CEP-701 (Lestaurtinib) in Myelofibrosis

NCT ID: NCT00668421

Last Updated: 2014-11-26

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

UNKNOWN

Clinical Phase

PHASE1/PHASE2

Total Enrollment

60 participants

Study Classification

INTERVENTIONAL

Study Start Date

2008-04-30

Study Completion Date

2015-01-31

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

Myelofibrosis is the gradual replacement of bone marrow (place where most new blood cells are produced) by fibrous tissue which reduces the body's ability to produce new blood cells and results in the development of chronic anemia (low red blood cell count). One of the main distinctions of myelofibrosis is "extramedullary hematopoesis", the migration or traveling of the blood-forming cells out of the bones to other parts of the body, such as the liver or spleen, resulting in an enlarged spleen and liver.

Treatment for myelofibrosis is unsatisfactory and there is no medication that is specifically used in the treatment of myelofibrosis. There is a protein that is found to be present in the majority of myelofibrosis patients (JAK2) and the drug Lestaurtinib is being studied to see if it will stop this protein from functioning and thereby help control the disease.

This study is divided into two Phases (1 \& 2). In phase 1 we will be looking for the dose of study medication (Lestaurtinib) that will be the highest dose a patient can take without experiencing serious side effects, maximum tolerated dose (MTD).

In phase 2, after the MTD dose has been established in phase 1, we will be investigating how well CEP-701 (Lestaurtinib) works at suppressing the protein (JAK2).

The investigators also wish to find out important biologic characteristics or features of myelofibrosis through an additional correlative biomarker study (MPD-RC #107). The correlative biomarker study is a study that is related to the main study, but is looking to answer different questions than the main study. The purpose of the biomarker study is to understand the causes of MPD and to develop improved methods for the diagnosis and treatment of these diseases, while the main study is trying to find out how well CEP-701 (Lestaurtinib) will work in treating the myeloproliferative disease.

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Myelofibrosis Essential Thrombocythemia Polycythemia Vera

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

CEP-701 (Lestaurtinib)

Subject is to receives Lestaurtinib, in Phase 1: standard cohort dose escalation; Phase 2: single stage design to estimate the percentage of subjects with a 15% or greater reduction in JAK2 V617F allele frequency in peripheral blood granulocytes in 6 months of treatment

Group Type EXPERIMENTAL

CEP-701 (Lestaurtinib)

Intervention Type DRUG

Lestaurtinib (CEP-701), oral formulation. Phase 1: 80 BID - 160 BID; phase 2: 140 mg

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

CEP-701 (Lestaurtinib)

Lestaurtinib (CEP-701), oral formulation. Phase 1: 80 BID - 160 BID; phase 2: 140 mg

Intervention Type DRUG

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

1. Diagnosis of primary myelofibrosis, essential thrombocythemia related myelofibrosis, or polycythemia vera related myelofibrosis requiring therapy, including:

1. those previously treated and relapsed or refractory
2. or newly diagnosed, with intermediate or high risk according to Lille Scoring system (adverse prognostic factors are: Hb \< 10 g/dl, WBC \< 4 or \> 30 x 109/L; risk group: 0 = low, 1 = intermediate, 2 = high)
3. or with symptomatic splenomegaly (must be \>=10 cm below the left costal margin in the mid-clavicular line).
2. The subject must not be considered as a candidate to receive allogeneic hematopoietic stem cell transplant at the time of being enrolled into the study.
3. The subject has a detectable JAK2 V617F mutation.
4. Signed informed consent: Patients must have signed consents for both the Lestaurtinib protocol and for the mandatory biomarker MDP-RC 107 protocol to be eligible to participate.
5. Patients must have been off any PMF-directed therapy for 4 weeks prior to entering this study and have recovered from the toxic effects (grade 0-1) of that therapy. Treatment with erythropoietin is permitted.
6. Serum bilirubin levels less than or equal to 2 times the upper limit of the normal range for the laboratory (ULN). Higher levels are acceptable if these can be attributed by treating physician to active hemolysis or ineffective erythropoiesis due to myelofibrosis.
7. Serum glutamic-pyruvic transaminase (SGPT) (alanine aminotransferase \[ALT\]) levels less than or equal to 2 x ULN.
8. Serum creatinine levels less than or equal to 1.5 x ULN.
9. Women of childbearing potential must have a negative serum or urine pregnancy test prior to Lestaurtinib treatment and should be advised to avoid becoming pregnant. Men must be advised to not father a child while receiving treatment with Lestaurtinib. Both women of childbearing potential and men must practice effective methods of contraception (those generally accepted as standard of care measures). Women of child bearing potential are women who are not menopausal for 12 months or who have not undergone previous surgical sterilization. If the subject is a woman of childbearing potential, she must use a medically acceptable form of contraception during the study period and for 30 days thereafter. If the subject is a man he must be surgically sterile or must use a medically approved method of contraception for the duration of the study and for 60 days following the last dose of CEP-701.
10. Age \> 18 years.

Exclusion Criteria

1. Nursing and pregnant females. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
2. New York Heart Association (NYHA) Grade II or greater congestive heart failure.
3. Unstable angina.
4. Major surgical procedure, open biopsy, or significant traumatic injury within 28 days, or anticipation of the need for major surgical procedure during the course of the study.
5. Biopsy or other minor surgical procedure, excluding placement of a vascular access device or bone marrow biopsy, within 7 days prior to study enrollment.
6. Ongoing serious, non-healing wound, ulcer, or bone fracture.
7. Known hypersensitivity to any component of Lestaurtinib.
8. The subject has received a donor stem cell transplant in the past and has detectable full or partial donor chimerism.
9. The subject requires treatment with a CYP3A4 inhibitor, including azole antifungals (topicals are permitted); protease inhibitors; nefazodone; cyclosporine; erythromycin; clarithromycin; and troleandomycin.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

Myeloproliferative Disorders-Research Consortium

NETWORK

Sponsor Role collaborator

National Cancer Institute (NCI)

NIH

Sponsor Role collaborator

Ronald Hoffman

OTHER

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Ronald Hoffman

Professor

Responsibility Role SPONSOR_INVESTIGATOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Ronald Hoffman, MD

Role: PRINCIPAL_INVESTIGATOR

Icahn School of Medicine at Mount Sinai

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

Palo Alto Medical Facilities

Palo Alto, California, United States

Site Status

Georgetown University Medicine Center

Washington D.C., District of Columbia, United States

Site Status

University of Maryland Marlene and Stewart Greenebaum Cancer Center

Baltimore, Maryland, United States

Site Status

Weill Cornell

Ithaca, New York, United States

Site Status

Icahn School of Medicine at Mount Sinai

New York, New York, United States

Site Status

University of Pennsylvania

Philadelphia, Pennsylvania, United States

Site Status

University of Utah

Salt Lake City, Utah, United States

Site Status

Countries

Review the countries where the study has at least one active or historical site.

United States

References

Explore related publications, articles, or registry entries linked to this study.

Hexner EO, Mascarenhas J, Prchal J, Roboz GJ, Baer MR, Ritchie EK, Leibowitz D, Demakos EP, Miller C, Siuty J, Kleczko J, Price L, Jeschke G, Weinberg R, Basu T, Pahl HL, Orazi A, Najfeld V, Marchioli R, Goldberg JD, Silverman LR, Hoffman R. Phase I dose escalation study of lestaurtinib in patients with myelofibrosis. Leuk Lymphoma. 2015;56(9):2543-51. doi: 10.3109/10428194.2014.1001986. Epub 2015 Feb 20.

Reference Type DERIVED
PMID: 25563429 (View on PubMed)

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

P01CA108671-01A2

Identifier Type: NIH

Identifier Source: secondary_id

View Link

MPD-RC 104

Identifier Type: OTHER

Identifier Source: secondary_id

GCO 07-0548-00104

Identifier Type: -

Identifier Source: org_study_id