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

Acute Myeloid Leukemia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT01066494
• Other study ID #: AS1413-C-101
• Status: Active, not recruiting
• Phase: Phase 2
• First received: February 9, 2010
• Last updated: January 14, 2011
• Start date: January 2010
• Est. completion date: January 2011

Study information

• Verified date: January 2011
• Source: Antisoma Research
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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)

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 20
• Est. completion date: January 2011
• Est. primary completion date: September 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Willing and able to provide written informed consent

2. In the opinion of the Investigator able to comply with the study assessments and follow-up

3. 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.

4. ECOG Performance status = 2

5. Age > 18 years and = 70 years

6. Adequate hepatic function as evidenced by the following laboratory tests:

1. Total serum bilirubin = 1.5 x ULN or direct (conjugated) bilirubin = 1.5 ULN unless attributable to suspected hepatic involvement with AML

2. Serum AST and ALT = 1.5 x ULN unless attributable to suspected hepatic involvement with AML

7. Adequate renal function as evidenced by serum creatinine = 1.5 x ULN

8. 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

9. 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

Exclusion Criteria:

1. Unwilling to accept the required per protocol blood and urine sample collection

2. An initial diagnosis of acute promyelocytic leukemia as defined by French- American-British criteria (Bennett 1976) (otherwise known as FAB M3)

3. Clinically active CNS leukemia

4. History of clinically significant allergic reactions attributed to compounds of similar chemical or biological composition to amonafide or cytarabine

5. Pregnant or breast feeding

6. Known HIV positive

7. Known active hepatitis B or C, or any other active liver disease

8. 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.

9. Any major surgery or radiation therapy within 30 days prior to study entry

10. Previously received treatment with amonafide

11. Treatment with other investigational agents for any reason within 30 days prior to study entry

12. Prior remission induction therapy for AML within 30 days of starting amonafide therapy

13. Persistent non-hematologic toxicity (other than alopecia) greater than Grade 2 from prior therapy for MDS or AML

14. Serious concomitant illnesses (for example, unstable angina or myocardial infarction or stroke within 3 months prior to study entry, congestive heart

Study Design

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

Related Conditions & MeSH terms

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

Intervention

Drug:
• Amonafide + cytarabine
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

Locations

Country	Name	City	State
Georgia	Hema - Haematology and Chemotherapy Clinic	Tbilisi
Georgia	Institute of Haematology and Transfusiology	Tbilisi
Georgia	Medulla - Chemotherapy and Immunotherapy Clinic	Tbilisi
Ukraine	Institure of URgent adn Recovery Surgery n.a. V.K. gusaka of Academy Medical Science of Ukraine	Donetsk
Ukraine	Kyiv bone Marrow Transplantation Centre	Kiev
Ukraine	Vinnytsya Regional clinical Hospital	Vinnytsya

Sponsors (1)

Lead Sponsor	Collaborator
Antisoma Research

Countries where clinical trial is conducted

Georgia,  Ukraine, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	To define the plasma PK Profile of amonafide and metabolite(s)		1 year	No
Primary	To deine the urniary excretion of amonafide and metabolite(s)		1 year	No
Primary	To investigate the fecal excretion of amonafide and metabolite(s) in selected patients		1 year	No
Primary	To evaluate the safety and tolerability of amonafide in combination with cytarabine		1 year	Yes
Primary	To evaluate the remission rate		1 year	No
Secondary	All outcomes are of equal weighting		1 year	No