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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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Treatment of Acute Myelogenous Leukemia With the Histone Deacetylase Inhibitor Valproic Cid in Combination With All-trans Retinoic Acid (ATRA) and Low Dose Cytarabine

Conditions
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Acute Myelogenous Leukemia

Intervention / Treatment
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* Drug: Cytarabine, all-trans retinoic acid, valproic acid


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ATRA+valproc acid+low-dose cytarabine<br> | Drug: Cytarabine, all-trans retinoic acid, valproic acid<br>* 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<br>* Other names: No other names;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Survival |  | 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease stabilization |  | 3 years | 
| Disease complications |  | 3 years | 
| Side effects of therapy |  | 3 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Acute myelogenous leukemia, all-trans retinoic acid, valproic acid, cytarabine, Disease stabilization, survival, toxicity