Differentiation Induction in Acute Myelogenous Leukemia - Full Text View

Sponsor:	University of Bergen
Information provided by:	University of Bergen
ClinicalTrials.gov Identifier:	NCT00175812

Purpose

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	Intervention	Phase
Acute Myelogenous Leukemia	Drug: all-trans retinoic acid (ATRA) Drug: Valproic acid Drug: Theophyllin	Phase I Phase II

Study Type:	Interventional
Study Design:	Treatment, Non-Randomized, Open Label, Uncontrolled, Single Group Assignment, Safety/Efficacy Study
Official Title:	Differentiation Induction Therapy for Acute Myelogenous Leukemia

Resource links provided by NLM:

MedlinePlus related topics: Leukemia, Adult Acute Leukemia, Adult Chronic

Drug Information available for: Theophylline Divalproex sodium Valproic acid Tretinoin Valproate Sodium Theophylline sodium glycinate

U.S. FDA Resources

Further study details as provided by University of Bergen:

Primary Outcome Measures:

Survival [ Time Frame: 2008 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Disease stabilisation [ Time Frame: 2008 ] [ Designated as safety issue: Yes ]
Disease complications [ Time Frame: 2008 ] [ Designated as safety issue: Yes ]
Side effects of therapy [ Time Frame: 2008 ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	30
Study Start Date:	November 2004
Estimated Study Completion Date:	November 2009
Primary Completion Date:	May 2008 (Final data collection date for primary outcome measure)

Intervention Details:

All-trans retinoic acid 22.5 mg/square meter twice daily days 1-14

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

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

Detailed Description:

Patients to be included:

Elderly patients above 60 years of age with newly diagnosed acute myelogenous leukemia (AML) who cannot receive conventional intensive chemotherapy.
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.

Treatment:

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.

Followup:

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.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	Yes

Criteria

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00175812

Locations

Norway
Haukeland University Hospital, University of Bergen
Bergen, Norway, N-5021

Sponsors and Collaborators

University of Bergen

Investigators

Principal Investigator:

Oystein Bruserud, MD

University of Bergen

More Information

Publications:

Raffoux E, Chaibi P, Dombret H, Degos L. Valproic acid and all-trans retinoic acid for the treatment of elderly patients with acute myeloid leukemia. Haematologica. 2005 Jul;90(7):986-8.

Trus MR, Yang L, Suarez Saiz F, Bordeleau L, Jurisica I, Minden MD. The histone deacetylase inhibitor valproic acid alters sensitivity towards all trans retinoic acid in acute myeloblastic leukemia cells. Leukemia. 2005 Jul;19(7):1161-8.

Pilatrino C, Cilloni D, Messa E, Morotti A, Giugliano E, Pautasso M, Familiari U, Cappia S, Pelicci PG, Lo Coco F, Saglio G, Guerrasio A. Increase in platelet count in older, poor-risk patients with acute myeloid leukemia or myelodysplastic syndrome treated with valproic acid and all-trans retinoic acid. Cancer. 2005 Jul 1;104(1):101-9.

Kuendgen A, Strupp C, Aivado M, Bernhardt A, Hildebrandt B, Haas R, Germing U, Gattermann N. Treatment of myelodysplastic syndromes with valproic acid alone or in combination with all-trans retinoic acid. Blood. 2004 Sep 1;104(5):1266-9. Epub 2004 May 20.

Additional publications automatically indexed to this study by National Clinical Trials Identifier (NCT ID):

Ryningen A, Stapnes C, Paulsen K, Lassalle P, Gjertsen BT, Bruserud O. In vivo biological effects of ATRA in the treatment of AML. Expert Opin Investig Drugs. 2008 Nov;17(11):1623-33.

Responsible Party:	Haukeland University Hospital ( Professor Øystein Bruserud )
Study ID Numbers:	REK-Vestnr21503
Study First Received:	September 9, 2005
Last Updated:	February 27, 2009
ClinicalTrials.gov Identifier:	NCT00175812 History of Changes
Health Authority:	Norway: Norwegian Medicines Agency

Keywords provided by University of Bergen:

Acute myelogenous leukemia
Differentiation
All trans retinoic acid
Valproic acid
Theophyllamin

Additional relevant MeSH terms:

Respiratory System Agents
Vasodilator Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Physiological Effects of Drugs
Psychotropic Drugs
Leukemia, Myeloid, Acute
Valproic Acid
Keratolytic Agents
Leukemia
Therapeutic Uses
Dermatologic Agents
Tranquilizing Agents
Neoplasms by Histologic Type

Central Nervous System Depressants
Anti-Asthmatic Agents
Enzyme Inhibitors
Cardiovascular Agents
Leukemia, Myeloid
Antimanic Agents
Pharmacologic Actions
Neoplasms
Phosphodiesterase Inhibitors
Autonomic Agents
Tretinoin
GABA Agents
Peripheral Nervous System Agents
Central Nervous System Agents
Bronchodilator Agents

ClinicalTrials.gov processed this record on November 27, 2009