Differentiation Induction in Acute Myelogenous Leukemia
Differentiation Induction Therapy for Acute Myelogenous Leukemia
1 other identifier
interventional
24
1 country
1
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_1
Started Nov 2004
Longer than P75 for phase_1
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
Study Start
First participant enrolled
November 1, 2004
CompletedFirst Submitted
Initial submission to the registry
September 9, 2005
CompletedFirst Posted
Study publicly available on registry
September 15, 2005
CompletedPrimary Completion
Last participant's last visit for primary outcome
May 1, 2008
CompletedStudy Completion
Last participant's last visit for all outcomes
November 1, 2009
CompletedJune 24, 2015
June 1, 2015
3.5 years
September 9, 2005
June 23, 2015
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Survival
2008
Secondary Outcomes (3)
Disease stabilisation
2008
Disease complications
2008
Side effects of therapy
2008
Study Arms (1)
ATRA plus valproic acid plus theophyllin
EXPERIMENTALATRA for 14 days, continuous treatment with valproic acid and theophyllin
Interventions
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
Eligibility Criteria
You may qualify if:
- 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
You may not qualify if:
- Chronic myelogenous leukemia in blast phase
- Intolerance to the study drugs
- Serious liver disease
- No informed consent
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
Haukeland University Hospital, University of Bergen
Bergen, N-5021, Norway
Related Publications (5)
Ryningen A, Stapnes C, Lassalle P, Corbascio M, Gjertsen BT, Bruserud O. A subset of patients with high-risk acute myelogenous leukemia shows improved peripheral blood cell counts when treated with the combination of valproic acid, theophylline and all-trans retinoic acid. Leuk Res. 2009 Jun;33(6):779-87. doi: 10.1016/j.leukres.2008.10.005. Epub 2008 Nov 12.
PMID: 19007987RESULTRyningen 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. doi: 10.1517/13543784.17.11.1623.
PMID: 18922099RESULTHaaland I, Hjelle SM, Reikvam H, Sulen A, Ryningen A, McCormack E, Bruserud O, Gjertsen BT. p53 Protein Isoform Profiles in AML: Correlation with Distinct Differentiation Stages and Response to Epigenetic Differentiation Therapy. Cells. 2021 Apr 7;10(4):833. doi: 10.3390/cells10040833.
PMID: 33917201DERIVEDReikvam H, Hovland R, Forthun RB, Erdal S, Gjertsen BT, Fredly H, Bruserud O. Disease-stabilizing treatment based on all-trans retinoic acid and valproic acid in acute myeloid leukemia - identification of responders by gene expression profiling of pretreatment leukemic cells. BMC Cancer. 2017 Sep 6;17(1):630. doi: 10.1186/s12885-017-3620-y.
PMID: 28877686DERIVEDSkavland J, Jorgensen KM, Hadziavdic K, Hovland R, Jonassen I, Bruserud O, Gjertsen BT. Specific cellular signal-transduction responses to in vivo combination therapy with ATRA, valproic acid and theophylline in acute myeloid leukemia. Blood Cancer J. 2011 Feb;1(2):e4. doi: 10.1038/bcj.2011.2. Epub 2011 Feb 11.
PMID: 22829110DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Oystein Bruserud, MD
University of Bergen
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- OTHER
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Professor
Study Record Dates
First Submitted
September 9, 2005
First Posted
September 15, 2005
Study Start
November 1, 2004
Primary Completion
May 1, 2008
Study Completion
November 1, 2009
Last Updated
June 24, 2015
Record last verified: 2015-06