A PHASE 2, PROSPECTIVE, RANDOMIZED, MULTICENTER, DOUBLE-BLIND, ACTIVE- CONTROL, PARALLEL-GROUP STUDY TO DETERMINE THE SAFETY OF AND TO SELECT A TREATMENT REGIMEN OF CC-4047 EITHER AS SINGLE-AGENT OR IN COMBINATION WITH PREDNISONE TO STUDY FURTHER IN SUBJECTS WITH MYELOFIBROSIS WITH MYELOID METAPLASIA

• Register: EUCTR
• Last refreshed on: 2 December 2013
• Main ID: EUCTR2006-004553-17-AT
• Date of registration: 27/02/2007
• Prospective Registration: No
• Primary sponsor: Celgene Corporation
• Public title: A PHASE 2, PROSPECTIVE, RANDOMIZED, MULTICENTER, DOUBLE-BLIND, ACTIVE- CONTROL, PARALLEL-GROUP STUDY TO DETERMINE THE SAFETY OF AND TO SELECT A TREATMENT REGIMEN OF CC-4047 EITHER AS SINGLE-AGENT OR IN COMBINATION WITH PREDNISONE TO STUDY FURTHER IN SUBJECTS WITH MYELOFIBROSIS WITH MYELOID METAPLASIA
• Scientific title: A PHASE 2, PROSPECTIVE, RANDOMIZED, MULTICENTER, DOUBLE-BLIND, ACTIVE- CONTROL, PARALLEL-GROUP STUDY TO DETERMINE THE SAFETY OF AND TO SELECT A TREATMENT REGIMEN OF CC-4047 EITHER AS SINGLE-AGENT OR IN COMBINATION WITH PREDNISONE TO STUDY FURTHER IN SUBJECTS WITH MYELOFIBROSIS WITH MYELOID METAPLASIA
• Date of first enrolment: 19/02/2007
• Target sample size: 80
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2006-004553-17
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: yes Placebo: yes Other: no

Countries of recruitment

Austria, Germany, Italy, Spain, United Kingdom

Key inclusion & exclusion criteria

Inclusion criteria:
1.=18 years old at time of signed informed consent.
2.Diagnosed with myelofibrosis requiring therapy including myelofibrosis with myeloid metaplasia.
3.Eligibility is based on local review of bone marrow aspirate and biopsy.
4.Screening total Hb level <10g/dL or transfusion-dependent anemia defined as per IWG criteria.
5.Adequate organ function as demonstrated by the following = 14 days prior to starting study drug:
•ALT (SGPT)/AST (SGOT) =3x upper limit of normal (ULN) [unless treating physician believes this is due to extramedullary hematopoiesis].
•Total Bilirubin <3x ULN or Direct Bilirubin <2x ULN
•Serum creatinine =2.0 mg/dL
•Absolute neutrophil count =1,000/µL (=1 x 109/L)
•Platelet count =50,000 /µL (=50 x 109/L)
6.Willing to receive transfusion of blood products
7.ECOG performance status of 0-2 at screening.
8.Able to adhere to study visit schedule and other protocol requirements.
9.No active malignancies with exception of controlled prostate cancer , basal cell or squamous cell carcinoma of the skin, or carcinoma “in situ” of the cervix or breast.
10.Females of childbearing potential (FCBP) must agree to use 2 reliable forms of contraception simultaneously or to practice complete abstinence from heterosexual intercourse during the following time periods related to the study:1) for at least 28 days before starting study drug; 2)while participating in study; 3) for at least 28 days after discontinuation from study. The 2 methods of reliable contraception must include 1 highly effective method (ie intrauterine device [IUD], hormonal [birth control pills, injections, or implants], tubal ligation, or partner’s vasectomy) and 1 additional effective (barrier) method (ie latex condom, diaphragm, cervical cap). FCBP must be referred to a qualified provider of contraceptive methods if needed.
Before starting study drug:
Female Subjects:
•FCBP must have 2 negative pregnancy tests (sensitivity of at least 50mIU/mL) prior to starting study drug, the first of which must be performed within 10-14 days prior to start of study drug and the second performed within 24 hours prior to start of study drug. The subject may not receive study drug until the Investigator has verified that the results of these pregnancy tests are negative.
•Will be warned that sharing study drug is prohibited and will be counseled about pregnancy precautions and potential risks of fetal exposure.
•Must agree to abstain from donating blood during study participation and for at least 28 days after discontinuation from study.
Male Subjects:
•Must agree to use a latex condom during sexual contact with FCBP while participating in study and for at least 28 days following discontinuation from study even if he has undergone a successful vasectomy.
•Will be warned that sharing study drug is prohibited and will be counseled about pregnancy precautions and potential risks of fetal exposure.
•Must agree to abstain from donating blood, semen, or sperm during study participation and for at least 28 days after discontinuation from study.
During study participation and for 28 days following discontinuation from the study:
All Subjects:
•No more than a 28-day supply of study drug will be dispensed at a time.
Female Subjects:
•FCBP with regular cycles must agree to have pregnancy tests weekly for the first 28 days of study participation and then every 28 days while on study, at study discontinuation, and at day 28 following discontinuation from study. If menstrual cycles are irregular,
Exclusion criteria:
1.Known positive status for HIV, hepatitis B carrier, or active hepatitis C infection.
2.Previous untoward reaction to corticosteroid (specifically, prednisone) therapy that was severe enough, in the opinion of the treating physician, to preclude study participation.
3.The use of any growth factors, cytotoxic chemotherapeutic agents (e.g. hydroxyurea and anagrelide), corticosteroids, or experimental drug or therapy within a minimum of 28 days of starting CC-4047 and/or lack of recovery from all toxicity from previous therapy to grade 1 or better (e.g. alpha interferon may require 84 days or longer for washout).
4.Prior therapy with CC-4047, lenalidomide or thalidomide for MMM. (Prior prednisone use as a therapy for MMM is allowed, but not within 28 days of starting CC-4047).
5.History of deep vein thrombosis or pulmonary embolism within one year of starting study medication.
6.Any serious medical condition or psychiatric illness that would prevent, (as judged by the treating physician) the subject from signing the informed consent form or 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.
7.Pregnant or lactating females.



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Myelofibrosis with myeloid metaplasia
MedDRA version: 14.1 Level: LLT Classification code 10028538 Term: Myelofibrosis with myelometaplasia System Organ Class: 100000004864

Intervention(s)

Product Code: CC-4047
Pharmaceutical Form: Capsule
CAS Number: 19171-19-8
Current Sponsor code: CC-4047
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 0.5-
Pharmaceutical form of the placebo: Capsule
Route of administration of the placebo: Oral use

Product Code: CC-4047
Pharmaceutical Form: Capsule
CAS Number: 19171-19-8
Current Sponsor code: CC-4047
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 1.0-
Pharmaceutical form of the placebo: Capsule
Route of administration of the placebo: Oral use

Product Name: Prednisone
Product Code: H02 AB07
Pharmaceutical Form: Capsule
INN or Proposed INN: Prednisone
Concentration type: equal
Concentration number: 15-
Pharmaceutical form of the placebo: Capsule
Route of administration of the placebo: Oral use

Product Code: CC-4047 (NEW FORMULATION)
Pharmaceutical Form: Capsule
CAS Number: 19171-19-8
Current Sponsor code: CC-4047
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 0.5-

Product Code: CC-4047 (NEW FORMULATION)
Pharmaceutical Form: Capsule
CAS Number: 19171-19-8
Current Sponsor code: CC-4047
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 1.0-

Primary Outcome(s)

Secondary Objective: •To determine the safety of CC-4047 as single-agent and in combination with prednisone in the treatment of myelofibrosis with myeloid metaplasia.

Primary end point(s): •Best overall response as determined by International Working Group Criteria over the first 6 cycles (168 days) of study treatment

Main Objective: •To select a treatment regimen of CC-4047 either as single-agent or in combination with prednisone to study further in subjects with myelofibrosis with myeloid metaplasia.

Secondary ID(s)

CC-4047-MMM-001

2006-004553-17-GB