Differentiation Induction in Acute Myelogenous Leukemia

University of Bergen

Status and phase: Completed; Phase 2; Phase 1

Conditions: Acute Myelogenous Leukemia

Treatments: Drug: Valproic acid; Drug: Theophyllin; Drug: all-trans retinoic acid (ATRA)

Study type: Interventional

Funder types: Other

Identifiers

NCT00175812

REK-Vestnr21503

Details and patient eligibility

About

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.

Full description

Patients to be included:

1. Elderly patients above 60 years of age with newly diagnosed acute myelogenous leukemia (AML) who cannot receive conventional intensive chemotherapy.
2. 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.

Enrollment: 24 patients

Sex: All

Ages: 18+ years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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24 participants in 1 patient group

ATRA plus valproic acid plus theophyllin

Experimental group

Description:

ATRA for 14 days, continuous treatment with valproic acid and theophyllin

Treatment:

Drug: Theophyllin

Drug: all-trans retinoic acid (ATRA)

Drug: Valproic acid