Treatment of Myelodysplastic Syndromes Comparing Hydralazine/Ac. Valproic and Supportive Care in Patients Not Candidates, Refractory and/or Intolerant to Intensive Chemotherapy

Phase II Clinical Trial for Treatment of Myelodysplastic Syndromes Comparing Hydralazine / Ac.Valproico and Supportive Care in Patients Not Candidates, Refractory and / or Intolerant to Intensive Chemotherapy

Transfusional dependence has been associated closely and independently with low survival in patients with myelodysplastic syndrome (MDS), especially in patients at low risk according to IPSS. Treatment of patients with hydralazine + valproic acid as an alternative to treatment with 5-azacytidine has lower cost and possibly as effective with fewer side effects. The objective of this phase II study is to determine the effectiveness of combination therapy with hydralazine + Ac. Valproic compared with best supportive care. The investigators will select 42 patients per group, and after 14 weeks of treatment the investigators will study in both groups the hematological response (transfusion-dependent, hemoglobin, cytogenetics and morphology) and treatment safety (adverse reactions and vital signs) to 1 year after starting treatment. The concentration of hemoglobin, the number of transfusions, platelets, neutrophils and other continuous variables in both groups will be compared by Student t or Mann-Whitney, as appropriate. For comparison of cytogenetic and morphological response and other categorical variables between groups Chi square will be used. And within each group the investigators will compare each of these variables before and after treatment by t-test for paired data or Wilcoxon test.

Study Overview

• Status: Unknown
• Conditions: Myelodysplastic Syndrome
• Intervention / Treatment: Drug: HIDRA/VPA; Drug: BSC

• Study Type: Interventional
• Enrollment (Anticipated): 42
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Breno Moreno de Gusmao, MD; Phone Number: +34-945 007000; Email: breno.morenodegusmao@osakidetza.net

Study Locations

• Spain
  • Alava
    • Vitoria-Gasteiz, Alava, Spain, 01009
      • Txagorritxu Hospital
      • Contact: Breno Moreno de Gusmao, MD; Phone Number: +34 945 007000; Email: breno.morenodegusmao@osakidetza.net

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Ability to understand and voluntarily sign the consent form.
2. Age ≥ 18 years at the time of signing the informed consent form.
3. Ability and willingness to meet the schedule of study visits and other protocol requirements.
4. Documented diagnosis of SMDs according to the criteria of disease risk IPSS intermediate-2, high risk or any risk with transfusion requirements.
5. Transfusion-dependent anemia erythrocytes defined as the absence of a period of 56 consecutive days without transfusion of red blood cells for at least 112 days prior (16 weeks).
6. Engage both women and men to use highly effective contraception.
7. Patients are not candidates for treatment with azacitidine or chemotherapy

Exclusion Criteria:

• Patients who have any of these exclusion criteria may not be included in the trial:

  1. Pregnant or breastfeeding.
  2. After hematopoietic stem cell transplantation.
  3. Patients with vitamin B12 deficiency, Folic Acid and Iron
  4. Any severe psychiatric illness or condition that prevents the patient sign the consent form for the patient or involves an unacceptable risk in case of participating in the study.
  5. Hypersensitivity to hydralazine and / or AC. Valproic

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: HIDRA/VPA; In each cycle (30 days), Hydralazine 50mg tablets every 12 hours and Valproic 500mg tablets every 8 hours will be administrated orally to HYDRA / VPA group.Each patient will receive 6 cycles of hydralazine and valproic acid.	Drug: HIDRA/VPA; In each cycle (30 days), Hydralazine 50mg tablets every 12 hours and Valproic 500mg tablets every 8 hours will be administrated orally to HYDRA / VPA group.Each patient will receive 6 cycle.
Active Comparator: best supportive care (BSC); The support group will be receive transfusional BSC, erythropoietin and / or G-CSF as determined by the physician.	Drug: BSC; The support group will be receive transfusional BSC, erythropoietin and / or G-CSF as determined by the physician.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
change in hemoglobin from baseline in patients who express an erythroid response.	Independence RBC transfusion requirement for ≥ 8 weeks (56 days) followed by treatment at any time.	8 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Erythroid response according to the criteria of the international working group of SMDs at 24 weeks	Number and type of administered blood transfusions, time between the last transfusion prior to inclusion in the study and the first transfusion after the 8 weeks of treatment.	24 weeks

Collaborators and Investigators

• Sponsor: Basque Health Service

Study record dates

Study Major Dates

• Study Start: September 1, 2011
• Primary Completion (Anticipated): September 1, 2014
• Study Completion (Anticipated): January 1, 2015

Study Registration Dates

• First Submitted: May 18, 2011
• First Submitted That Met QC Criteria: May 19, 2011
• First Posted (Estimate): May 20, 2011

Study Record Updates

• Last Update Posted (Estimate): May 20, 2011
• Last Update Submitted That Met QC Criteria: May 19, 2011
• Last Verified: April 1, 2011

More Information

Terms related to this study

• Keywords: Transfusion; myelodysplastic syndrome; valproic acid; Hydralazine
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Disease; Bone Marrow Diseases; Hematologic Diseases; Precancerous Conditions; Syndrome; Myelodysplastic Syndromes; Preleukemia
• Other Study ID Numbers: SMD-TXAGO