Basic Trial Information
Trial Description
     Summary
     Further Trial Information
     Eligibility Criteria
Trial Contact Information

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase II Treatment Active 18 and over Other 2007-0070 CS-2007-20040, NCT00494585

Trial Description

Summary

The goal of this clinical research study is to find out if CEP-701 can help control MF. The safety of CEP-701 will also be studied.

Further Study Information

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.

Screening Tests Before you can start treatment on this study, you will have "screening tests." These tests will help the study doctor decide if you are eligible to take part in this study.

You will have a physical exam, including measurement of your vital signs (blood pressure, heart rate, temperature, and breathing rate).

You will have a bone marrow biopsy/aspirate performed. To collect a bone marrow biopsy/aspirate, an area of the hip or chest bone is numbed with anesthetic, and a small amount of bone marrow and bone is withdrawn through a large needle.

Blood (about 2 teaspoons) will be drawn for tests to check your kidney and liver function.

Women who are able to have children must have a negative urine or blood (about 1 tablespoon) pregnancy test.

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.

Additional Information You will be given a medication diary to write down what time you take each dose. You will need to bring the diary with you to each study visit. If your dose is lowered because of side effects, a new copy of the diary will be given to you at the next study visit. Also, you will need to return all used and unused study drug at each visit.

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 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.

You will have a bone marrow/aspirate once every 3 months to see if you are responding to treatment.

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 2 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 FDA approved or commercially available. At this time, it is being used for research purposes only in this study. You will not have to pay for taking the study drug (along with the supplies) while you are on this study. Up to 41 patients will take part in this study. All will be enrolled at M. D. Anderson.

Optional Procedures: If you agree, you will have extra blood drawn (about 1 tablespoon) for testing so that researchers can see how CEP-701 affects the disease. It will be drawn before treatment starts, then once a month up to 3 months, and then once every 3 months. Your blood will be collected during the same time you are having routine blood tests.

You will not have to pay for taking part in the optional procedures.

You do not have to agree to take part in the optional procedures in order to receive treatment on this study.

Eligibility Criteria

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 </=2.0 mg/dL, alanine aminotransferase (ALT or SGPT) </=2.0 x institutional upper limit of normal (ULN), and creatinine </=2.0 mg/dl

• 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 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 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 INR or PTT

Trial Contact Information

Trial Lead Organizations/Sponsors

M. D. Anderson Cancer Center at University of Texas

Srdan Verstovsek

Principal Investigator

Srdan Verstovsek, M.D.		Ph: 713-745-3429
		Email: sverstov@mdanderson.org

U.S.A.
Texas
	Houston
	M. D. Anderson Cancer Center at University of Texas
		Srdan Verstovsek, M.D.	Ph: 713-745-3429
			Email: sverstov@mdanderson.org
		Srdan Verstovsek, M.D.	Principal Investigator

Link to the current ClinicalTrials.gov record.
NLM Identifer NCT00494585
Information obtained from ClinicalTrials.gov on July 16, 2008