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Differentiation Induction in Acute Myelogenous Leukemia

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00175812
Recruitment Status : Completed
First Posted : September 15, 2005
Last Update Posted : June 24, 2015
Information provided by (Responsible Party):
Øystein Bruserud, University of Bergen

Brief Summary:

Hypothesis: Differentiation induction therapy in acute myelogenous leukemia (AML) can be used to achieve disease control and stabilize peripheral blood counts in patients with acute myelogenous leukemia.

Adult patients (<18 years of age) who can be included: Elderly patients (>60 years of age) with newly diagnosed AML who cannot achieve standard chemotherapy, patients with relapsed or resistant AML. Patients with relapsed or resistant AML who cannot receive intensive chemotherapy.

Treatment: Patients will be treated with all-trans retinoic acid (oral administration), valproic acid (7 days intravenous administration and later oral administration)and theophyllamine (7 days intravenous administration and later oral administration). Duration of treatment at least 2 months or until disease progression. Maximal duration of treatment 2 years.

Followup: Clinical evaluation, peripheral blood samples, bone marrow samples.

Condition or disease Intervention/treatment Phase
Acute Myelogenous Leukemia Drug: all-trans retinoic acid (ATRA) Drug: Valproic acid Drug: Theophyllin Phase 1 Phase 2

Detailed Description:

Patients to be included:

  1. Elderly patients above 60 years of age with newly diagnosed acute myelogenous leukemia (AML) who cannot receive conventional intensive chemotherapy.
  2. Adult patients of any age (> 18 years of age)with relapsed or resistant AML who cannot receive conventional intensive chemotherapy or allogeneic stem cell transplantation.

We plan to include at least 20 patients, but if possible 30 patients during a 3 years period. The first patient was included November 2004.


All-trans retinoic acid (ATRA) administered orally 22.5 mg/m2 twice daily for 14 days, repeated every third month.

Valproic acid started on day 3 of ATRA therapy, the first week as intravenous administration and later oral administration.

Theophyllamine started on day 3 of ATRA therapy, the first week as intravenous administration and later oral administration.

Duration of treatment at least 2 months unless side effects,until disease progression or an overall duration of treatment of 2 years.

Supportive therapy according to the hospitals general guidelines.


The first week treatment in hospital. Later out-patient treatment with regular controls including clinical examination, peripheral blood parameters (including serum valproic acid and theophyllamin levels), bone marrow samples.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 24 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Differentiation Induction Therapy for Acute Myelogenous Leukemia
Study Start Date : November 2004
Actual Primary Completion Date : May 2008
Actual Study Completion Date : November 2009

Arm Intervention/treatment
Experimental: ATRA plus valproic acid plus theophyllin
ATRA for 14 days, continuous treatment with valproic acid and theophyllin
Drug: all-trans retinoic acid (ATRA)
All-trans retinoic acid 22.5 mg/square meter twice daily days 1-14

Drug: Valproic acid
Valproic acid, highest dose without side effects from day 3 until progression

Drug: Theophyllin
Theophyllin, targetted serum level 50-100 from day 3 until progression

Primary Outcome Measures :
  1. Survival [ Time Frame: 2008 ]

Secondary Outcome Measures :
  1. Disease stabilisation [ Time Frame: 2008 ]
  2. Disease complications [ Time Frame: 2008 ]
  3. Side effects of therapy [ Time Frame: 2008 ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes

Inclusion Criteria:

  • Recently diagnosed acute myelogenous leukemia (AML)
  • Patients above 60 years of age
  • Patients who cannot receive conventional chemotherapy
  • Patients with relapsed or refractory AML independent of age

Exclusion Criteria:

  • Chronic myelogenous leukemia in blast phase
  • Intolerance to the study drugs
  • Serious liver disease
  • No informed consent

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00175812

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Haukeland University Hospital, University of Bergen
Bergen, Norway, N-5021
Sponsors and Collaborators
University of Bergen
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Principal Investigator: Oystein Bruserud, MD University of Bergen
Publications of Results:
Publications automatically indexed to this study by Identifier (NCT Number):
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Responsible Party: Øystein Bruserud, Professor, University of Bergen Identifier: NCT00175812    
Other Study ID Numbers: REK-Vestnr21503
First Posted: September 15, 2005    Key Record Dates
Last Update Posted: June 24, 2015
Last Verified: June 2015
Keywords provided by Øystein Bruserud, University of Bergen:
Acute myelogenous leukemia
All trans retinoic acid
Valproic acid
Additional relevant MeSH terms:
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Leukemia, Myeloid
Leukemia, Myeloid, Acute
Neoplasms by Histologic Type
Valproic Acid
Antineoplastic Agents
Keratolytic Agents
Dermatologic Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
GABA Agents
Neurotransmitter Agents
Physiological Effects of Drugs
Antimanic Agents
Tranquilizing Agents
Central Nervous System Depressants
Psychotropic Drugs
Bronchodilator Agents
Autonomic Agents
Peripheral Nervous System Agents
Anti-Asthmatic Agents
Respiratory System Agents
Phosphodiesterase Inhibitors
Vasodilator Agents
Purinergic P1 Receptor Antagonists
Purinergic Antagonists