Description:
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.
Title
- Brief Title: 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)
Clinical Trial IDs
- ORG STUDY ID:
203835
- NCT ID:
NCT02124174
Conditions
- Acute Myelogenous Leukemia AML
- Myelodysplastic Syndrome MDS
Interventions
| Drug | Synonyms | Arms |
|---|
| Vidaza and Valproic Acid | Vidaza, Valproic Acid, Azacitadine | Vidaza and Valproic Acid |
Purpose
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
Trial Arms
| Name | Type | Description | Interventions |
|---|
| Vidaza and Valproic Acid | Experimental | Vidaza and Valproic Acid | |
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
| Maximum Eligible Age: | 89 Years |
| Minimum Eligible Age: | 2 Years |
| Eligible Gender: | All |
| Healthy Volunteers: | No |
Primary Outcome Measures
| Measure: | Survival |
| Time Frame: | 1 year |
| Safety Issue: | |
| Description: | Number of participants that survive post transplant for 1 year. |
Secondary Outcome Measures
| Measure: | Disease Relapse |
| Time Frame: | Day 0 to the day of first recurrance |
| Safety Issue: | |
| Description: | The time to relapse is from Day 0 to the day of first hematologic, cytogenetic, or radiological evidence of recurrent disease. |
Details
| Phase: | Phase 2 |
| Primary Purpose: | Interventional |
| Overall Status: | Recruiting |
| Lead Sponsor: | Patrick Stiff |
Trial Keywords
- acute myelogenous leukemia (AML)
- myelodysplastic syndrome (MDS)
Last Updated
April 26, 2021
