Differentiation Induction in Acute Myelogenous Leukemia

Study Overview
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Brief Summary
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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
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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.

Official Title
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Differentiation Induction Therapy for Acute Myelogenous Leukemia

Conditions
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Acute Myelogenous Leukemia

Intervention / Treatment
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* Drug: all-trans retinoic acid (ATRA)
* Drug: Valproic acid
* Drug: Theophyllin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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 Exclusion Criteria: Chronic myelogenous leukemia in blast phase Intolerance to the study drugs Serious liver disease No informed consent

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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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ATRA plus valproic acid plus theophyllin<br>ATRA for 14 days, continuous treatment with valproic acid and theophyllin | Drug: all-trans retinoic acid (ATRA)<br>* All-trans retinoic acid 22.5 mg/square meter twice daily days 1-14<br>Drug: Valproic acid<br>* Valproic acid, highest dose without side effects from day 3 until progression<br>Drug: Theophyllin<br>* Theophyllin, targetted serum level 50-100 from day 3 until progression<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Survival |  | 2008 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease stabilisation |  | 2008 | 
| Disease complications |  | 2008 | 
| Side effects of therapy |  | 2008 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Acute myelogenous leukemia, Differentiation, All trans retinoic acid, Valproic acid, Theophyllamin