Acute Myelogenous LeukemiaPhase 1/2NCT00175812
Differentiation Induction in Acute Myelogenous Leukemia
A Phase 1/2 study testing all-trans retinoic acid (ATRA), Valproic acid and Theophyllin in people with Acute Myelogenous Leukemia, run by University of Bergen at 1 site in Norway.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Acute Myelogenous Leukemia
- What is being tested?
- all-trans retinoic acid (ATRA), Valproic acid and Theophyllin
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 1 siteNorway
- Study dates
- Nov 2004to Nov 2009
- 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
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- Chronic myelogenous leukemia in blast phase
- Intolerance to the study drugs
- Serious liver disease
- No informed consent
Trial locations and contacts
1 site in 1 country.
Norway1 site
Haukeland University Hospital, University of Bergen
Bergen, N-5021
About this study
Official title: Differentiation Induction Therapy for Acute Myelogenous Leukemia
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.
Read more
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.
Read the 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.
- Conditions
- Acute Myelogenous Leukemia
- Being tested
- all-trans retinoic acid (ATRA), Valproic acid, Theophyllin
- Keywords
- Acute myelogenous leukemia, Differentiation, All trans retinoic acid, Valproic acid, Theophyllamin
- 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.
all-trans retinoic acid (ATRA)Drug
All-trans retinoic acid 22.5 mg/square meter twice daily days 1-14
Valproic acidDrug
Valproic acid, highest dose without side effects from day 3 until progression
TheophyllinDrug
Theophyllin, targetted serum level 50-100 from day 3 until progression
| Study group | Role | What they receive |
|---|---|---|
| ATRA plus valproic acid plus theophyllin | Experimental | ATRA for 14 days, continuous treatment with valproic acid and theophyllin Receives: Drug: all-trans retinoic acid (ATRA); Drug: Valproic acid; Drug: Theophyllin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Survival
Measured: 2008
Secondary outcomes (3)
Disease stabilisation
Measured: 2008
Disease complications
Measured: 2008
Side effects of therapy
Measured: 2008
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Sep 2005 (estimated)
- Study startNov 2004
- Primary completionMay 2008
- Study completionNov 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 24 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, Principal investigator, University of Bergen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00175812
- Sponsor's protocol ID
- REK-Vestnr21503
- Status last verified
- Jun 2015
- First submitted
- 9 Sep 2005
- Last updated
- 24 Jun 2015
- Results posted
- No
- Data monitoring committee
- No
Publications
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.
PubMed 19007987Ryningen 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.
PubMed 18922099Haaland 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 28877686Skavland 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.
PubMed 22829110
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
- Differentiation Induction Therapy for Acute Myelogenous Leukemia
- ClinicalTrials.gov ID
- NCT00175812
- Acronym / sponsor ID
- REK-Vestnr21503
- Conditions
- Acute Myelogenous Leukemia
- Keywords
- Acute myelogenous leukemia, Differentiation, All trans retinoic acid, Valproic acid, Theophyllamin
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 24 participants (actual)
- Lead sponsor
- University of BergenUniversity, hospital or other
- Study start
- Nov 2004
- Primary completion
- May 2008 (actual)
- Study completion
- Nov 2009 (actual)
- First posted
- 15 Sep 2005 (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: 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.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| ATRA plus valproic acid plus theophyllin | Experimental | Drug: all-trans retinoic acid (ATRA), Drug: Valproic acid, Drug: TheophyllinATRA for 14 days, continuous treatment with valproic acid and theophyllin |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (4 listed)
- Chronic myelogenous leukemia in blast phase
- Intolerance to the study drugs
- Serious liver disease
- No informed consent
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 |
|---|---|---|
| all-trans retinoic acid (ATRA)All-trans retinoic acid 22.5 mg/square meter twice daily days 1-14 | Drug | ATRA plus valproic acid plus theophyllin |
| Valproic acidValproic acid, highest dose without side effects from day 3 until progression | Drug | ATRA plus valproic acid plus theophyllin |
| TheophyllinTheophyllin, targetted serum level 50-100 from day 3 until progression | Drug | ATRA plus valproic acid plus theophyllin |
Primary outcome
Survival
Time frame: 2008
3 secondary outcomes
Disease stabilisation
Time frame: 2008
Disease complications
Time frame: 2008
Side effects of therapy
Time frame: 2008
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.
- Results publication: PubMed 19007987Ryningen 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.
- Results publication: PubMed 18922099Ryningen 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.
- 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.
- Derived from this study: PubMed 22829110Skavland 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.
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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 principal investigator
University of Bergen
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 all-trans retinoic acid (ATRA), Valproic acid and Theophyllin 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 4 inclusion and 4 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: 2008). 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 NCT00175812, which also lists 5 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.