Safety Study of AP24534 to Treat Chronic Myelogenous Leukemia (CML) and Other Hematological Malignancies

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Ariad Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT00660920
First received: April 15, 2008
Last updated: February 12, 2016
Last verified: February 2016
  Purpose
The purpose of this study is to determine the maximum tolerated dose or a recommended dose of oral AP24534 in a defined schedule (QD) in patients with refractory or advanced chronic myelogenous leukemia and other refractory hematologic malignancies.

Condition Intervention Phase
Chronic Myelogenous Leukemia
Hematologic Malignancies
Drug: Ponatinib
Phase 1

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Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 1 Dose Escalation Trial to Determine the Safety, Tolerability and Maximum Tolerated Dose of Oral AP24534 in Patients With Refractory or Advanced Chronic Myelogenous Leukemia and Other Hematologic Malignancies

Resource links provided by NLM:


Further study details as provided by Ariad Pharmaceuticals:

Primary Outcome Measures:
  • Maximum Tolerated Dose (MTD) [ Time Frame: Duration of the study ] [ Designated as safety issue: Yes ]
    To determine the maximum tolerated dose or a recommended dose of oral ponatinib in a defined schedule (QD) in patients with refractory or advanced chronic myelogenous leukemia and other refractory hematologic malignancies.


Secondary Outcome Measures:
  • To examine the safety of AP24534 in patients with resistant/refractory hematologic malignancies [ Time Frame: Duration of the study ] [ Designated as safety issue: Yes ]
  • To describe the anti-tumor activity of AP24534 in patients with refractory hematologic malignancies [ Time Frame: Duration of the study ] [ Designated as safety issue: No ]
  • To examine the pharmacokinetics of AP24534 [ Time Frame: Throughout the study ] [ Designated as safety issue: No ]
  • To examine pharmacodynamic activity of AP24534 in CML and Ph + ALL patients [ Time Frame: Throughout the study ] [ Designated as safety issue: No ]
  • To describe potential pharmacogenomic markers of AP24534 anti-tumor activity [ Time Frame: Throughout the study ] [ Designated as safety issue: No ]

Enrollment: 81
Study Start Date: May 2008
Estimated Study Completion Date: May 2016
Estimated Primary Completion Date: May 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: ponatnib
Comparison of different dosages of ponatinib given orally once per day.
Drug: Ponatinib
Comparison of different dosages of drug given orally once per day.
Other Names:
  • AP24534
  • Iclusig

Detailed Description:
The purpose of this study is to determine the maximum tolerated dose or a recommended dose of oral AP24534 in a defined schedule (QD) in patients with refractory or advanced chronic myelogenous leukemia and other refractory hematologic malignancies.
  Eligibility

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

Inclusion Criteria:

  • Male or Female ≥ 18 years old
  • Diagnosed hematologic malignancy (other than lymphoma) that has relapsed or is refractory to standard care or for which no standard care is available or acceptable
  • Able to give written informed consent
  • ECOG performance status ≤ 2
  • BSA ≥ 1.5 m² (first cohort only)
  • Minimum life expectancy of 3 months or more
  • Adequate renal function defined as serum creatinine <1.5× upper limit of normal (ULN) for institution
  • Adequate hepatic function (defined as: Total bilirubin <1.5 × ULN for institution; ALT and AST <2.5 × ULN for institution [<5 X ULN if liver involvement with leukemia]; Prothrombin time <1.5 × ULN)
  • Ability to comply with study procedures in the Investigator's opinion
  • Adequate cardiac function defined as ejection fraction (EF) >40% by any method of the investigator's choice
  • Normal QTcF interval on screening ECG evaluation, defined as QTcF of <450 ms.
  • For females of childbearing potential, a negative pregnancy test must be documented prior to enrollment
  • Female patients who are of childbearing potential must agree to use an effective form of contraception with their sexual partners throughout participation in this study

Exclusion Criteria:

  • Have had cytotoxic chemotherapy or radiotherapy within 21 days prior to entering the study, or those who have not recovered from adverse events due to agents administered more than 28 days earlier with the exception of alopecia
  • Received any other investigational agents or have received an investigational agent within 14 days of starting ponatinib
  • Malabsorption syndrome or other illness which could affect oral absorption
  • Significant uncontrolled cardiac disease
  • Patients taking medicinal products that are known to be associated with prolongation of the QT interval on the electrocardiogram.
  • Uncontrolled hypertension (Diastolic BP >100 mmHg; Systolic >150 mmHg)
  • Uncontrolled intercurrent illness
  • Pregnant
  • Known infection with HIV
  • Autologous or allogeneic stem cell transplant < 3 months prior to enrollment; any evidence of ongoing graft versus host disease (GVHD), or GVHD requiring immunosuppressive therapy
  • Another primary malignancy within the past 3 years
  • Any condition or illness which, in the opinion of the investigator, would compromise patient safety or interfere with the evaluation of the safety of the drug
  • Patients taking medicinal products that are known to be associated with prolongation of the QT interval on the electrocardiogram
  • Major surgery (with the exception of intravenous catheter placement or bone marrow biopsy) within 14 days prior to initiating ponatinib therapy
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00660920

Locations
United States, California
ARIAD Investigational Site #075
San Francisco, California, United States, 94143
United States, Michigan
ARIAD Investigational Site #011
Ann Arbor, Michigan, United States, 48109
United States, Oregon
ARIAD Investigational Site #048
Portland, Oregon, United States, 97239
United States, Tennessee
ARIAD Investigational Site #076
Nashville, Tennessee, United States, 37203
United States, Texas
ARIAD Investigational Site #005
Houston, Texas, United States, 70030
Sponsors and Collaborators
Ariad Pharmaceuticals
  More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Ariad Pharmaceuticals
ClinicalTrials.gov Identifier: NCT00660920     History of Changes
Other Study ID Numbers: AP24534-07-101 
Study First Received: April 15, 2008
Last Updated: February 12, 2016
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Leukemia
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Leukemia, Myeloid
Neoplasms
Bone Marrow Diseases
Hematologic Diseases
Myeloproliferative Disorders
Neoplasms by Histologic Type
Ponatinib
Antineoplastic Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Protein Kinase Inhibitors
Therapeutic Uses

ClinicalTrials.gov processed this record on April 27, 2016