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

Recruitment & Eligibility

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

Study & Design

Arm && Interventions

Group	Intervention	Description
ponatnib	Ponatinib	Comparison of different dosages of ponatinib given orally once per day.

Primary Outcome Measures

Name	Time	Method
Determine Maximum Tolerated Dose (MTD) or Recommended dose	Up to	Determine MTD 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

Name	Time	Method
To describe potential pharmacogenomic markers of AP24534 anti-tumor activity	Up to 7 years
To examine the safety of AP24534 in patients with resistant/refractory hematologic malignancies	Up to 7 years
To describe the anti-tumor activity of AP24534 in patients with refractory hematologic malignancies	Up to 7 years
To examine pharmacodynamic activity of AP24534 in CML and Ph + ALL patients	Up to 7 years
To examine the pharmacokinetics of AP24534	Up to 2 cycles (1 cycle = 28 days)

Trial Locations

Locations (5)

ARIAD Investigational Site #076

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Nashville, Tennessee, United States

ARIAD Investigational Site #005

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Houston, Texas, United States

ARIAD Investigational Site #075

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San Francisco, California, United States

ARIAD Investigational Site #011

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Ann Arbor, Michigan, United States

ARIAD Investigational Site #048

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Portland, Oregon, United States

Recruitment & Eligibility