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

ARIAD Pharmaceuticals

Status and phase

Completed

Phase 1

Conditions

Chronic Myelogenous Leukemia

Hematologic Malignancies

Treatments

Drug: Ponatinib

Study type

Interventional

Funder types

Industry

Identifiers

NCT00660920

AP24534-07-101

Details and patient eligibility

About

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

Enrollment

81 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

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