Differentiation Induction in Acute Myelogenous Leukemia

Condition(s) targeted: Acute Myelogenous Leukemia

Intervention: all-trans retinoic acid (ATRA)+valproic acid+theophyllamin (Drug)

Phase: Phase 1/Phase 2

Status: Recruiting

Sponsored by: University of Bergen

Official(s) and/or principal investigator(s):
Oystein Bruserud, MD, Principal Investigator, Affiliation: University of Bergen

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.

Official title: Differentiation Induction Therapy for Acute Myelogenous Leukemia

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

Primary outcome: Survival

Secondary outcome:

Disease stabilisation

Disease complications

Side effects of therapy

Detailed 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.

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

Criteria:

Inclusion Criteria:

- recently diagnosed acute myelogenous leukemia (AML)in patients above 60 years of age

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.

Haukeland University Hospital, University of Bergen, Bergen N-5021, Norway; Recruiting
Oystein Bruserud, MD, Phone: +47 55 97 50 00, Email: oystein.bruserud@haukeland.no
Peter Ernst, MD, Phone: +47 55 97 50 00, Email: peter.ernst@med.uib.no
Oystein Bruserud, MD, Principal Investigator

Related publications:

Raffoux E, Chaibi P, Dombret H, Degos L. Valproic acid and all-trans retinoic acid for the treatment of elderly patients with acute myeloid leukemia. Haematologica. 2005 Jul;90(7):986-8.

Trus MR, Yang L, Suarez Saiz F, Bordeleau L, Jurisica I, Minden MD. The histone deacetylase inhibitor valproic acid alters sensitivity towards all trans retinoic acid in acute myeloblastic leukemia cells. Leukemia. 2005 Jul;19(7):1161-8.

Pilatrino C, Cilloni D, Messa E, Morotti A, Giugliano E, Pautasso M, Familiari U, Cappia S, Pelicci PG, Lo Coco F, Saglio G, Guerrasio A. Increase in platelet count in older, poor-risk patients with acute myeloid leukemia or myelodysplastic syndrome treated with valproic acid and all-trans retinoic acid. Cancer. 2005 Jul 1;104(1):101-9.

Kuendgen A, Strupp C, Aivado M, Bernhardt A, Hildebrandt B, Haas R, Germing U, Gattermann N. Treatment of myelodysplastic syndromes with valproic acid alone or in combination with all-trans retinoic acid. Blood. 2004 Sep 1;104(5):1266-9. Epub 2004 May 20.

Starting date: November 2004
Ending date: November 2009
Last updated: April 19, 2007