Overview

This trial is active, not recruiting.

Conditions chronic myelogenous leukemia, hematologic malignancies
Treatment ponatinib
Phase phase 1
Sponsor Ariad Pharmaceuticals
Start date May 2008
End date May 2016
Trial size 81 participants
Trial identifier NCT00660920, AP24534-07-101

Summary

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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Endpoint classification safety study
Intervention model single group assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
Comparison of different dosages of ponatinib given orally once per day.
ponatinib AP24534
Comparison of different dosages of drug given orally once per day.

Primary Outcomes

Measure
Maximum Tolerated Dose (MTD)
time frame: Duration of the study

Secondary Outcomes

Measure
To examine the safety of AP24534 in patients with resistant/refractory hematologic malignancies
time frame: Duration of the study
To describe the anti-tumor activity of AP24534 in patients with refractory hematologic malignancies
time frame: Duration of the study
To examine the pharmacokinetics of AP24534
time frame: Throughout the study
To examine pharmacodynamic activity of AP24534 in CML and Ph + ALL patients
time frame: Throughout the study
To describe potential pharmacogenomic markers of AP24534 anti-tumor activity
time frame: Throughout the study

Eligibility Criteria

Male or female participants at least 18 years old.

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

Additional Information

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
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.
Trial information was received from ClinicalTrials.gov and was last updated in February 2016.
Information provided to ClinicalTrials.gov by Ariad Pharmaceuticals.