Disease Stabilization in AML by Treatment With ATRA, Valproic Acid and Low-dose Cytarabine

This study has been completed.
Information provided by (Responsible Party):
Øystein Bruserud, University of Bergen
ClinicalTrials.gov Identifier:
First received: October 14, 2009
Last updated: June 23, 2015
Last verified: June 2015

Hypothesis: Combined treatment with valproic acid and ATRA can be used to achieve disease stabilization for a subset of patients with acute myelogenous leukemia (AML), and this effect can be improved without serious toxicity by adding low-dose cytarabine to this treatment.

Adult patients >18 years of age who can be included:

Elderly patients who cannot achieve standard chemotherapy, patients with relapsed or resistant AML.

Treatment: Combined therapy with:

Valproic acid, continuous therapy until disease progression ATRA, oral therapy for 14 days every three months Low-dose cytarabine 10 mg/m2 up to 10 injections during week 2 and 3, repeated every 3 months.

Condition Intervention Phase
Acute Myelogenous Leukemia
Drug: Cytarabine, all-trans retinoic acid, valproic acid
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Treatment of Acute Myelogenous Leukemia With the Histone Deacetylase Inhibitor Valproic Cid in Combination With All-trans Retinoic Acid (ATRA) and Low Dose Cytarabine

Resource links provided by NLM:

Further study details as provided by University of Bergen:

Primary Outcome Measures:
  • Survival [ Time Frame: 3 years ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Disease stabilization [ Time Frame: 3 years ] [ Designated as safety issue: Yes ]
  • Disease complications [ Time Frame: 3 years ] [ Designated as safety issue: Yes ]
  • Side effects of therapy [ Time Frame: 3 years ] [ Designated as safety issue: Yes ]

Enrollment: 36
Study Start Date: September 2009
Study Completion Date: June 2013
Primary Completion Date: February 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: ATRA+valproc acid+low-dose cytarabine Drug: Cytarabine, all-trans retinoic acid, valproic acid
ATRA: 22.5 mg/m2 twice daily for 2 weeks every third month Valproic acid: continuous therapy, dosage guided by serum levels Cytarabine: 10 mg/m2 once daily for up to 10 days every third month
Other Name: No other names

Detailed Description:

Patients to be included:

  1. Elderly patients (>60 years of age) or other patients unfit for conventional intensive chemotherapy with newly diagnosed acute myelogenous leukemia (AML).
  2. Adult patients of any age (>18 years of age) with relapsed or resistant AML who cannot receive conventional therapy.


Valproic acid to be started on day 1 as continuous therapy until disease progression.

ATRA administered from day 8 orally as 22.5 mg/m2 twice daily for 14 days, repeated every third month.

Low-dose cytarabine 10 mg/m2 from day 14 and continued as daily injections for up to 10 days, repeated every third month.

Supportive therapy is given according to the hospitals general guidelines.

Followup: The first 2 days treatment in hospital, later regular out-patient treatment. Controls will include clinical examination, peripheral blood parameters (including serum valproic acid levels), bone marrow samples.


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

Inclusion Criteria:

  • Recently diagnosed AML in patients unfit for intensive chemotherapy
  • Patients with relapsed or refractory AML

Exclusion Criteria:

  • No informed consent
  • Intolerance to study drugs
  • Serious liver disease
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00995332

Haukeland University Hospital and University of Bergen
Bergen, Norway, N-5021
Sponsors and Collaborators
University of Bergen
Study Chair: Oystein Bruserud, MD University of Bergen, Norway
  More Information

Responsible Party: Øystein Bruserud, Professor, University of Bergen
ClinicalTrials.gov Identifier: NCT00995332     History of Changes
Other Study ID Numbers: Rek VEST 231-06 
Study First Received: October 14, 2009
Last Updated: June 23, 2015
Health Authority: Norway: Norwegian Medicines Agency

Keywords provided by University of Bergen:
Acute myelogenous leukemia
all-trans retinoic acid
valproic acid
Disease stabilization

Additional relevant MeSH terms:
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Neoplasms by Histologic Type
Histone Deacetylase Inhibitors
Valproic Acid
Anti-Infective Agents
Antimanic Agents
Antimetabolites, Antineoplastic
Antineoplastic Agents
Antiviral Agents
Central Nervous System Agents
Central Nervous System Depressants
Dermatologic Agents
Enzyme Inhibitors
GABA Agents
Immunologic Factors
Immunosuppressive Agents
Keratolytic Agents
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Pharmacologic Actions
Physiological Effects of Drugs
Psychotropic Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on April 27, 2016