Decitabine and Vaccine Therapy for Patients With Relapsed AML Following Allogeneic Stem Cell Transplantation

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified December 2013 by University of Louisville
Sponsor:
Information provided by (Responsible Party):
Kenneth Lucas, University of Louisville
ClinicalTrials.gov Identifier:
NCT01483274
First received: November 3, 2011
Last updated: December 10, 2013
Last verified: December 2013
  Purpose

Patients with Acute Myelogenous Leukemia (AML) who relapse after an allogeneic stem cell transplant cell receive decitabine to up regulate cancer antigen expression, followed by a donor lymphocyte infusion and an autologous dendritic cell (DC). Vaccine Dendritic cells are pulsed with overlapping peptides derived from MAGE-A1, MAGE-A3, and NY-ESO-1.


Condition Intervention Phase
Acute Myelogenous Leukemia
Biological: Vaccine
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Pharmacologic Upregulation of Cancer Testis Antigens Followed by Vaccine Therapy for Patients With Relapsed Acute Myelogenous Leukemia (AML) Following Allogeneic Stem Cell Transplantation

Resource links provided by NLM:


Further study details as provided by University of Louisville:

Primary Outcome Measures:
  • Tolerance of study treatment [ Time Frame: 4 years ] [ Designated as safety issue: Yes ]
    Tolerance to DAC, at least 50% dosing, and 3 of the 4 planned vaccinations during the first two cycles


Secondary Outcome Measures:
  • Disease Response [ Time Frame: 4 years ] [ Designated as safety issue: No ]
    Assessment of Bone Marrow aspiration to check for complete or partial remission, stable disease, and disease progression by bone marrow draws at week 6 and week 12.

  • Immune Response [ Time Frame: 4 years ] [ Designated as safety issue: No ]
    Assessment of post-vaccination T cell responses to MAGE-A1, MAGE-A3, and NY-ESO-1 by immunoassay


Estimated Enrollment: 10
Study Start Date: February 2014
Estimated Study Completion Date: January 2015
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Safety
Decitabine and donor lymphocyte infused dendritic cell (DC).
Biological: Vaccine
Decitabine followed by donor lymphocyte infusing and Dendritic cells pulsed with MAGE-A1, MAGE-A3, and NEY-ESO-1 vaccine
Other Names:
  • DAC
  • Vaccine
  • Dendritic cells vaccine
Active Comparator: Vaccine
Decitabine and Dendritic cell (DC) pulsed with MAGE-A1, MAGE-A3, NY-ESO-1 Peptides
Biological: Vaccine
Decitabine followed by donor lymphocyte infusing and Dendritic cells pulsed with MAGE-A1, MAGE-A3, and NEY-ESO-1 vaccine
Other Names:
  • DAC
  • Vaccine
  • Dendritic cells vaccine

Detailed Description:

For vaccine production, mature DC will be pulsed with overlapping peptides mixes derived from full-length NY-ESO-1, MAGE-A1, and MAGE-A3.

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria for study enrollment:

  • Signed informed consent after discussion of alternative therapies.
  • The first six patients be18 to 65 years old. Patients # 7-10 will range in age from 2 - 65 years.
  • Histologically or cytogenetically confirmed diagnosis of acute myelogenous leukemia prior to allogeneic SCT, with the following risk factors:

    • > second complete response, or in relapse, at the time of transplant
    • monosomy 5 or 7
    • the presence of a high FLT3/ITD allelic ratio
    • patients with detectable minimal residual disease (MRD) post-transplant
    • < 0.5% positive for recipient leukemia cells by flow cytometry

Inclusion criteria to begin study therapy:

  • Patient is at least three months post-transplant.
  • Patients must be off systemic immunosuppression for at least two weeks prior to the start of therapy on the study.
  • ECOG performance status 0-2, Lansky performance status >70 (see Appendix 1).
  • Hematologic Function: ANC: ≥ 500; Platelet count: ≥ 75.
  • Renal Function:

    • Creatinine clearance or radioisotope GFR ≥ 70ml/min/1.73 m2 OR a serum creatinine based on age/gender using the Schwartz formula:
  • Cardiac Function: Patient must have normal cardiac function documented within two weeks before starting of a treatment cycle 1 by:

    • Ejection fraction (> 55%) documented by echocardiogram or fractional shortening (≥ 28%) documented by echocardiogram.
  • Liver Function: Total bilirubin ≤ 1.5 x normal for age, and ALT (SGPT) and AST (SGOT) ≤ 3 x normal for age.
  • Room air pulse oximetry > 94%.
  • Female patients of childbearing potential must have a negative serum pregnancy test within 7 days of enrollment.
  • Male and female patients must agree to use a medically acceptable barrier and/or chemical contraceptive method during the study and for a minimum of 3 months after the last dose of chemotherapy on this study.
  • Subjects must be > 3 months and < 12 months post-SCT at the time of the first vaccination.
  • Donor chimerism must be > 90%, assist at least two weeks prior to beginning treatment
  • Subjects must be at least 30 days post-transplant to enroll on the study and to undergo apheresis, and must be at least three months post-transplant to begin therapy with DAC/vaccine.
  • Stem cell donor source may be related or unrelated donor cord blood, related or unrelated donor bone marrow, and related or unrelated donor peripheral blood stem cell product. Donors may be no more than two HLA (A, B, C, DR, DQ) antigen mismatched with the recipient.

Exclusion Criteria:

  • Patient has a history of autoimmune disease, specifically inflammatory bowel disease, systemic lupus erythematosis, or rheumatoid arthritis.
  • Patient has a known systemic hypersensitivity to DAC, imiquimod, or any vaccine component.
  • Patient has evidence of recurrent leukemia.
  • Patient is receiving systemic corticosteroids or other immunosuppression.
  • Persistent clinically significant toxicity from prior anticancer therapy that is > Grade 2 (NCI CTCAE v3.0).
  • Pregnant or lactating females are excluded.
  • Other active systemic malignancy other than leukemia expected to require therapy within 4 months.
  • Patients with a systemic fungal, bacterial, viral, or other infection not controlled (defined as exhibiting ongoing signs/symptoms related to the infection and without improvement, despite appropriate antibiotics or other treatment).
  • Any condition which, in the opinion of the investigator, would compromise patient safety or compliance, interfere with consent, study participation, follow up, or interpretation of study results.
  • Patients with a positive result for any of the following diagnostic tests: Hep B Ag, Hep B Core Ab, Hep C Ab, HIV-1 Ab, HIV-2 Ab, HTLV-1 Ab, HTLV-2 Ab, RPR.
  • Received any investigational new drug within 30 days prior to the first dose of vaccine , or are scheduled to receive an investigational new during the course of the study
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01483274

Contacts
Contact: Kenneth G Lucas, MD 502-852-8450 k0luca01@louisville.edu
Contact: Lisa A Good 502-629-5874 lagood06@louisville.edu

Locations
United States, Kentucky
University of Louisville Not yet recruiting
Louisville, Kentucky, United States, 40202
Contact: Kenneth G Lucas, MD    502-852-8450    k0luca01@louisville.edu   
Contact: Lisa A Good    502-629-5874    lagood06@louisville.edu   
Principal Investigator: Kenneth G Lucas, MD         
Sponsors and Collaborators
University of Louisville
Investigators
Principal Investigator: Kenneth G Lucas, MD University of Louisville
  More Information

No publications provided

Responsible Party: Kenneth Lucas, Professor of Pediatrics, University of Louisville
ClinicalTrials.gov Identifier: NCT01483274     History of Changes
Other Study ID Numbers: 13.0376
Study First Received: November 3, 2011
Last Updated: December 10, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by University of Louisville:
AML
vaccine

Additional relevant MeSH terms:
Leukemia
Leukemia, Myeloid, Acute
Leukemia, Myeloid
Neoplasms by Histologic Type
Neoplasms
Decitabine
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Enzyme Inhibitors

ClinicalTrials.gov processed this record on July 24, 2014