Clinical trial NCT02124174: Vidaza and Valproic Acid Post Allogeneic Transplant for High Risk AML and MDS
Official title: Maintenance Therapy With Azacitidine and Valproic Acid After Allogeneic Stem Cell Transplant in Patients With High-Risk Acute Myelogenous Leukemia (AML) or Myelodysplastic Syndrome (MDS)(Version 1_06 Jan 2012)
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Acute Myelogenous Leukemia AML
Myelodysplastic Syndrome MDS
Keywords: acute myelogenous leukemia (AML)
myelodysplastic syndrome (MDS)
Lead sponsor: Loyola University
Sponsor class: OTHER
First posted: 2014-04-28
Enrollment: 50
Sex: ALL
Minimum age (years): 2
Maximum age (years): 89
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Phase II trial combining azacitidine with valproic acid as maintenance therapy post allogeneic stem cell transplantation in patients with high-risk MDS/AML. We hypothesize that adding valproic acid to azacitidine will improve outcomes via both direct anti-tumor and immunologically mediated antitumor response with alloreactive donor lymphocytes, having an additive effect and extending 1 year survival in patient with high-risk AML/MDS after hematopoietic stem cell transplant. Based on aforementioned data from the US Department of Health and Human Services, standard 1 year survival for AML after stem cell transplant is near 40%. We hypothesize that valproic acid and azacitidine will prolong survival, with a 1 year survival goal of 60%. In addition to assessing for 1 year survival, we will have secondary objectives of assessing progression-free survival, relapse, and toxicity. The primary toxicity endpoint from this will be cytopenias and infections.

Detailed description: To assess the combination of valproic acid and azacitidine in preventing relapse in patients with high-risk Acute Myeloid Leukemia (AML) and myelodysplastic syndrome (MDS) after allogeneic stem cell transplant. The primary objective of this study will be determining the 1 year overall survival from combining valproic acid (VPA) with 5-azacytidine (5-aza).

To assess the effect that adding valproic acid to azacitidine will have in patient with high-risk Acute Myeloid Leukemia (AML) and myelodysplastic syndrome (MDS) after allogeneic stem cell transplant on the following endpoints

Eligibility criteria: Inclusion Criteria:

1. All allograft patients \> 2 years of age.
2. Patients will have one of the following malignancies:

   a. Patients with refractory or relapsed: acute myelogenous leukemia (AML) (including inv16, t(8;21) or t(15;17)) or high risk myelodysplastic syndrome (MDS) (defined as bone marrow blasts \> or = 5%) are eligible. Patients may be in remission at the time of entry.
3. Patients with adequate organ function and performance status criteria measured by:

   1. Karnofsky score greater than or equal to 70% or Performance status of \< or = 2 by the Eastern Cooperative Oncology Group (ECOG) scale
   2. Adequate liver function (bilirubin of \< 2mg/dL, serum glutamate pyruvate transaminase \< 3 \* ULN) and renal function (creatinine \< 2mg/dL)
4. Signed informed consent indicating that patients are aware of the investigational nature of this study in accordance with the regulations of Loyola University Medical Center
5. Patients must have undergone allogeneic stem cell transplant within 40-60 days before starting treatment and be self-sufficient in caloric intake along with no active graft vs. host disease

Exclusion Criteria:

1. Nursing and pregnant females are excluded.
2. Active and uncontrolled infections will cause patients to be excluded.
3. Patients already receiving valproic acid or receiving other anticonvulsants will be excluded.
4. Low risk AML in complete remission 1, will not be candidates for this study.
5. Patients with an absolute neutrophil count less than 1500 will be excluded
6. Patients with platelets less than 50,000 will be excluded
7. Children less than 2 years of age will be excluded due to increased hepatotoxicity from valproic acid in this age group

Primary outcomes:
measure: Survival
timeFrame: 1 year
Secondary outcomes:
measure: Disease Relapse
timeFrame: Day 0 to the day of first recurrance
Other outcomes:
Locations:
city: Maywood
country: United States
facility: Loyola University Cardinal Bernardin Cancer Center
state: Illinois
Study officials:
affiliation: Faculty
name: Patrick Stiff, MD
role: PRINCIPAL_INVESTIGATOR
References: