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

NCT01483274 | Withdrawn Phase 1 DMC

• 1 other identifier: 13.0376
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Acute Myelogenous Leukemia

Keywords

AML; vaccine

Outcome Measures

Primary Outcomes (1)

• Tolerance of study treatment

  Tolerance to DAC, at least 50% dosing, and 3 of the 4 planned vaccinations during the first two cycles

  4 years

Secondary Outcomes (2)

• Disease Response

  4 years

• Immune Response

  4 years

Study Arms (2)

Safety

EXPERIMENTAL

Decitabine and donor lymphocyte infused dendritic cell (DC).

Biological: Vaccine

Vaccine

ACTIVE COMPARATOR

Decitabine and Dendritic cell (DC) pulsed with MAGE-A1, MAGE-A3, NY-ESO-1 Peptides

Biological: Vaccine

Interventions

Vaccine BIOLOGICAL

Decitabine followed by donor lymphocyte infusing and Dendritic cells pulsed with MAGE-A1, MAGE-A3, and NEY-ESO-1 vaccine

Also known as: DAC, Dendritic cells vaccine

Safety; Vaccine

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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:

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Louisville: lead

Study Sites (1)

University of Louisville

Louisville, Kentucky, 40202, United States

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

Vaccines

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Biological Products; Complex Mixtures

Study Officials

• Kenneth G Lucas, MD

  University of Louisville

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 3, 2011
• First Posted: December 1, 2011
• Study Start: March 1, 2015
• Primary Completion: June 1, 2015
• Study Completion: June 1, 2015
• Last Updated: May 9, 2017

Record last verified: 2017-05

Locations

US (1)