Clinical trial NCT01483274: Decitabine and Vaccine Therapy for Patients With Relapsed AML Following Allogeneic Stem Cell Transplantation
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
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE1
Conditions: Acute Myelogenous Leukemia
Keywords: AML
vaccine
Lead sponsor: University of Louisville
Sponsor class: OTHER
First posted: 2011-12-01
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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 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

Primary outcomes:
measure: Tolerance of study treatment
timeFrame: 4 years
Secondary outcomes:
measure: Disease Response
timeFrame: 4 years
measure: Immune Response
timeFrame: 4 years
Other outcomes:
Locations:
city: Louisville
country: United States
facility: University of Louisville
state: Kentucky
Study officials:
affiliation: University of Louisville
name: Kenneth G Lucas, MD
role: PRINCIPAL_INVESTIGATOR
References: