Clinical trial NCT00669578: CC-4047 in Treating Patients With Myelofibrosis
Official title: A Phase I/II, Prospective, Open-Label Study to Determine the Safety and Efficacy of CC-4047 in Patients With Primary, Post Polycythemia Vera, or Post Essential Thrombocythemia Myelofibrosis®
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Chronic Myeloproliferative Disorders
Secondary Myelofibrosis
Keywords: secondary myelofibrosis
polycythemia vera
essential thrombocythemia
primary myelofibrosis
Lead sponsor: Mayo Clinic
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2008-04-30
Enrollment: 77
Sex: ALL
Minimum age (years): 18
Maximum age (years): 120
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

Detailed 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.

Eligibility 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)

Primary outcomes:
measure: Determine the Maximum Tolerated Dose of CC-4047
timeFrame: The first 28-day cycle of treatment.
measure: Best Overall Response Over the First 6 Cycles of Treatment
timeFrame: Every cycle of treatment for 6 cycles. Each cycle is 28 days.
Secondary outcomes:
measure: Number of Participants With Treatment Related Adverse Events.
timeFrame: During treatment and every 6 months until 3 years from registration or progression.
measure: Duration of Response Time
timeFrame: Time from response to disease progression, intolerance of study drug, or death.
measure: Time to Response
timeFrame: Time from registration to the first date of response within twelve 28-day cycles of treatment.
Other outcomes:
Locations:
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
Study officials:
affiliation: Mayo Clinic
name: Ruben A. Mesa, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Mayo Clinic
name: Ayalew Tefferi, MD
role: STUDY_CHAIR
References: