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Study of the Safety, Tolerability, Pharmacokinetics and Pharmacodynamic Properties of Oral AT-406 in Combination With Daunorubicin and Cytarabine in Patients With Poor-risk Acute Myelogenous Leukemia (AML)

This study has been terminated.
(Study was terminated before a MTD was determined for administrative reasons)
Sponsor:
Collaborator:
The Leukemia and Lymphoma Society
Information provided by (Responsible Party):
Ascenta Therapeutics
ClinicalTrials.gov Identifier:
NCT01265199
First received: December 20, 2010
Last updated: January 21, 2013
Last verified: January 2013
History of Changes
  Purpose

The main purpose of this study are to determine the maximum dose of AT-406 that can be safely given in combination with cytarabine and daunorubicin to humans. Other purposes are to determine how the drug is broken down in the body, and to see if there are any molecular interactions that can help determine how AT-406 works. Side effects will also be studied in an effort to make sure that this drug is safe to take.


Condition Intervention Phase
Acute Myelogenous Leukemia (AML)
 Drug: AT-406 in combination with daunorubicin and cytarabine
 Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I Dose Escalation Study of the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamic Properties of Oral AT-406 in Combination With Daunorubicin and Cytarabine in Patients With Poor-risk, Acute Myelogenous Leukemia (AML)

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by Ascenta Therapeutics:

Primary Outcome Measures:
  • Determine Number of Participants with Adverse Events as a Measure of Safety and Tolerability of oral AT-406 in combination with daunorubicin and cytarabine. [ Time Frame: 15 months ] [ Designated as safety issue: Yes ]
    Determine Number of Participants with Adverse Events as a Measure of Safety and Tolerability of AT-101.


Secondary Outcome Measures:
  • Determine the pharmacokinetic profile of AT-406 and daunorubicin and cytarabine [ Time Frame: 15 months ] [ Designated as safety issue: No ]
    To determine how the drug is absorbed, distributed, metabolized, and eliminated by the body.


Enrollment: 29
Study Start Date: February 2011
Study Completion Date: January 2013
Primary Completion Date: January 2013 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: AT-406 in combination with daunorubicin and cytarabine
    Oral AT-406 (capsule) given once daily on days 1-5 of induction therapy with daunorubicin 90 mg/m2 I.v. on days 1-3 and cytarabine 100 mg/m2 i.v. by continuous infusion on days 107 of induction therapy.
Detailed Description:

This is an open label, multi-center, dose escalation study to determine the MTD of oral AT-406 combined with daunorubicin and cytarabine in patients with poor-risk AML. Treatment with AT-406 will be administered to up to 60 patients at approximately 7 investigational sites in the US. Patients will be enrolled in open label sequential cohorts of up to 12 patients to determine the MTD of AT-406 in combination with daunorubicin and cytarabine. Dose finding will occur during the induction cycle of the regimen. AT-406 will not be administered in consolidation cycles. Patients who require re-induction during initial treatment will be removed from the study and replaced (if needed) in order to assess at least 3 evaluable patients at each dose level.

Clinical and laboratory parameters will be assessed to evaluate the toxicity of AT-406. In addition, pharmacokinetic (PK) and pharmacodynamic (PDy) blood samples will be analyzed for plasma concentrations and PDy effect of AT-406, respectively.

  Eligibility

Ages Eligible for Study:   18 Years to 74 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Eligibility Criteria:

Inclusion:

  • Male or females patients ages 18 to 74
  • Morphological diagnosis of untreated or relapsed non-M3 AML according to WHO diagnostic criteria who exhibit at least one poor-risk feature and are not be known to exhibit any favorable cytogenetic features or variants.
  • Patients with relapsed AML and patients with prior autologous or allogeneic hematopoietic stem cell transplantations are eligible if relapse occurred following a remission of ≥ 6 months.
  • Patients must have an ECOG score of ≤ 2,
  • Adequate cardiac, liver and renal function.

Exclusion:

  • Must not have any evidence of CNS leukemia.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01265199

Locations
United States, Illinois
Univerity of Chicago
Chicago, Illinois, United States
United States, Michigan
University of Michigan Health System
Ann Arbor, Michigan, United States
United States, Missouri
Washington University at St. Louis Siteman Cancer Center
St. Louis, Missouri, United States
United States, New York
Memorial Sloan Kettering Cancer Center
New York, New York, United States
United States, Pennsylvania
Hospital of the University of Pennsylvania
Philadelphia, Pennsylvania, United States
Temple University at Jeanes Hospital
Philadelphia, Pennsylvania, United States
Sponsors and Collaborators
Ascenta Therapeutics
The Leukemia and Lymphoma Society
Investigators
Study Director: J. Mel Sorensen, MD Ascenta Therapeutics, Inc.
  More Information

No publications provided

Responsible Party: Ascenta Therapeutics
ClinicalTrials.gov Identifier: NCT01265199     History of Changes
Other Study ID Numbers: AT-406-CS-002
Study First Received: December 20, 2010
Last Updated: January 21, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Ascenta Therapeutics:
AML

Additional relevant MeSH terms:
Leukemia
Leukemia, Myeloid, Acute
Leukemia, Myeloid
Neoplasms by Histologic Type
Neoplasms
Cytarabine
Daunorubicin
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
Antibiotics, Antineoplastic

ClinicalTrials.gov processed this record on May 16, 2013