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

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2010 by University of Bergen
Sponsor:
Information provided by:
University of Bergen
ClinicalTrials.gov Identifier:
NCT00995332
First received: October 14, 2009
Last updated: June 9, 2011
Last verified: July 2010
  Purpose

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 ]

Estimated Enrollment: 25
Study Start Date: September 2009
Estimated Study Completion Date: January 2015
Estimated Primary Completion Date: December 2011 (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.

Treatment:

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.

  Eligibility

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

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
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: NCT00995332

Contacts
Contact: Oystein Bruserud, MD +47 55 97 29 97 oystein.bruserud@haukeland.no

Locations
Norway
Haukeland University Hospital and University of Bergen Recruiting
Bergen, Norway, N-5021
Contact: Oystein Bruserud, MD    +47 55 97 29 97    oystein.bruserud@haukeland.no   
Principal Investigator: Oystein Bruserud, MD         
Sponsors and Collaborators
University of Bergen
Investigators
Study Chair: Oystein Bruserud, MD University of Bergen, Norway
  More Information

No publications provided

Responsible Party: Professor Oystein Bruserud, University of Bergen and Haukeland University Hospital
ClinicalTrials.gov Identifier: NCT00995332     History of Changes
Other Study ID Numbers: Rek VEST 231-06
Study First Received: October 14, 2009
Last Updated: June 9, 2011
Health Authority: Norway: Norwegian Medicines Agency

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

Additional relevant MeSH terms:
Leukemia
Leukemia, Myeloid, Acute
Leukemia, Myeloid
Neoplasms by Histologic Type
Neoplasms
Valproic Acid
Cytarabine
Tretinoin
Histone Deacetylase Inhibitors
Anticonvulsants
Central Nervous System Agents
Therapeutic Uses
Pharmacologic Actions
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
Antimetabolites, Antineoplastic
Antimetabolites
Antineoplastic Agents
Antiviral Agents
Anti-Infective Agents
Immunosuppressive Agents
Immunologic Factors
Keratolytic Agents

ClinicalTrials.gov processed this record on August 28, 2014