Acute Myelogenous LeukemiaPhase 1/2NCT00995332
Disease Stabilization in AML by Treatment With ATRA, Valproic Acid and Low-dose Cytarabine
A Phase 1/2 study testing Cytarabine, all-trans retinoic acid, valproic acid in people with Acute Myelogenous Leukemia, run by University of Bergen at 1 site in Norway.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Acute Myelogenous Leukemia
- What is being tested?
- Cytarabine, all-trans retinoic acid, valproic acid
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 36 participants
- Where
- 1 siteNorway
- Study dates
- Sep 2009to Jun 2013
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Recently diagnosed AML in patients unfit for intensive chemotherapy
- Patients with relapsed or refractory AML
Who cannot join
- No informed consent
- Intolerance to study drugs
- Serious liver disease
Trial locations and contacts
1 site in 1 country.
Norway1 site
Haukeland University Hospital and University of Bergen
Bergen, N-5021
About this study
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
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.
Read the detailed description
Patients to be included:
- Elderly patients (>60 years of age) or other patients unfit for conventional intensive chemotherapy with newly diagnosed acute myelogenous leukemia (AML).
- 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.
- Conditions
- Acute Myelogenous Leukemia
- Being tested
- Cytarabine, all-trans retinoic acid, valproic acid
- Keywords
- Acute myelogenous leukemia, all-trans retinoic acid, valproic acid, cytarabine, Disease stabilization, survival, toxicity
- Medical subject headings
- Leukemia, Myeloid, Acute
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Cytarabine, all-trans retinoic acid, valproic acidDrug
Also called No other names
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
| Study group | Role | What they receive |
|---|---|---|
| ATRA+valproc acid+low-dose cytarabine | Experimental | Not described Receives: Drug: Cytarabine, all-trans retinoic acid, valproic acid |
What is being measured
The primary outcome is the main question the study is designed to answer.
Survival
Measured: 3 years
Secondary outcomes (3)
Disease stabilization
Measured: 3 years
Disease complications
Measured: 3 years
Side effects of therapy
Measured: 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Oct 2009 (estimated)
- Study startSep 2009
- Primary completionFeb 2013
- Study completionJun 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Acute Myelogenous LeukemiaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 36 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Bergen
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Øystein Bruserud, University of Bergen
- Investigators
- Oystein Bruserud, MD, Study chair, University of Bergen, Norway
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00995332
- Sponsor's protocol ID
- Rek VEST 231-06
- Status last verified
- Jun 2015
- First submitted
- 14 Oct 2009
- Last updated
- 24 Jun 2015
- Results posted
- No
- Data monitoring committee
- No
Publications
Fredly H, Ersvaer E, Kittang AO, Tsykunova G, Gjertsen BT, Bruserud O. The combination of valproic acid, all-trans retinoic acid and low-dose cytarabine as disease-stabilizing treatment in acute myeloid leukemia. Clin Epigenetics. 2013 Aug 1;5(1):13. doi: 10.1186/1868-7083-5-13.
PubMed 23915396Haaland 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.
PubMed 33917201Reikvam 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.
PubMed 28877686
Study at a glance
From the registry record, last updated by the sponsor on 24 Jun 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT00995332
- Acronym / sponsor ID
- Rek VEST 231-06
- Conditions
- Acute Myelogenous Leukemia
- Keywords
- Acute myelogenous leukemia, all-trans retinoic acid, valproic acid, cytarabine, Disease stabilization, survival, toxicity
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 36 participants (actual)
- Lead sponsor
- University of BergenUniversity, hospital or other
- Study start
- Sep 2009
- Primary completion
- Feb 2013 (actual)
- Study completion
- Jun 2013 (actual)
- First posted
- 15 Oct 2009 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Patients to be included:
- Elderly patients (>60 years of age) or other patients unfit for conventional intensive chemotherapy with newly diagnosed acute myelogenous leukemia (AML).
- 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| ATRA+valproc acid+low-dose cytarabine | Experimental | Drug: Cytarabine, all-trans retinoic acid, valproic acid |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Recently diagnosed AML in patients unfit for intensive chemotherapy
- Patients with relapsed or refractory AML
Key exclusion criteria (3 listed)
- No informed consent
- Intolerance to study drugs
- Serious liver disease
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Cytarabine, all-trans retinoic acid, valproic acidAlso: No other namesATRA: 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 | Drug | ATRA+valproc acid+low-dose cytarabine |
Primary outcome
Survival
Time frame: 3 years
3 secondary outcomes
Disease stabilization
Time frame: 3 years
Disease complications
Time frame: 3 years
Side effects of therapy
Time frame: 3 years
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Jun 2015.
- Background: PubMed 23915396Fredly H, Ersvaer E, Kittang AO, Tsykunova G, Gjertsen BT, Bruserud O. The combination of valproic acid, all-trans retinoic acid and low-dose cytarabine as disease-stabilizing treatment in acute myeloid leukemia. Clin Epigenetics. 2013 Aug 1;5(1):13. doi: 10.1186/1868-7083-5-13.
- Derived from this study: PubMed 33917201Haaland 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.
- Derived from this study: PubMed 28877686Reikvam 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Oystein Bruserud, MD study chair
University of Bergen, Norway
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Cytarabine, all-trans retinoic acid, valproic acid in people with Acute Myelogenous Leukemia, run by University of Bergen at 1 site in Norway.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 24 Jun 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Norway. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Survival (time frame: 3 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00995332, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Jun 2015.