Differentiation Induction in Acute Myelogenous Leukemia

Acute Myelogenous Leukemia Clinical Trial

Official title:

Differentiation Induction Therapy for Acute Myelogenous Leukemia

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00175812
• Other study ID #: REK-Vestnr21503
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: September 9, 2005
• Last updated: June 23, 2015
• Start date: November 2004
• Est. completion date: November 2009

Study information

• Verified date: June 2015
• Source: University of Bergen
• Contact: n/a
• Is FDA regulated: No
• Health authority: Norway: Norwegian Medicines Agency
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 24
• Est. completion date: November 2009
• Est. primary completion date: May 2008
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Acute Myelogenous Leukemia
• Leukemia
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute

Intervention

Drug:
• all-trans retinoic acid (ATRA)
All-trans retinoic acid 22.5 mg/square meter twice daily days 1-14
• Valproic acid
Valproic acid, highest dose without side effects from day 3 until progression
• Theophyllin
Theophyllin, targetted serum level 50-100 from day 3 until progression

Locations

Country	Name	City	State
Norway	Haukeland University Hospital, University of Bergen	Bergen

Sponsors (1)

Lead Sponsor	Collaborator
University of Bergen

Country where clinical trial is conducted

Norway, 

References & Publications (2)

Ryningen A, Stapnes C, Lassalle P, Corbascio M, Gjertsen BT, Bruserud O. A subset of patients with high-risk acute myelogenous leukemia shows improved peripheral blood cell counts when treated with the combination of valproic acid, theophylline and all-tr — View Citation

Ryningen A, Stapnes C, Paulsen K, Lassalle P, Gjertsen BT, Bruserud O. In vivo biological effects of ATRA in the treatment of AML. Expert Opin Investig Drugs. 2008 Nov;17(11):1623-33. doi: 10.1517/13543784.17.11.1623 . — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Survival		2008	Yes
Secondary	Disease stabilisation		2008	Yes
Secondary	Disease complications		2008	Yes
Secondary	Side effects of therapy		2008	Yes