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

This study has been withdrawn prior to enrollment.
(PI transferred to University of Louisville)
Sponsor:
Collaborator:
Study was initiated at Penn State University, closed upon transfer of PI, and will be reopened at University of Louisville.
Information provided by (Responsible Party):
Kenneth Lucas, Penn State University
ClinicalTrials.gov Identifier:
NCT01483274
First received: November 3, 2011
Last updated: June 10, 2013
Last verified: June 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 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


Enrollment: 0
Study Start Date: June 2012
Study Completion Date: August 2012
Primary Completion Date: August 2012 (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 doner 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 doner 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:

  • Age 18 - 75 years
  • Histologically or cytologically documented relapse of acute myeloid leukemia after a stem cell transplant
  • Must have a minimum of 10% donor cells by chimerism assays (RFLP or FISH) prior to enrollment
  • Patients must be at least 2 weeks from cessation of immunosuppression.
  • Donors must be no more than two HLA antigen (HLA A, B, C, DR) mismatched with the transplant recipient by high resolution molecular HLA typing.
  • ECOG performance status 0-2, Lansky performance status >70 (see Appendix 1).
  • 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.

Exclusion Criteria:

  • Active CNS leukemia. Prior CNS leukemia allowed provided current CSF cytology is normal.
  • Current concomitant chemotherapy, radiation therapy, or immunotherapy. Must be off therapy for at least 2 weeks prior to enrollment with the following exceptions:
  • Hydroxyurea: at least 72 hours
  • Biologic agents (e.g., Imatinib, dasatinib, etc.): at least 7 days
  • Hematopoietic growth factors (e.g., filgrastim, pegfilgrastim, etc.): at least 7 days
  • Persistent clinically significant toxicity from prior anticancer therapy that is > Grade 2 (NCI CTCAE v3.0).
  • Bilirubin > 2 mg/dL, and SGOT/SGPT >2.5 x normal.
  • Ejection fraction by echocardiogram < 50%
  • Absolute neutrophil count < 500, platelet count < 25,000
  • Creatinine clearance < 50ml/min as estimated by patient's serum creatinine, weight, and age.
  • Room air pulse oximetry < 94%.
  • Bone marrow or stem cell transplant within 2 months prior to treatment on protocol
  • 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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01483274

Locations
United States, Pennsylvania
Penn State Hershey Medical Center
Hershey, Pennsylvania, United States, 17033
Sponsors and Collaborators
University of Louisville
Study was initiated at Penn State University, closed upon transfer of PI, and will be reopened at University of Louisville.
Investigators
Principal Investigator: Kenneth G Lucas, MD Penn State Hershey Medical Center
  More Information

No publications provided

Responsible Party: Kenneth Lucas, Professor of Pediatrics, Penn State University
ClinicalTrials.gov Identifier: NCT01483274     History of Changes
Other Study ID Numbers: 36361
Study First Received: November 3, 2011
Last Updated: June 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 June 18, 2013