Vidaza and Valproic Acid Post Allogeneic Transplant for High Risk AML and MDS

Sponsor

Patrick Stiff (Other)

Overall Status

Recruiting

CT.gov ID

NCT02124174

Collaborator

(none)

Enrollment

Location

Arm

120

Duration (Months)

0.4

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Acute Myelogenous Leukemia AML Myelodysplastic Syndrome MDS	Drug: Vidaza and Valproic Acid	Phase 2

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

Study Design

Study Type:

Interventional

Anticipated Enrollment :

50 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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 Start Date :

Jan 1, 2012

Anticipated Primary Completion Date :

Jan 1, 2022

Anticipated Study Completion Date :

Jan 1, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Vidaza and Valproic Acid Vidaza and Valproic Acid	Drug: Vidaza and Valproic Acid Days 1-5: 5-Azacytidine 40 mg/m^2 daily Days 1-5: +Valproic acid 15 mg/kg daily Days 6-28: Valproic acid 15 mg/kg daily *treatments will be repeated on the same days of each cycle for up to 4 total cycles. Each cycle will consist of 28 days. Other Names: Vidaza Valproic Acid Azacitadine

Arm

Intervention/Treatment

Experimental: Vidaza and Valproic Acid

Vidaza and Valproic Acid

Drug: Vidaza and Valproic Acid

Days 1-5: 5-Azacytidine 40 mg/m^2 daily Days 1-5: +Valproic acid 15 mg/kg daily Days 6-28: Valproic acid 15 mg/kg daily *treatments will be repeated on the same days of each cycle for up to 4 total cycles. Each cycle will consist of 28 days.

Other Names:

Vidaza

Valproic Acid

Azacitadine

Outcome Measures

Primary Outcome Measures

Survival [1 year]
Number of participants that survive post transplant for 1 year.

Secondary Outcome Measures

Disease Relapse [Day 0 to the day of first recurrance]
The time to relapse is from Day 0 to the day of first hematologic, cytogenetic, or radiological evidence of recurrent disease.

Eligibility Criteria

Criteria

Ages Eligible for Study:

2 Years to 89 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

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

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.

Patients with adequate organ function and performance status criteria measured by:
Karnofsky score greater than or equal to 70% or Performance status of < or = 2 by the Eastern Cooperative Oncology Group (ECOG) scale
Adequate liver function (bilirubin of < 2mg/dL, serum glutamate pyruvate transaminase < 3 * ULN) and renal function (creatinine < 2mg/dL)
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
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:

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