reduced dose of cyclophosphamide based on the clinical status of the patient at discretion of the treating physician and with written approval by the MSKCC PI of this study). Alternative cyclophosphamide or non-cyclophosphamide-based regimens based on the clinical status of the patient, disease burden, and likely-hood of response may be used at the discretion of the treating physician with written approval by MSKCC PI of the study. Conditioning chemotherapy will not be given prior to infusions # 2 and #3.

Study groups in NCT01430390
Study groupRoleWhat they receive
Biological/Genetically Modified T cellsExperimentalUtilizing our initial trial experience, it was amended to include three (3) expansion cohorts. Cohort 1: patients with CD19+ relapse/refractory (R/R) B cell malignancies occurring after allogeneic/autologous HSCT or solid organ transplant (SOT) infusion occurring following conditioning chemotherapy. Cohort 2:patients with CD10+ high risk B cell malignancies eligible for autologous HSCT followed by 19-28z CRA EBV-CTLs (auto-HSCT preparative regimen serves as conditioning chemotherapy. Cohort 3: patients with CD19+ high risk B cell malignancies eligible for allogeneic HSCT followed by consolidative 19-28z CAR EBV-CTLs (allo-HSCT preparative regimen serves as conditioning chemotherapy) Each expansion cohort has a target accrual of 6 patients treated with fixed CAR EBV-CTL dose (3x106 EBV-CTLs/kg) which has been demonstrated to be the ideal manufacturing dose.
Receives: Biological: Biological/Genetically Modified T cells; Drug: Cyclophosphamide-based chemotherapy

What is being measured

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

  1. Evaluate the safety/persistence of (including GVHD) of allogeneic EBV specific CTL modified to express artificial T cell receptors targeting CD19 molecule given for persistence or relapse of B-Cell ALL post allogeneic HSCT.

    Measured: 3 years

Secondary outcomes (3)

  1. To assess the effects of the adoptively transferred CD19 specific T-cells on the progression of leukemia.

    Measured: 3 years

  2. To quantitate the number of chimeric antigen receptor (CAR) positive T-cells and donor EBV-CTL in the blood at defined intervals post infusion in order to determine their survival and proliferation in the host.

    Measured: 3 years

  3. To assess long-term status of treated patients

    Measured: 15 years

Timeline

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

  1. First posted8 Sep 2011 (estimated)
  2. Study startSep 2011
  3. Primary completionSep 2027 (estimated)
  4. Study completionSep 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
Not applicable
Intervention model
Single group
Model description
This is a phase I trial designed to identify tolerable and clinically active doses of allogeneic Epstein - Barr virus specific cytotoxic T lymphocytes (EBV-CTLs) genetically modified to target the B-cell antigen CD19 when administered to patients with CD19+
Masking
None (open label)
Enrolment
19 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01430390
Sponsor's protocol ID
11-038
Status last verified
Oct 2026
First submitted
6 Sep 2011
Last updated
6 Oct 2026
Results posted
No

Publications

  • Shahid S, Prockop SE, Flynn GC, Mauguen A, White CO, Bieler J, McAvoy D, Hosszu K, Cancio MI, Jakubowski AA, Scaradavou A, Boelens JJ, Sauter CS, Perales MA, Giralt SA, Taylor C, Chaudhari J, Wang X, Riviere I, Sadelain M, Brentjens RJ, Kernan NA, O'Reilly RJ, Curran KJ. Allogeneic off-the-shelf CAR T-cell therapy for relapsed or refractory B-cell malignancies. Blood Adv. 2025 Apr 8;9(7):1644-1657. doi: 10.1182/bloodadvances.2024015157.

    PubMed 39908482

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Biological/Genetically Modified T cells and Cyclophosphamide-based chemotherapy in people with Acute Lymphocytic Leukemia and Lymphoma, run by Memorial Sloan Kettering Cancer 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 21 inclusion and 21 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 6 Oct 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?

Evaluate the safety/persistence of (including GVHD) of allogeneic EBV specific CTL modified to express artificial T cell receptors targeting CD19 molecule given for persistence or relapse of B-Cell ALL post allogeneic HSCT. (time frame: 3 years). 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 NCT01430390, 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 6 Oct 2026.

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