Lenalidomide for Patients With Myelofibrosis (MF)

Condition(s) targeted: Myelofibrosis

Intervention: lenalidomide + Prednisone (Drug)

Phase: Phase 2

Status: Active, not recruiting

Sponsored by: M.D. Anderson Cancer Center

Official(s) and/or principal investigator(s):
Srdan Verstovsek, MD, Principal Investigator, Affiliation: M.D. Anderson Cancer Center

The goal of this clinical research study is to learn if lenalidomide in combination with prednisone can help to control myelofibrosis. The safety of lenalidomide and prednisone for the treatment of myelofibrosis will also be studied.

Official title: Evaluation of Lenalidomide (CC-5013) and Prednisone as a Therapy for Patients With Myelofibrosis (MF)

Study design: Treatment, Non-Randomized, Open Label, Historical Control, Single Group Assignment, Safety/Efficacy Study

Primary outcome: To determine the efficacy of lenalidomide and prednisone in combination in patients with MF, in achieving objective improvements in disease status: complete and partial response, and hematological improvement.

Secondary outcome: To determine the safety of lenalidomide and prednisone in combination, in patients with MF and to examine pertinent morphological, biological, and molecular characteristics of MF.

Detailed description: Myelofibrosis with myeloid metaplasia (MF) is a rare clonal proliferative disorder of a pluripotent stem cell. MF can be either primary process or representative of end-stage myeloproliferative diseases such as polycythemia vera (PV) or essential thrombocythemia (ET).

The disease generally occurs in adults. In 40% of patients, constitutional symptoms are present including fever, weight loss, nocturnal sweating, pruritis, and bone pain. Splenomegaly is present in 85% to 100% at diagnosis. Hematologic disease features include anemia. Approximately half of the patients present with an elevated white cell count (WBC), 28% with thrombocytosis. Circulating blast cells are present in one-third of the patients.

No standard therapy exists for MF. No medical therapy has been proven to prolong overall survival. Patients with an intact quality of life and no threatening hematologic abnormalities have usually been considered to not require any therapy; however, new therapeutic modalities are currently being considered in determining treatment indications.

Lenalidomide is in a class of compounds known as IMiDs® with immunomodulatory and anti-angiogenic properties that could confer antitumor and antimetastatic effects. As a single agent it is effective in ~25% of MF patients, in improving cytopenias and reducing splenomegaly. Side effects included mainly rash and fatigue.

Steroid preparations are commonly used as therapy for MF. Furthermore, when used in combination with other medications they improve tolerance of those medications and improve results. While there is no experience with lenalidomide and steroids in combination, it is expected that the combination will improve the tolerance of lenalidomide with subsequent improvement in the results of therapy.

Optional Procedures: If you agree, you will have about 3-6 teaspoons of blood drawn before treatment starts. This will be done to see how lenalidomide works on the abnormal cells.

If you agree, you will also have about 2 teaspoons of bone marrow taken before treatment starts, and then every 3 months while you are on study. This will be done to see how lenalidomide works on the abnormal cells.

All optional blood and bone marrow samples will be collected at the same time as normal tests.

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

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

Inclusion Criteria:

- Diagnosis of myelofibrosis requiring therapy, including those previously treated and

relapsed or refractory, or if newly diagnosed, with intermediate or high risk according to Lille scoring system (risk factors are: Hb < 10 g/dl, WBC < 4 or > 30 x 109/L; risk group: 0 factor(s) = low, 1 factor(s) = intermediate, 2 factor(s) = high) or with symptomatic splenomegaly

- Understanding and voluntary signing an IRB-approved informed consent form.

- Age >/= 18 years at the time of signing the informed consent.

- Disease-free of prior malignancies for >/= 2-years with exception of basal cell or

squamous cell carcinoma of the skin, or carcinoma "in situ" of the cervix or breast.

- ECOG performance status 0 to 2.

- Patients must have adequate organ function as demonstrated by the following: Total

bilirubin /= 1 x 10^9/L; ALT - Women of child bearing potential must have 2 negative pregnancy tests (sensitivity of

at least 50 mIU/mL). The first 10-14 days prior to starting therapy and the second negative pregnancy test within 24 hours of start of therapy. Women of child bearing potential must have birth control plan (2 methods of approved contraception) in effect for at least 4 weeks prior to the initiation of therapy, and must be willing to use 2 methods of approved contraception throughout the study and for 30 days after the last dose of lenalidomide.

- In addition, men must be willing to use a latex condom if sexually active with a woman

of child bearing potential during treatment and for 30 days after the last dose, even if they have had a successful vasectomy.

Exclusion Criteria:

- Use of any other standard (e. g. hydroxyurea, anagrelide, growth factors) or

experimental drug or therapy within 28 days of starting lenalidomide and/or lack of recovery from all toxicity from previous therapy to grade 1 or better.

- Known prior clinically relevant hypersensitivity reaction to thalidomide, including

the development of erythema nodosum if characterized by a desquamating rash.

- Prior therapy with lenalidomide.

- Any serious medical condition, laboratory abnormality, or psychiatric illness that

would prevent the subject from signing the informed consent form.

- Pregnant or lactating females.

- Any condition, including the presence of laboratory abnormalities, which places the

subject at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study.

- Known positive for HIV or infectious hepatitis, type A, B or C.

- Known prior clinically relevant hypersensitivity to prednisone.

- Participants with a heart rate (HR) of less than or equal to 50, as a HR less than 50

indicates underlying cardiac abnormalities.

- Participants with prior history of thromboembolic disease (i. e.-deep venous thrombosis

[DVT] or pulmonary embolism [PE]) within the last six months, as Lenalidomide has demonstrated a significantly increased risk of DVT or PE.

The University of Texas M.D. Anderson Cancer Center, Houston, Texas 77030, United States

M.D. Anderson's website

Starting date: July 2006
Ending date: July 2009
Last updated: December 10, 2007