Evaluation of CEP-701, an Orally Available JAK2 Tyrosine Kinase Inhibitor, as a Therapy for Patients With Myelofibrosis
18 Years
N/A
Both
Leukemia, Myelofibrosis
Trial Information
Evaluation of CEP-701, an Orally Available JAK2 Tyrosine Kinase Inhibitor, as a Therapy for Patients With Myelofibrosis
The Study Drug:
CEP-701 is designed to help prevent a certain type of molecule (called a mutated JAK2
receptor) that is found on myelofibrosis cells from sending continuous chemical signals that
lead to the growth of cancer cells.
Study Treatment:
If you are found to be eligible to take part in this study, you will take CEP-701 by mouth
(in liquid form) 2 times a day (once in the morning and once in the evening) every day in
30-day repeating cycles. You should take each dose about 12 hours apart.
The study doctor or nurse will teach you and/or a caregiver or family member how to prepare
each dose of the study drug, as well as how much should be taken each time. At each study
visit, you will be supplied with enough syringes, dosing cups, and study drug to last until
your next study visit. For each dose, you will use the syringe to draw the proper amount of
CEP-701. You will add the entire contents of the syringe to an approved juice in 1 of the
provided dosing cups. You should also drink an additional dosing cup of juice after taking
the drug dose. The following juices (100% juice only) are approved for use with CEP-701:
grape, pineapple, apple, V8 vegetable juice, and orange juice.
The study drug mixture may be stored (in an areas that are protected from light, such as in
a cabinet) for up to 1 hour at room temperature and up to 8 hours refrigerated (at about
35°F to 45 °F). If you miss a dose, you should not take another dose until your next
scheduled dose.
Study Visits:
You will initially have study visits at M. D. Anderson once a month. You will need to return
monthly for 6 months, then every 3 months if there are no side effects during the previous 3
cycles. After 2 years of therapy, your visits can be extended to every 6 months. After 6
cycles you may have either a study visit or a phone call from a member of study staff. If
you have a phone call, you will be asked how you are feeling, if you have experienced any
side effects since your last visit, and your blood tests will be reviewed with you. During
most study visits, you will have the following tests:
- You will have a physical exam.
- You will be asked how you are feeling and about any side effects you may have
experienced since your last visit.
- You will have blood (about 2 tablespoons) drawn to check your kidney and liver function
and blood cell count. This will be done every 2 weeks up to 3 months, then every 1-2
months.
- You will have a bone marrow/aspirate once every 3-6 months to see if you are responding
to treatment. After 2 years of therapy, this can be extended to every 12 months.
Length of Study:
You will continue on this study for at least 6 months to allow time for response. If you do
respond to study treatment, you may continue to receive cycles for up to 5 years.
If you do not respond to study treatment within 6 months, if the disease gets worse, if
intolerable side effects occur, if you have an illness that keeps you from taking the study
drug, or your doctor thinks it is in your best interest to stop taking part in this study,
you will be taken off this study.
This is an investigational study. CEP-701 is not Food and Drug Administration (FDA)
approved or commercially available. At this time, it is being used for research purposes
only in this study. Up to 41 patients will take part in this study. All will be enrolled at
M. D. Anderson.
Inclusion Criteria:
- Patients with Chronic Idiopathic Myelofibrosis (CIMF) requiring therapy, including
those 1) previously treated by CIMF-directed therapy and relapsed, intolerant, or
refractory to therapy; or 2) if newly diagnosed then with intermediate or high risk
according to Lille scoring system (adverse prognostic factors are: Hb < 10 g/dl, WBC
< 4 or > 30 x 10^9/L; risk group: 0 = low, 1 = intermediate, 2 = high), or with
symptomatic spleen that is >/= 10cm below costal margin. However, patients with
asymptomatic intermediate risk disease are not eligible.
- JAK2 mutation positive test
- Age of at least 18 years
- Eastern Cooperative Oncology Group (ECOG) performance status 0-2
- Adequate liver and renal function: total bilirubin aminotransferase (ALT or SGPT) and creatinine
- Patients must be at least 2 weeks from prior chemotherapy, biological therapy,
radiation therapy, major surgery, or other investigational anticancer therapy that is
considered MF-directed, and have recovered from prior toxicities to Grade 0-1.
Concurrent therapy with supportive care medications (hydroxyurea, anagrelide) is
allowed during the study.
- All men of reproductive potential and women of child-bearing potential (WOCBP) must
agree to practice effective contraception (iud, birth control pill, latex condoms,
diaphragm) during the entire study period and for one month after the study ends,
unless documentation of infertility exists. Should a woman become pregnant or suspect
she is pregnant while participating in this study, she should inform her treating
physician immediately. WOCBP are women who are not menopausal for 12 months or no
previous surgical sterilization."
- Ability to understand and willingness to sign the informed consent form
- Not willing to undergo, not a candidate for, or not having a donor for, a bone marrow
transplant
Exclusion Criteria:
- Pregnant or nursing women, due to the unknown effects of therapy on the developing
fetus or newborn infant.
- Patients diagnosed with another malignancy - unless following curative intent therapy
the patient has been disease free for at least 3 years. Patients with early stage
squamous cell carcinoma of the skin, basal cell carcinoma of the skin, or cervical
intraepithelial neoplasia (CIN) are eligible for this study
- Any condition, including serious medical condition, laboratory abnormality, or
psychiatric illness, which places the subject at unacceptable risk as judged by the
Principal Investigator, if he/she was to participate in the study
- Known positive for Human immunodeficiency virus (HIV) or infectious hepatitis, type
A, B or C
- Presence of any gastrointestinal condition or concomitant medication use (e.g.
coumadin) that would render a patient at high risk for gastrointestinal bleeding as
judged by treating physician
- History of any upper or lower gastrointestinal bleeding in the 6 months prior to
enrollment
- Elevated international normalized ratio (INR) or Partial thromboplastin time (PTT)
Type of Study:
Interventional
Study Design:
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Number of Participants With Objective Response
Outcome Description:
Objective response = Complete Response, absence sign/symptoms of disease (without use of growth factors, hydroxyurea, anagrelide, or transfusions for > 1 month); Partial Response, absence of progressive disease (PD), and improvement in 2+ parameters (if abnormal): Absolute neutrophil count (ANC), hemoglobin, platelets, transfusions, splenomegaly, or bone marrow blasts; Clinical Improvement, absence of PD, and improvement in 1 parameter: ANC, hemoglobin, platelets, transfusions, splenomegaly, or bone marrow blasts). [International Working Group on Myelofibrosis Research and Treatment]
Outcome Time Frame:
Response assessed after each 3 cycles (cycle = 30 days)
Safety Issue:
No
Principal Investigator
Srdan Verstovsek, M.D.
Investigator Role:
Principal Investigator
Investigator Affiliation:
M.D. Anderson Cancer Center
Authority:
United States: Food and Drug Administration
Study ID:
2007-0070
NCT ID:
NCT00494585
Start Date:
June 2007
Completion Date:
May 2010
Related Keywords:
- Leukemia
- Myelofibrosis
- CEP-701
- Leukemia
- Myelofibrosis
- MF
- JAK2
- Tyrosine Kinase Inhibitor
- Lestaurtinib
- Chronic Idiopathic Myelofibrosis
- CIMF
- Primary Myelofibrosis
- Leukemia
Name | Location |
|---|---|
| The University of Texas M.D. Anderson Cancer Center | Houston, Texas |
