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

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified April 2011 by Basque Health Service
Sponsor:
Information provided by:
Basque Health Service
ClinicalTrials.gov Identifier:
NCT01356875
First received: May 18, 2011
Last updated: May 19, 2011
Last verified: April 2011
  Purpose

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.


Condition Intervention Phase
Myelodysplastic Syndrome
Drug: BSC
Drug: HIDRA/VPA
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Basque Health Service:

Primary Outcome Measures:
  • change in hemoglobin from baseline in patients who express an erythroid response. [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
    Independence RBC transfusion requirement for ≥ 8 weeks (56 days) followed by treatment at any time.


Secondary Outcome Measures:
  • Erythroid response according to the criteria of the international working group of SMDs at 24 weeks [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
    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.


Estimated Enrollment: 42
Study Start Date: September 2011
Estimated Study Completion Date: January 2015
Estimated Primary Completion Date: September 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01356875

Contacts
Contact: Breno Moreno de Gusmao, MD +34-945 007000 breno.morenodegusmao@osakidetza.net

Locations
Spain
Txagorritxu Hospital Not yet recruiting
Vitoria-Gasteiz, Alava, Spain, 01009
Contact: Breno Moreno de Gusmao, MD    +34 945 007000    breno.morenodegusmao@osakidetza.net   
Sponsors and Collaborators
Basque Health Service
  More Information

No publications provided

Responsible Party: Breno Moreno De Gusmao, Osakidetza/Basque Health Service
ClinicalTrials.gov Identifier: NCT01356875     History of Changes
Other Study ID Numbers: SMD-TXAGO
Study First Received: May 18, 2011
Last Updated: May 19, 2011
Health Authority: Spain: Ethics Committee
Spain: Spanish Agency of Medicines

Keywords provided by Basque Health Service:
myelodysplastic syndrome
Transfusion
Hydralazine
valproic acid

Additional relevant MeSH terms:
Myelodysplastic Syndromes
Preleukemia
Syndrome
Bone Marrow Diseases
Disease
Hematologic Diseases
Neoplasms
Pathologic Processes
Precancerous Conditions
Hydralazine
Antihypertensive Agents
Cardiovascular Agents
Pharmacologic Actions
Therapeutic Uses
Vasodilator Agents

ClinicalTrials.gov processed this record on October 22, 2014