CEP-701 for PH-negative Myelofibrosis

• Sponsor: M.D. Anderson Cancer Center (Other)
• Overall Status: Completed
• CT.gov ID: NCT00494585
• Collaborator: Cephalon (Industry)
• Enrollment: 27
• Location: 1
• Arm: 1
• Duration (Months): 35
• Patients Per Site Per Month: 0.8

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Leukemia; Myelofibrosis	Drug: CEP-701	Phase 2

Detailed Description

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 27 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Evaluation of CEP-701, an Orally Available JAK2 Tyrosine Kinase Inhibitor, as a Therapy for Patients With Myelofibrosis
• Study Start Date: Jun 1, 2007
• Actual Primary Completion Date: May 1, 2010
• Actual Study Completion Date: May 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: CEP-701 80 mg orally twice a day for 30 days	Drug: CEP-701; 80 mg orally twice a day for 30 days; Other Names: lestaurtinib

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Objective Response [Response assessed after each 3 cycles (cycle = 30 days)]

   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]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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 (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)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	The University of Texas M.D. Anderson Cancer Center	Houston	Texas	United States	77030

Sponsors and Collaborators

• M.D. Anderson Cancer Center
• Cephalon

Investigators

• Principal Investigator: Srdan Verstovsek, M.D., M.D. Anderson Cancer Center

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• M.D. Anderson's website

Publications

None provided.

• Responsible Party: M.D. Anderson Cancer Center
• ClinicalTrials.gov Identifier: NCT00494585
• Other Study ID Numbers: 2007-0070; CS-2007-20040
• First Posted: Jun 29, 2007
• Last Update Posted: Jun 25, 2012
• Last Verified: Jun 1, 2012

• Keywords provided by M.D. Anderson Cancer Center: CEP-701; Leukemia; Myelofibrosis; MF; JAK2; Tyrosine Kinase Inhibitor; Lestaurtinib; Chronic Idiopathic Myelofibrosis; CIMF
• Additional relevant MeSH terms: Primary Myelofibrosis

Study Results

Participant Flow

Recruitment Details	Recruitment Period: 6/28/2007 through 10/25/2007. All participants recruited at UT MD Anderson Cancer Center.
Pre-assignment Detail	Of the 27 participants registered, 5 participants were ineligible to participate.

Arm/Group Title	CEP-701
Arm/Group Description	80 mg orally twice daily for 30 days
Period Title: Overall Study
STARTED	22
COMPLETED	22
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	CEP-701
Arm/Group Description	80 mg orally twice daily for 30 days
Overall Participants	22
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	61
Sex: Female, Male (Count of Participants)
Female	6 27.3%
Male	16 72.7%
Region of Enrollment (participants) [Number]
United States	22 100%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Objective Response
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]
Time Frame	Response assessed after each 3 cycles (cycle = 30 days)

Outcome Measure Data

Analysis Population Description

Intention to treat.

Arm/Group Title	CEP-701
Arm/Group Description	80 mg orally twice daily for 30 days
Measure Participants	22
Complete Response (CR)	0 0%
Partial Response (PR)	0 0%
Clinical Improvement (CI)	6 27.3%

Adverse Events

Time Frame	3 years 10 months
Arm/Group Title	CEP-701
Arm/Group Description	80 mg orally twice daily for 30 days
All Cause Mortality
	CEP-701
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	CEP-701
	Affected / at Risk (%)	# Events
Total	7/22 (31.8%)
Blood and lymphatic system disorders
Hematoma	1/22 (4.5%)	1
Hemorrhage	1/22 (4.5%)	1
General disorders
Debridement surgery with VAC placement	1/22 (4.5%)	1
Death	4/22 (18.2%)	4
Dehydration	1/22 (4.5%)	1
Infections and infestations
Infection	1/22 (4.5%)	1
Respiratory, thoracic and mediastinal disorders
Chronic Interstitial Pulmonary Fibrosis	1/22 (4.5%)	1
Other (Not Including Serious) Adverse Events
	CEP-701
	Affected / at Risk (%)	# Events
Total	19/22 (86.4%)
Blood and lymphatic system disorders
Anemia	6/22 (27.3%)	6
Thrombocytopenia	5/22 (22.7%)	5
Gastrointestinal disorders
Diarrhea	16/22 (72.7%)	16
Nausea	11/22 (50%)	11
Vomiting	6/22 (27.3%)	6
Flatulence	5/22 (22.7%)	5
Heartburn	4/22 (18.2%)	4
Mucositis	3/22 (13.6%)	3
Anorexia	2/22 (9.1%)	2
General disorders
Fatigue	2/22 (9.1%)	2
Hepatobiliary disorders
Elevated aspartate aminotransferase	6/22 (27.3%)	6
Elevated alanine aminotransferase	6/22 (27.3%)	6
Elevated alkaline phosphatase	2/22 (9.1%)	2
Hyperbilirubinemia	2/22 (9.1%)	2
Nervous system disorders
Headache	7/22 (31.8%)	7
Peripheral Neuropathy	3/22 (13.6%)	3

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.