Disease Stabilization in AML by Treatment With ATRA, Valproic Acid and Low-dose Cytarabine

Acute Myelogenous Leukemia Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00995332
• Other study ID #: Rek VEST 231-06
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: October 14, 2009
• Last updated: June 23, 2015
• Start date: September 2009
• Est. completion date: June 2013

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: 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 36
• Est. completion date: June 2013
• Est. primary completion date: February 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

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

Related Conditions & MeSH terms

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

Intervention

Drug:
• Cytarabine, all-trans retinoic acid, valproic acid
ATRA: 22.5 mg/m2 twice daily for 2 weeks every third month Valproic acid: continuous therapy, dosage guided by serum levels Cytarabine: 10 mg/m2 once daily for up to 10 days every third month

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
University of Bergen

Country where clinical trial is conducted

Norway, 

References & Publications (1)

Fredly H, Ersvær E, Kittang AO, Tsykunova G, Gjertsen BT, Bruserud O. The combination of valproic acid, all-trans retinoic acid and low-dose cytarabine as disease-stabilizing treatment in acute myeloid leukemia. Clin Epigenetics. 2013 Aug 1;5(1):13. doi: 10.1186/1868-7083-5-13. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Survival		3 years	Yes
Secondary	Disease stabilization		3 years	Yes
Secondary	Disease complications		3 years	Yes
Secondary	Side effects of therapy		3 years	Yes