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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.
Patients to be included:
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| ATRA+valproc acid+low-dose cytarabine | Experimental |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Cytarabine, all-trans retinoic acid, valproic acid | Drug | 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 |
| Measure | Description | Time Frame |
|---|---|---|
| Survival | 3 years |
| Measure | Description | Time Frame |
|---|---|---|
| Disease stabilization | 3 years | |
| Disease complications | 3 years | |
| Side effects of therapy |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Oystein Bruserud, MD | University of Bergen, Norway | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Haukeland University Hospital and University of Bergen | Bergen | N-5021 | Norway |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 23915396 | Background | 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. | |
| 33917201 | Derived | Haaland 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. |
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| ID | Term |
|---|---|
| D015470 | Leukemia, Myeloid, Acute |
| ID | Term |
|---|---|
| D007951 | Leukemia, Myeloid |
| D007938 | Leukemia |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
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Not provided
| ID | Term |
|---|---|
| D003561 | Cytarabine |
| D014212 | Tretinoin |
| D014635 | Valproic Acid |
| ID | Term |
|---|---|
| D003562 | Cytidine |
| D011741 | Pyrimidine Nucleosides |
| D011743 | Pyrimidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
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|
| 3 years |
| 28877686 | Derived | Reikvam 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. |
| D006402 |
| Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D006571 |
| Heterocyclic Compounds |
| D001087 | Arabinonucleosides |
| D009705 | Nucleosides |
| D009706 | Nucleic Acids, Nucleotides, and Nucleosides |
| D014801 | Vitamin A |
| D012176 | Retinoids |
| D002338 | Carotenoids |
| D011090 | Polyenes |
| D000475 | Alkenes |
| D006839 | Hydrocarbons, Acyclic |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D053138 | Cyclohexenes |
| D003510 | Cyclohexanes |
| D003516 | Cycloparaffins |
| D006840 | Hydrocarbons, Alicyclic |
| D006844 | Hydrocarbons, Cyclic |
| D013729 | Terpenes |
| D004224 | Diterpenes |
| D010860 | Pigments, Biological |
| D001685 | Biological Factors |
| D010421 | Pentanoic Acids |
| D014631 | Valerates |
| D000144 | Acids, Acyclic |
| D002264 | Carboxylic Acids |
| D005232 | Fatty Acids, Volatile |
| D005227 | Fatty Acids |
| D008055 | Lipids |