CC-4047 in Treating Patients With Myelofibrosis

Mayo Clinic

Status and phase

Completed

Phase 2

Phase 1

Conditions

Secondary Myelofibrosis

Chronic Myeloproliferative Disorders

Treatments

Drug: CC-4047

Study type

Interventional

Funder types

Other

NIH

Identifiers

NCT00669578

MC078B (Other Identifier)

P30CA015083 (U.S. NIH Grant/Contract)

PO-MMM-PI-0007 (Other Identifier)

NCI-2009-01331 (Registry Identifier)

07-005317 (Other Identifier)

Details and patient eligibility

About

RATIONALE: Biological therapies, such as CC-4047, may stimulate the immune system in different ways and stop cancer cells from growing. CC-4047 may also stop the growth of cancer cells by blocking blood flow to the cancer.

PURPOSE: This trial is studying the side effects and best dose of CC-4047 and to see how well it works in treating patients with myelofibrosis.

Full description

OBJECTIVES:

Phase I:

Primary

To determine the Maximum Tolerated Dose of CC-4047 in the treatment of Primary, Post Polycythemia Vera, or Post Essential Thrombocythemia Myelofibrosis (PMF, post-PV MF, or post-ET MF).

Phase II:

Primary

Best overall response as determined by International Working Group Criteria over the first 6 cycles (168 days) of study treatment.

Secondary

Safety (type, frequency, severity [National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 3.0] of adverse events (AEs), and relationship of AEs to CC-4047.
Duration of response.
Time to response.
Best overall response as determined by International Working Group Criteria over the first 12 cycles (336 days) of study treatment.

OUTLINE: Patients receive oral CC-4047. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed at 28 days and then every 6 months for up to 3 years.

Enrollment

77 patients

Sex

All

Ages

18 to 120 years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion criteria

DISEASE CHARACTERISTICS:

Diagnosis of primary and post essential thrombocythemia (ET) or post polycythemia vera (PV) myelofibrosis requiring therapy
- De novo presentation (i.e., agnogenic myeloid metaplasia AND post ET or post PV myelofibrosis)
- Developed after an antecedent history of PV (i.e., post polycythemic myeloid metaplasia) or essential polycythemia (i.e., post thrombocythemic myeloid metaplasia)
Total hemoglobin < 10 g/dL OR transfusion dependent anemia (defined by a history of ≥ 2 units of red blood cell (RBC) transfusions within the past 28 days for hemoglobin < 8.5 g/dL that was not associated with overt bleeding) OR marked splenomegaly (e.g., ≥ 10 cm below costal margin)

PATIENT CHARACTERISTICS:

Eastern Cooperative Oncology Group (ECOG) performance status 0-2
Absolute neutrophil count (ANC) ≥ 500/μL
Platelet count ≥ 20,000/μL
Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT) ≤ 3 times upper limit of normal (ULN) (≤ 5 times ULN if attributed to hepatic extramedullary hematopoiesis)
Total bilirubin ≤ 3 times ULN OR direct bilirubin ≤ 2 times ULN
Serum creatinine ≤ 2.0 mg/dL
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective double-method contraception for ≥ 28 days before, during, and for ≥ 28 days after completion of study treatment
Agrees to abstain from donating blood, semen, or sperm during and for ≥ 28 days after completion of study treatment
Willing to undergo transfusion of blood products (if applicable)
Able to complete questionnaire(s) alone or with assistance
No known HIV positivity, hepatitis B carrier, or active hepatitis C infection
No serious medical condition, psychiatric illness, or any other condition, including the presence of laboratory abnormalities, that (as judged by the treating physician) would preclude giving informed consent or participating in the study or confound the ability to interpret data from the study
No other active malignancies, except basal cell or squamous cell carcinoma of the skin or carcinoma in situ of the cervix or breast
No active deep vein thrombosis or pulmonary embolism that has not been therapeutically anticoagulated

PRIOR CONCURRENT THERAPY:

Recovered from all prior therapy
No prior CC-4047
More than 28 days since prior growth factors, cytotoxic chemotherapeutic agents (e.g., hydroxyurea or anagrelide), corticosteroids, or experimental drugs or therapies
No other concurrent experimental drugs or therapies or cytotoxic chemotherapeutic agents (e.g., hydroxyurea or anagrelide) for myelofibrosis
No concurrent growth factors (including erythropoietin) for myelofibrosis, except G-CSF or pegfilgrastim
No concurrent chronic use (i.e., > 2 weeks) of more than physiologic doses of corticosteroids (dose equivalent to > 10 mg/day of prednisone)