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A Pivotal Phase 2 Trial of Ponatinib (AP24534) in Patients With Refractory Chronic Myeloid Leukemia and Ph+ Acute Lymphoblastic Leukemia


Phase 2
18 Years
N/A
Open (Enrolling)
Both
Chronic Myeloid Leukemia (CML), Ph+ Acute Lymphoblastic Leukemia (ALL)

Thank you

Trial Information

A Pivotal Phase 2 Trial of Ponatinib (AP24534) in Patients With Refractory Chronic Myeloid Leukemia and Ph+ Acute Lymphoblastic Leukemia


The preliminary analysis of the phase 1 clinical trial revealed evidence of clinical
antitumor activity in patients with resistance to approved second-generation tyrosine kinase
inhibitors (TKI), dasatinib and nilotinib, including patients with the T315I mutation of
BCR-ABL. This study, taken together with the strong preclinical data that characterize
ponatinib, provides the rationale for moving to a pivotal phase 2 trial of this agent in a
population of patients with chronic myeloid leukemia (CML) and Ph+ Acute Lymphoblastic
Leukemia (ALL) who are resistant or intolerant to prior TKI therapy and in those patients
with the T315I mutation.


Inclusion Criteria:



- Previously treated with and developed resistance or intolerance to dasatinib or
nilotinib, or developed the T3151 mutation after any TKI therapy including imatinib

- ≥18 years old

- ECOG performance status ≤2

- Normal pancreatic function

- QTcF interval ≤450 ms for males and ≤470 ms for females

- Adequate renal and hepatic function

- Minimum life expectancy of ≥3 months

- Provide written informed consent

- Negative pregnancy test and agree to use effective form of contraception (if
applicable)

Exclusion Criteria:

- Received prior tyrosine kinase inhibitor (TKI) treatment within 7 days prior to
receiving the first dose of ponatinib

- Received other therapies as follows:

1. For CML chronic phase (CP) and accelerated phase (AP) patients, received
hydroxyurea or anagrelide within 24 hours prior to receiving the first dose of
ponatinib; interferon, cytarabine, or immunotherapy within 14 days prior to
first dose of ponitinib; or any other cytotoxic chemotherapy, radiotherapy, or
investigational therapy within 28 days prior to receiving the first dose of
ponatinib.

2. For CML blast phase (BP) patients, received chemotherapy within 14 days prior to
the first dose of ponatinib.

3. For Ph+ ALL patients, received corticosteroids within 24 hours before the first
dose of ponatinib; or vincristine within 7 days prior to the first dose of
ponatinib; or received other chemotherapy within 14 days prior to the first dose
of ponatinib.

4. All patients are excluded if they have not recovered from adverse events except
alopecia) resulting from any prior treatments administered.

- Taking medications that are known to be associated with torsades de pointes

- Previously treated with ponatinib

- Underwent stem cell transplant <60 days prior to receiving first dose of ponatinib

- Evidence of on-going graft versus-host disease (GVHD), or GVHD requiring
immunosuppressive therapy

- Require concurrent treatment with immunosuppressive agents

- Have active Central Nervous System (CNS) disease

- Have significant or active cardiovascular disease

- Have a significant bleeding disorder unrelated to CML or Ph+ALL

- Have a history of pancreatitis or alcohol abuse

- Have uncontrolled hypertriglyceridemia (triglycerides >450 mg/dL)

- Underwent major surgery within 14 days prior to first dose of ponatinib

- Have ongoing or active infection

- Have malabsorption syndrome or other gastrointestinal illness that could affect
absorption of ponatinib

- Diagnosed with another primary malignancy in the past 3 years

- Pregnant or lactating

- Suffer from any other condition or illness that would compromise safety

Type of Study:

Interventional

Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Major cytogenetic response (MCyR) CP patients, and Major Hematologic Response (MaHR) AP/BP and Ph+ ALL patients

Outcome Description:

For CML patients in CP at study entry: major cytogenetic response (MCyR), defined as complete cytogenetic response (CCyR) or partial cytogenetic response (PCyR). CP patients in CCyR are not eligible for this study. For CML patients in AP at study entry: major hematologic response (MaHR), defined as complete hematologic response (CHR) or no evidence of leukemia (NEL). AP patients in MaHR are not eligible for this study. For CML patients in BP at study entry or Ph+ ALL patients: MaHR, consisting of CHR or NEL. BP and Ph+ ALL patients in MaHR are not eligible for this study.

Outcome Time Frame:

up to 24 months after first dose

Safety Issue:

No

Authority:

United States: Food and Drug Administration

Study ID:

AP24534-10-201

NCT ID:

NCT01207440

Start Date:

September 2010

Completion Date:

October 2020

Related Keywords:

  • Chronic Myeloid Leukemia (CML)
  • Ph+ Acute Lymphoblastic Leukemia (ALL)
  • CML
  • ALL
  • PH
  • ponatinib
  • PACE
  • Ph+ ALL
  • Leukemia
  • Leukemia, Lymphoid
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma
  • Leukemia, Myeloid
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive

Name

Location

UCLA Ronald Reagan Medical Center, Site #027Los Angeles, California  90095
H. Lee Moffitt Cancer Center & Research Institute, Site #017Tampa, Florida  33612
Emory Winship Cancer Institute, Site # 058Atlanta, Georgia  30322
The University of Chicago, Site # 001Chicago, Illinois  60637
Northwestern University Feinberg School of Medicine, Site # 023Chicago, Illinois  60611
University of Maryland, Greenebaum Cancer Center, Site # 040Baltimore, Maryland  21201
Dana-Farber Cancer Institute , Site # 008Boston, Massachusetts  02115
University of Michigan Medical Center, Site # 011Ann Arbor, Michigan  48109
Karmanos Cancer Institute, Site # 034Detroit, Michigan  48201
Washington University School of Medicine, Site # 007St. Louis, Missouri  63110-1093
Nebraska Hematology-Oncology, PC, Site #133Lincoln, Nebraska  68506
Northern New Jersey Cancer Associates, Site #128Hackensack, New Jersey  07601
Roswell Park Cancer Institute, Site #029Buffalo, New York  14263
Weill Medical College of Cornell University, Site #006New York, New York  10065
Memorial Sloan-Kettering Cancer Center, Site #078New York, New York  10065
Duke University Medical Center, Site #003Durham, North Carolina  27710
Oregon Health and Sciences University, Site #048Portland, Oregon  97239-3098
Jeanes Hospital of Temple University Health System, Site # 127Philadelphia, Pennsylvania  19111
MD Anderson Cancer Center, Site # 005Houston, Texas  77030
Huntsman Cancer Institute at the University of Utah, Site #043Salt Lake City, Utah  84112
Fred Hutchinson Cancer Research Center, Site #100Seattle, Washington  98109