A Pharmacokinetic and Efficacy Study of Amonafide L-malate (AS1413) in Combination With Cytarabine in Patients With Acute Myeloid Leukemia (AML)

NCT01066494 | Unknown Phase 2

• 1 other identifier: AS1413-C-101
• Study Type: interventional
• Target: 20
• Locations: 2 countries
• Sites: 6

Brief Summary

A phase IIa study to evaluate the pharmacokinetic and efficacy of amonafide L-malate (AS1413) in combination with cytarabine in treating patients with acute myeloid leukemia (AML)

Conditions

Acute Myeloid Leukemia

Keywords

AML; Pgp; MDR; sAML; AS1413; Amonafide

Outcome Measures

Primary Outcomes (5)

• To define the plasma PK Profile of amonafide and metabolite(s)

  1 year

• To deine the urniary excretion of amonafide and metabolite(s)

  1 year

• To investigate the fecal excretion of amonafide and metabolite(s) in selected patients

  1 year

• To evaluate the safety and tolerability of amonafide in combination with cytarabine

  1 year

• To evaluate the remission rate

  1 year

Secondary Outcomes (1)

• All outcomes are of equal weighting

  1 year

Study Arms (1)

Single-arm

EXPERIMENTAL

Amonafide 600 mg/m2 IV over 4 hours daily on days 1-5 in combination with cytarabine 200 mg/m2 IV continuous infusion (CI) daily on days 1-7

Drug: Amonafide + cytarabine

Interventions

Amonafide + cytarabine DRUG

Amonafide 600 mg/m2 IV over 4 hours daily on days 1-5 in combination with cytarabine 200 mg/m2 IV continuous infusion (CI) daily on days 1-7

Single-arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Willing and able to provide written informed consent
• In the opinion of the Investigator able to comply with the study assessments and follow-up
• New diagnosis of AML (i.e. \>20 % blasts) as defined by the World Health Organization (WHO) classification (Vardiman 2009) or relapsed or refractory AML as defined by the persistence or recurrence of \>5% blasts in bone marrow or peripheral blood following treatment.
• ECOG Performance status ≤ 2
• Age \> 18 years and ≤ 70 years
• Adequate hepatic function as evidenced by the following laboratory tests:
• Total serum bilirubin ≤ 1.5 x ULN or direct (conjugated) bilirubin ≤ 1.5 ULN unless attributable to suspected hepatic involvement with AML
• Serum AST and ALT ≤ 1.5 x ULN unless attributable to suspected hepatic involvement with AML
• Adequate renal function as evidenced by serum creatinine ≤ 1.5 x ULN
• Women of childbearing potential must have a negative serum pregnancy test. A woman of childbearing potential is defined as one who is biologically capable of becoming pregnant. This includes women who are using contraceptives or whose sexual partners are either sterile or using contraceptives
• Left Ventricular Ejection Fraction (LVEF) \> 50%, as determined by multiplegated acquisition scan (MUGA) or echocardiogram (ECHO) within 28 days prior to administration of 1st dose of remission induction chemotherapy

You may not qualify if:

• Unwilling to accept the required per protocol blood and urine sample collection
• An initial diagnosis of acute promyelocytic leukemia as defined by French- American-British criteria (Bennett 1976) (otherwise known as FAB M3)
• Clinically active CNS leukemia
• History of clinically significant allergic reactions attributed to compounds of similar chemical or biological composition to amonafide or cytarabine
• Pregnant or breast feeding
• Known HIV positive
• Known active hepatitis B or C, or any other active liver disease
• Evidence of pulmonary infection. Patients with evidence of pulmonary infection on screening chest x-ray should have chest computed tomography (CT) prior to starting remission induction therapy to confirm absence or presence of pulmonary infection.
• Any major surgery or radiation therapy within 30 days prior to study entry
• Previously received treatment with amonafide
• Treatment with other investigational agents for any reason within 30 days prior to study entry
• Prior remission induction therapy for AML within 30 days of starting amonafide therapy
• Persistent non-hematologic toxicity (other than alopecia) greater than Grade 2 from prior therapy for MDS or AML
• Serious concomitant illnesses (for example, unstable angina or myocardial infarction or stroke within 3 months prior to study entry, congestive heart

Sponsors & Collaborators

• Antisoma Research: lead

Study Sites (6)

Institute of Haematology and Transfusiology

Tbilisi, 0177, Georgia

Location

Medulla - Chemotherapy and Immunotherapy Clinic

Tbilisi, 0186, Georgia

Location

Hema - Haematology and Chemotherapy Clinic

Tbilisi, Georgia

Location

Institure of URgent adn Recovery Surgery n.a. V.K. gusaka of Academy Medical Science of Ukraine

Donetsk, 83045, Ukraine

Location

Kyiv bone Marrow Transplantation Centre

Kiev, 03115, Ukraine

Location

Vinnytsya Regional clinical Hospital

Vinnytsia, 21018, Ukraine

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

amonafide; Cytarabine

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY

Study Record Dates

• First Submitted: February 9, 2010
• First Posted: February 10, 2010
• Study Start: January 1, 2010
• Primary Completion: September 1, 2010
• Study Completion: January 1, 2011
• Last Updated: January 17, 2011

Record last verified: 2011-01

Locations

GE (3); UA (3)