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

NCT01430390 | Active Not Recruiting Phase 1

• 1 other identifier: 11-038
• Study Type: interventional
• Target: 19
• Locations: 1 country
• Sites: 1

Brief 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 leukemia or lymphoma.

Conditions

Acute Lymphocytic Leukemia; Lymphoma

Keywords

In Vitro Expanded Allogeneic Epstein-Barr Virus Specific Cytotoxic; T-Lymphocytes (EBV-CTLs); CD19 specific T-cells; 11-038

Outcome Measures

Primary Outcomes (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.

  3 years

Secondary Outcomes (3)

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

  3 years

• 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.

  3 years

• To assess long-term status of treated patients

  15 years

Study Arms (1)

Biological/Genetically Modified T cells

EXPERIMENTAL

Utilizing 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.

Biological: Biological/Genetically Modified T cells; Drug: Cyclophosphamide-based chemotherapy

Interventions

Biological/Genetically Modified T cells BIOLOGICAL

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.

Biological/Genetically Modified T cells

Cyclophosphamide-based chemotherapy DRUG

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.

Biological/Genetically Modified T cells

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)
• Creatinine ≤ 2.0mg/dL for patients over 18 years of ≤ 2.5 x institutional ULN for age.
• Hepatic function (measured prior to conditioning chemotherapy):
• 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.

You may not qualify if:

• 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
• 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:

Sponsors & Collaborators

• Memorial Sloan Kettering Cancer Center: lead

Study Sites (1)

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Related Publications (1)

• 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.

  PMID: 39908482 DERIVED

Related Links

• Memorial Sloan Kettering Cancer Center

MeSH Terms

Conditions

Precursor Cell Lymphoblastic Leukemia-Lymphoma; Lymphoma

Interventions

Biological Products

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

Intervention Hierarchy (Ancestors)

Complex Mixtures

Study Officials

• Kevin Curran, MD

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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+

Study Record Dates

• First Submitted: September 6, 2011
• First Posted: September 8, 2011
• Study Start: September 1, 2011
• Primary Completion (Estimated): September 1, 2026
• Study Completion (Estimated): September 1, 2026
• Last Updated: June 11, 2025

Record last verified: 2025-06

Locations

US (1)