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 April 2014 by Memorial Sloan-Kettering Cancer Center
Sponsor:
Information provided by (Responsible Party):
Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier:
NCT01430390
First received: September 6, 2011
Last updated: April 30, 2014
Last verified: April 2014

September 6, 2011
April 30, 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
Allocation: Non-Randomized
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
During the dose escalation phase three patients will be entered at each dose level (depending on toxicity). If there are no toxicities and immunological efficacy is not seen at any dose, the doses will be further escalated. Upon completion of dose escalation we will treat a maximum of 14 patients at the highest dose.
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:

  • Patients treated on this protocol will have been diagnosed with CD19+ leukemia at less than 19 years of age.
  • History of CD19+ leukemia with evidence of bone marrow relapse or persistent MRD following allogenic hematopoietic stem cell transplantation.
  • Persistent minimal residual disease after transplantation must be demonstrated by morphology, karyotype, FSH, flow cytometry or RT-PCR with at least 2 sequential testings separated by at least 1 week.
  • We expect that there will be cases in which a patient will experience a leukemia relapse and will require chemotherapy during the establishment, expansion and modification of EBV-CTLs. The timeline for establishing the EBV-BLCL (3-5 weeks), establishing EBV specific T-cell line (6-8 weeks) and expanding the genetically modified EBV specific T-cell line (1-4 weeks) is considerable. During this time patients may receive chemotherapy at the discretion of their treating physician. If the patient receives chemotherapy they must have recovered from any chemotherapy induced toxicity and meet all eligibility criteria for organ function for this protocol at the time the conditioning therapy is initiated. If the patient has been rendered hypoplastic by the chemotherapy, the patient may proceed to T-cell therapy with conditioning therapy prior to the resurgence of a blastic marrow.
  • The patient's hematopoietic stem cell transplant donor must consent to a leukapheresis or whole blood donations 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 under the age of 18 will donate peripheral blood collected by phlebotomy (including a unit of blood if weight permits) and shall not undergo leukopheresis which is considered above minimal risk to the donor.
  • Unrelated volunteer donors should be between the age if 18 and 60 years as these are the age restrictions for volunteer unrelated donor registries. There is no upper age limit for a related donor. 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.
  • Organ Function as determined on the day of initiation of lymphodepleting cytoreduction.

    1. KPS or Lansky score > 30
    2. Renal function at the time of treatment: Creatinine ≤2.0mg/dL
    3. Hepatic function at time of treatment: AST ≤ 3.0 x the institutional ULN, total bilirubin ≤ 2.5 x the institutional ULN
    4. Pulmonary function: Oxygen saturation ≥ 90% on room air
  • Patients treated on this protocol will have been diagnosed with CD19+ leukemia at less than 19 years of age.
  • Patients with CNS relapse are eligible. However, if patient receives intrathecal chemotherapy, at least 24 hours must elapse prior to the T-cell infusion.

Exclusion Criteria:

  • 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.
  • Patients with other life-threatening conditions not related to leukemia (e.g. veno-occlusive disease or uncontrolled bacterial, viral or invasive fungal infection) which would confound evaluation of the effects of an infusion of genetically modified T-cells.
  • Females who are pregnant.
  • Patient or guardian is unable to give informed consent or unable to comply with the treatment protocol including appropriate supportive care, follow-up, and research tests.
Both
up to 19 Years
No
Contact: Nancy Kernan, MD 212-639-7250
Contact: Renier Brentjens, MD, PhD 212-639-7053
United States
 
NCT01430390
11-038
Not Provided
Memorial Sloan-Kettering Cancer Center
Memorial Sloan-Kettering Cancer Center
Not Provided
Principal Investigator: Nancy Kernan, MD Memorial Sloan-Kettering Cancer Center
Memorial Sloan-Kettering Cancer Center
April 2014

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