Clinical trial NCT01592136: Expanded Access Program of Ponatinib
Official title: Expanded Access Program of Ponatinib (AP24534) for Patients With Refractory Chronic Myeloid Leukemia or Ph+ Acute Lymphoblastic Leukemia
Study type: EXPANDED_ACCESS
Overall status: APPROVED_FOR_MARKETING
Conditions: Chronic Myeloid Leukemia (CML)
Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia (Ph+ ALL)
Keywords: Ponatinib
Tyrosine kinase inhibitor
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2012-05-07
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT

Brief summary: This protocol will allow expanded access of ponatinib to patients ≥18 years with chronic myeloid leukemia (CML) any phase or Philadelphia chromosome positive acute lymphoblastic leukemia (Ph+ALL) who have failed all available treatment options.

Detailed description: 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.

Eligibility criteria: 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 exclusion criteria:

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.

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: La Jolla
country: United States
facility: Moores UCSD Cancer Center, Site #165
state: California
city: San Marcos
country: United States
facility: Southern California Permanente Medical Group, Site #161
state: California
city: Vallejo
country: United States
facility: Kaiser Permanente Medical Center, Site #158
state: California
city: New Haven
country: United States
facility: Smilow Cancer Hospital at Yale New Haven, Site #182
state: Connecticut
city: Altamonte Springs
country: United States
facility: Cancer Institute of Florida, Site #187
state: Florida
city: Tampa
country: United States
facility: H. Lee Moffitt Cancer Center & Research Institute, Site #017
state: Florida
city: Atlanta
country: United States
facility: Emory University, Site # 058
state: Georgia
city: Chicago
country: United States
facility: University of Chicago Medical Center, Site #001
state: Illinois
city: Indianapolis
country: United States
facility: Indiana Blood and Marrow Transplantation, Site #138
state: Indiana
city: Louisville
country: United States
facility: Norton Cancer Institute, Site #142
state: Kentucky
city: Baltimore
country: United States
facility: University of Maryland, Site #040
state: Maryland
city: Boston
country: United States
facility: Tufts Medical Center, Site #141
state: Massachusetts
city: Boston
country: United States
facility: Dana-Farber Cancer Institute, Site 008
state: Massachusetts
city: Worcester
country: United States
facility: University of Massachusetts Worcester, Site #152
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan Health System, Site #011
state: Michigan
city: Detroit
country: United States
facility: Karmanos Cancer Institute, Site #034
state: Michigan
city: Rochester
country: United States
facility: Mayo Clinic, Site #044
state: Minnesota
city: Joplin
country: United States
facility: Freeman Cancer Institute, Site #190
state: Missouri
city: Saint Louis
country: United States
facility: Washington University School of Medicine, Site 007
state: Missouri
city: Hackensack
country: United States
facility: John Theurer Cancer Center at Hackensack University Medical Center, Site 128
state: New Jersey
city: Buffalo
country: United States
facility: Roswell Park Cancer Institute, Site #029
state: New York
city: New York
country: United States
facility: Weill Cornell Medical College - New York Presbyterian Hospital, Site #006
state: New York
city: Rochester
country: United States
facility: University of Rochester, Site 137
state: New York
city: Durham
country: United States
facility: Duke University Medical Center, Site 003
state: North Carolina
city: Cincinnati
country: United States
facility: Jewish Hospital, Site #175
state: Ohio
city: Portland
country: United States
facility: Oregon Health & Science University (OHSU), Site 048
state: Oregon
city: Philadelphia
country: United States
facility: Hospital of the University of Pennsylvania, Site #013
state: Pennsylvania
city: Philadelphia
country: United States
facility: Jeanes Hospital of TUHS, Site #127
state: Pennsylvania
city: Charleston
country: United States
facility: Medical University of South Carolina, Site #148
state: South Carolina
city: Nashville
country: United States
facility: Tennesse Oncology, PLLC, Site # 076
state: Tennessee
city: Houston
country: United States
facility: The University of Texas M.D. Anderson Cancer Center, Site #005
state: Texas
city: Salt Lake City
country: United States
facility: Huntsman Cancer Institute at the University of Utah, Site #043
state: Utah
city: Seattle
country: United States
facility: Seattle Cancer Care Alliance, Site #100
state: Washington
Study officials:
References: