Clinical Trials /

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

NCT02124174

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.

Related Conditions:
  • Acute Myeloid Leukemia
  • Acute Myeloid Leukemia with t(8;21); (q22; q22.1); RUNX1-RUNX1T1
  • Acute Promyelocytic Leukemia
  • Core Binding Factor Acute Myeloid Leukemia
  • Myelodysplastic Syndromes
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

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

DrugSynonymsArms
Vidaza and Valproic AcidVidaza, Valproic Acid, AzacitadineVidaza 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

NameTypeDescriptionInterventions
Vidaza and Valproic AcidExperimentalVidaza and Valproic Acid
  • 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)

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