Combined Therapy With Valproic Acid, All-trans Retinoic Acid (ATRA) and Cytarabine in Human Acute Myelogenous Leukemia (AML)

Condition(s) targeted: Acute Myelogenous Leukemia

Intervention: Cytarabine, all-trans retinoic acid, valproic acid (Drug)

Phase: Phase 1/Phase 2

Status: Recruiting

Sponsored by: University of Bergen

Overall contact:
Oystein Bruserud, MD, Phone: +47 55 97 29 97, Email: oystein.bruserud@haukeland.no

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.

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

Study design: Treatment, Non-Randomized, Open Label, Uncontrolled, Single Group Assignment, Safety/Efficacy Study

Primary outcome: Survival

Secondary outcome:

Disease stabilization

Disease complications

Side effects of therapy

Detailed description: Patients to be included:

1. Elderly patients (>60 years of age) or other patients unfit for conventional intensive chemotherapy with newly diagnosed acute myelogenous leukemia (AML).

2. 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.

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

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

Oystein Bruserud, MD, Phone: +47 55 97 29 97, Email: oystein.bruserud@haukeland.no

Haukeland University Hospital and University of Bergen, Bergen N-5021, Norway; Recruiting
Oystein Bruserud, MD, Phone: +47 55 97 29 97, Email: oystein.bruserud@haukeland.no
Oystein Bruserud, MD, Principal Investigator

Starting date: September 2009
Ending date: January 2015
Last updated: October 14, 2009