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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

November 3, 2011
December 10, 2013
February 2014
December 2014   (final data collection date for primary outcome measure)
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
Same as current
Complete list of historical versions of study NCT01483274 on ClinicalTrials.gov Archive Site
  • 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
  • Disease Responce [ Time Frame: 4 years ] [ Designated as safety issue: No ]
    Assessment of Bone Marrow asperation to check for complete or partial remission, stable disease, and desease prgression by bone marrow draws at week 6 and week 12.
  • Immune Responce [ 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
Not Provided
Not Provided
 
Decitabine and Vaccine Therapy for Patients With Relapsed AML Following Allogeneic Stem Cell Transplantation
Pharmacologic Upregulation of Cancer Testis Antigens Followed by Vaccine Therapy for Patients With Relapsed Acute Myelogenous Leukemia (AML) Following Allogeneic Stem Cell Transplantation

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.

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

Interventional
Phase 1
Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Acute Myelogenous Leukemia
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
  • Experimental: Safety
    Decitabine and donor lymphocyte infused dendritic cell (DC).
    Intervention: Biological: Vaccine
  • Active Comparator: Vaccine
    Decitabine and Dendritic cell (DC) pulsed with MAGE-A1, MAGE-A3, NY-ESO-1 Peptides
    Intervention: Biological: Vaccine
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Not yet recruiting
10
January 2015
December 2014   (final data collection date for primary outcome measure)

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
Both
18 Years to 75 Years
No
Contact: Kenneth G Lucas, MD 502-852-8450 k0luca01@louisville.edu
Contact: Lisa A Good 502-629-5874 lagood06@louisville.edu
United States
 
NCT01483274
13.0376
Yes
Kenneth Lucas, University of Louisville
University of Louisville
Not Provided
Principal Investigator: Kenneth G Lucas, MD University of Louisville
University of Louisville
December 2013

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