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In Vitro Expanded Allogeneic Epstein-Barr Virus Specific Cytotoxic T-Lymphocytes (EBV-CTLs) Genetically Targeted to the B-Cell Specific Antigen CD19 Positive Residual Or Relapsed Acute Lymphoblastic Leukemia After Allogeneic Hematopoietic Progenitor Cell Transplantation

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2014 by Memorial Sloan-Kettering Cancer Center
Sponsor:
Collaborator:
Juno Therapeutics
Information provided by (Responsible Party):
Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier:
NCT01430390
First received: September 6, 2011
Last updated: August 26, 2014
Last verified: August 2014

September 6, 2011
August 26, 2014
September 2011
September 2015   (final data collection date for primary outcome measure)
Evaluate the safety/persistence of escalating doses 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 ] [ Designated as safety issue: Yes ]
toxicities [ Time Frame: 3 years ] [ Designated as safety issue: Yes ]
Toxicity will be graded on a scale of 1 to 5 as described by the NCI Common Terminology Criteria for Adverse Events (CTCAE), version 4.0. Assessment of toxicity will include assessment of the incidence and severity of Graft Versus Host Disease (GVHD) in treated patients since the development of GVHD may be a DLT.
Complete list of historical versions of study NCT01430390 on ClinicalTrials.gov Archive Site
  • To assess the effects of the adoptively transferred CD19 specific T-cells on the progression of leukemia. [ Time Frame: 3 years ] [ Designated as safety issue: No ]
  • To quantitate the number of chimeric antigen receptor (CAR) positive T-cells in the blood at defined intervals post infusion in order to determine their survival and proliferation in the host. [ Time Frame: 3 years ] [ Designated as safety issue: No ]
  • To assess long-term status of treated patients [ Time Frame: 15 years ] [ Designated as safety issue: No ]
  • effects of the adoptively transferred CD19 specific T-cells on the progression of leukemia. [ Time Frame: 3 years ] [ Designated as safety issue: No ]
    plan to record clinical leukemia responses as defined in Section 12.2 for descriptive analysis of the effects of the adoptively transferred CD19 specific T-cells on the progression of leukemia.
  • To quantitate the number of chimeric antigen receptor (CAR) positive T-cells in the blood [ Time Frame: 3 years ] [ Designated as safety issue: No ]
    at defined intervals post infusion in order to determine their survival and proliferation in the host.
  • long-term status [ Time Frame: 15 years ] [ Designated as safety issue: No ]
    patients will be followed annually for up to 15 years to assess long-term clinical status
Not Provided
Not Provided
 
In Vitro Expanded Allogeneic Epstein-Barr Virus Specific Cytotoxic T-Lymphocytes (EBV-CTLs) Genetically Targeted to the B-Cell Specific Antigen CD19 Positive Residual Or Relapsed Acute Lymphoblastic Leukemia After Allogeneic Hematopoietic Progenitor Cell Transplantation
A Phase I Dose Escalation Trial Using In Vitro Expanded Allogeneic Epstein-Barr Virus Specific Cytotoxic T-Lymphocytes (EBV-CTLs) Genetically Targeted to the B-Cell Specific Antigen CD19 Positive Residual Or Relapsed Acute Lymphoblastic Leukemia After Allogeneic Hematopoietic Progenitor Cell Transplantation

This Phase I dose escalation trial is designed to evaluate the safety and the biologic efficacy of allogeneic EBV specific cytotoxic T -lymphocytes (CTL) genetically modified to express artificial T-cell receptors (CAR) targeting the CD19 molecule (CD19CAR) in patients who have relapsed after allogeneic HSCT. Each patient will receive at least one dose of donor derived, genetically modified CTL and will be monitored for toxicity and detection of transduced CTL as well as disease specific markers.

Not Provided
Interventional
Phase 1
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Acute Lymphocytic Leukemia
Biological: Biological/Genetically Modified T cells
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.
Experimental: Biological/Genetically Modified T cells
Patients with persistent minimal residual disease (+MRD) or relapsed acute lymphoblastic leukemia following allogeneic hematopoietic progenitor cell transplantation will receive a conditioning chemotherapy regimen followed by intravenous infusion of allogeneic EBV specific cytotoxic T-cells (EBV-CTLs) genetically modified ex vivo to express the CD19-specific 19-28z chimeric artificial T-cell receptor.
Intervention: Biological: Biological/Genetically Modified T cells
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
26
September 2015
September 2015   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • History of CD19+ leukemia with evidence of bone marrow relapse or persistent MRD following allogenic hematopoietic stem cell transplantation.
  • Bone marrow relapse on this protocol is > 5% blasts by morphology and/or flow cytology.
  • Persistent minimal residual disease after transplantation must be demonstrated by morphology, FISH, flow cytometry or RT-PCR with at least 2 sequential testings separated by at least 1 week.
  • No age restriction for patients
  • KPS or Lansky score > or = to 40
  • Renal function (measured prior to conditioning chemotherapy)
  • 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 enrollment.
  • Pulmonary function (measured prior to conditioning chemotherapy):
  • 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)

Exclusion Criteria:

  • 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.
  • 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%
Both
Not Provided
No
Contact: Kevin Curran, MD 212-639-5836
Contact: Nancy Kernan, MD 212-639-7250
United States
 
NCT01430390
11-038
Not Provided
Memorial Sloan-Kettering Cancer Center
Memorial Sloan-Kettering Cancer Center
Juno Therapeutics
Principal Investigator: Kevin Curran, MD Memorial Sloan-Kettering Cancer Center
Memorial Sloan-Kettering Cancer Center
August 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP