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

The recruitment status of this study is unknown because the information has not been verified recently.
Verified January 2011 by Antisoma Research.
Recruitment status was  Active, not recruiting
Sponsor:
Information provided by:
Antisoma Research
ClinicalTrials.gov Identifier:
NCT01066494
First received: February 9, 2010
Last updated: January 14, 2011
Last verified: January 2011
  Purpose

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)


Condition Intervention Phase
Acute Myeloid Leukemia
Drug: Amonafide + cytarabine
Phase 2

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

Resource links provided by NLM:


Further study details as provided by Antisoma Research:

Primary Outcome Measures:
  • To define the plasma PK Profile of amonafide and metabolite(s) [ Time Frame: 1 year ] [ Designated as safety issue: No ]
  • To deine the urniary excretion of amonafide and metabolite(s) [ Time Frame: 1 year ] [ Designated as safety issue: No ]
  • To investigate the fecal excretion of amonafide and metabolite(s) in selected patients [ Time Frame: 1 year ] [ Designated as safety issue: No ]
  • To evaluate the safety and tolerability of amonafide in combination with cytarabine [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
  • To evaluate the remission rate [ Time Frame: 1 year ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • All outcomes are of equal weighting [ Time Frame: 1 year ] [ Designated as safety issue: No ]

Estimated Enrollment: 20
Study Start Date: January 2010
Estimated Study Completion Date: January 2011
Estimated Primary Completion Date: September 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Single-arm
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
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

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01066494

Locations
Georgia
Medulla - Chemotherapy and Immunotherapy Clinic
Tbilisi, Georgia, 0186
Hema - Haematology and Chemotherapy Clinic
Tbilisi, Georgia
Institute of Haematology and Transfusiology
Tbilisi, Georgia, 0177
Ukraine
Institure of URgent adn Recovery Surgery n.a. V.K. gusaka of Academy Medical Science of Ukraine
Donetsk, Ukraine, 83045
Kyiv bone Marrow Transplantation Centre
Kiev, Ukraine, 03115
Vinnytsya Regional clinical Hospital
Vinnytsya, Ukraine, 21018
Sponsors and Collaborators
Antisoma Research
  More Information

No publications provided

Responsible Party: Fredrik Erlandsson, Antisoma
ClinicalTrials.gov Identifier: NCT01066494     History of Changes
Other Study ID Numbers: AS1413-C-101
Study First Received: February 9, 2010
Last Updated: January 14, 2011
Health Authority: United States: Food and Drug Administration

Keywords provided by Antisoma Research:
AML
Pgp
MDR
sAML
AS1413
Amonafide

Additional relevant MeSH terms:
Leukemia
Leukemia, Myeloid, Acute
Leukemia, Myeloid
Neoplasms by Histologic Type
Neoplasms
Cytarabine
Amonafide
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Antiviral Agents
Anti-Infective Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Enzyme Inhibitors

ClinicalTrials.gov processed this record on April 16, 2014