| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated | | Myelofibrosis with myeloid metaplasia | |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 9.1 | | E.1.2 | Level | LLT | | E.1.2 | Classification code | 10028538 | | E.1.2 | Term | Myelofibrosis with myelometaplasia | |
| E.1.3 | Condition being studied is a rare disease | Yes |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial | | •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. | |
| E.2.2 | Secondary objectives of the trial | | •To determine the safety of CC-4047 as single-agent and in combination with prednisone in the treatment of myelofibrosis with myeloid metaplasia. | |
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal 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, pregnancy testing must occur weekly for the first 28 days and then every 14 days while on study, at study discontinuation, and at days 14 and 28 following discontinuation from study.
•In addition to the required pregnancy testing, the Investigator must confirm with FCBP that she is continuing to use 2 reliable methods of birth control at each visit.
•Counseling about pregnancy precautions and the potential risks of fetal exposure must be conducted at a minimum of every 28 days. During counseling, subjects must be reminded to not share study drug and to not donate blood.
•Pregnancy testing and counseling must be performed if a subject misses her period or if her pregnancy test or her menstrual bleeding is abnormal. Study drug treatment must be discontinued during this evaluation.
•Females must agree to abstain from breastfeeding during study participation and for at least 28 days after discontinuation from study.
Male Subjects:
•Counseling about the requirement for latex condom use during sexual contact with FCBP and the potential risks of fetal exposure must be conducted at a minimum of every 28 days. During counseling, subjects must be reminded to not share study drug and to not donate blood, sperm, or semen.
11.If pregnancy or a positive pregnancy test does occur in a study subject or partner of a male study subject during study participation, study drug must be immediately discontinued. | |
| E.4 | Principal 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 or, 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.
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.
| |
| E.5 End points |
| E.5.1 | Primary end point(s) | | •Best overall response as determined by International Working Group Criteria over the first 6 cycles (168 days) of study treatment | |
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | No |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | No |
| E.6.6 | Pharmacokinetic | No |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | Yes |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| E.8.1.5 | Parallel group | Yes |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | Yes |
| E.8.2.2 | Placebo | Yes |
| E.8.2.3 | Other | No |
| E.8.3 | The trial involves single site in the Member State concerned | Yes |
| E.8.4 | The trial involves multiple sites in the Member State concerned | No |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 6 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned | |
| E.8.7 | Trial has a data monitoring committee | Yes |
| E.8.8 | Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial | |
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 1 |
| E.8.9.1 | In the Member State concerned months | 4 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial years | 1 |
| E.8.9.2 | In all countries concerned by the trial months | 4 |
