This protocol will allow expanded access of ponatinib to patients ≥18 years with CML or Ph+ALL who have failed all available treatment options. Patients with chronic (CP) or accelerated phase (AP) CML must be previously treated with and resistant or intolerant to imatinib, dasatinib and nilotinib or develop the T315I mutation after any tyrosine kinase inhibitor (TKI) therapy. Patients with blast phase (BP) CML and Ph+ ALL must be previously treated with and resistant or intolerant to imatinib and dasatinib or develop the T315I mutation after any TKI therapy. No formal analysis will be performed on any data obtained. Safety information will be collected and adverse events will be tabulated for reporting purposes only.
Patients will receive ponatinib 45 mg orally as a single dose once daily with or without food. Each patient will receive daily ponatinib until disease progression, unacceptable toxicity, or withdrawal of consent
Other Name: AP24534
Main Inclusion Criteria:
1. CP-CML and AP-CML patients previously treated with and resistant or intolerant to imatinib, dasatinib and nilotinib or those who developed the T315I mutation after any TKI therapy. BP-CML and Ph+ ALL patients previously treated with and resistant or intolerant to imatinib and dasatinib or those who developed the T315I mutation after any TKI therapy.
2. Patients must be ≥ 18 years old.
3. Provide written informed consent.
4. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.
5. Men and women of childbearing potential must agree to effective contraception from the time of signing informed consent through the Follow-up Visit, approximately 30 days after last dose of ponatinib.
Main Exclusion Criteria:
Patients are not eligible for participation in the study if they meet any of the following
1. Are eligible for an ongoing and accessible clinical trial of ponatinib
2. Have not adequately recovered from AEs due to agents previously administered
3. Require concurrent treatment with immunosuppressive agents, other than corticosteroids prescribed for a short course of therapy.
4. Have previously been treated with ponatinib.
5. Have significant or active cardiovascular disease, specifically including, but not restricted to: - Myocardial infarction within 3 months prior to first dose of ponatinib, - History of clinically significant atrial arrhythmia or any ventricular arrhythmia, - Unstable angina within 3 months prior to first dose of ponatinib, - Congestive heart failure within 3 months prior to first dose of ponatinib.
6. Have abnormal QTcF (> 450 ms for males or > 470 ms for females)
7. Have a significant bleeding disorder unrelated to CML or Ph+ ALL.
8. Have a history of pancreatitis or alcohol abuse
9. Have elevated amylase or lipase (> 1.5 x ULN for institution) at entry.
10. Have inadequate hepatic function or any of the following: - Total bilirubin > 1.5 x ULN for institution at entry - Alanine aminotransferase and aspartate aminotransferase > 2.5 x ULN for institution at entry - Prothrombin time >1.5 x ULN for institution at entry
11. Have inadequate renal function or serum creatinine > 2.5 x ULN for institution at entry
12. Have uncontrolled hypertriglyceridemia or triglycerides > 450 mg/dL at entry.
13. Have malabsorption syndrome or other gastrointestinal illness that could affect absorption of orally administered ponatinib.
14. Women who are pregnant or lactating.
15. Underwent major surgery within 14 days prior to the first dose of ponatinib.
16. Have ongoing or active infection (including known history of human immunodeficiency virus [HIV], hepatitis B virus [HBV], or hepatitis C virus [HCV]).
17. Suffer from any condition or illness that, in the opinion of the Investigator would compromise patient safety or interfere with the evaluation of the safety of the study drug.
Moores UCSD Cancer Center, Site #165
La Jolla, California, 92093
Southern California Permanente Medical Group, Site #161
San Marcos, California, 92069
Kaiser Permanente Medical Center, Site #158
Vallejo, California, 94589
Smilow Cancer Hospital at Yale New Haven, Site #182
New Haven, Connecticut, 06510
Cancer Institute of Florida, Site #187
Altamonte Springs, Florida, 32792
H. Lee Moffitt Cancer Center & Research Institute, Site #017
Tampa, Florida, 33612
Emory University, Site # 058
Atlanta, Georgia, 30322
University of Chicago Medical Center, Site #001
Chicago, Illinois, 60637
Indiana Blood and Marrow Transplantation, Site #138
Indianapolis, Indiana, 46237
Norton Cancer Institute, Site #142
Louisville, Kentucky, 40202
University of Maryland, Site #040
Baltimore, Maryland, 21201
Tufts Medical Center, Site #141
Boston, Massachusetts, 02111
Dana-Farber Cancer Institute, Site 008
Boston, Massachusetts, 02215
University of Massachusetts Worcester, Site #152
Worcester, Massachusetts, 01655
University of Michigan Health System, Site #011
Ann Arbor, Michigan, 48109
Karmanos Cancer Institute, Site #034
Detroit, Michigan, 48201
Mayo Clinic, Site #044
Rochester, Minnesota, 55905
Freeman Cancer Institute, Site #190
Joplin, Missouri, 64804
Washington University School of Medicine, Site 007
Saint Louis, Missouri, 63110
John Theurer Cancer Center at Hackensack University Medical Center, Site 128
Hackensack, New Jersey, 07601
Roswell Park Cancer Institute, Site #029
Buffalo, New York, 14263
Weill Cornell Medical College - New York Presbyterian Hospital, Site #006
New York, New York, 10065
University of Rochester, Site 137
Rochester, New York, 14627
Duke University Medical Center, Site 003
Durham, North Carolina, 27710
Jewish Hospital, Site #175
Cincinnati, Ohio, 45236
Oregon Health & Science University (OHSU), Site 048
Portland, Oregon, 97239
Hospital of the University of Pennsylvania, Site #013
Philadelphia, Pennsylvania, 19104
Jeanes Hospital of TUHS, Site #127
Philadelphia, Pennsylvania, 19111
Medical University of South Carolina, Site #148
Charleston, South Carolina, 29425
Tennesse Oncology, PLLC, Site # 076
Nashville, Tennessee, 37203
The University of Texas M.D. Anderson Cancer Center, Site #005
Houston, Texas, 77030
Huntsman Cancer Institute at the University of Utah, Site #043
Salt Lake City, Utah, 84112
Seattle Cancer Care Alliance, Site #100
Seattle, Washington, 98109
Expanded Access program information for companies listed in the Expanded Access Company Directory is pulled daily from ClinicalTrials.gov, a resource provided by the National Institutes of Health in cooperation with the U.S. Food and Drug Administration. Click here for more information about ClinicalTrials.gov.