| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Refractory or relapsed and refractory multiple myeloma |
|
| E.1.1.1 | Medical condition in easily understood language |
| Refractory or relapsed and refractory multiple myeloma |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 16.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10028228 |
| E.1.2 | Term | Multiple myeloma |
| E.1.2 | System Organ Class | 100000004864 |
|
| 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 evaluate the efficacy of pomalidomide (CC-4047) monotherapy in subjects with refractory or relapsed and refractory multiple myeloma who discontinued from Treatment Arm B (dexamethasone alone) of Study CC-4047-MM-003 due to the development of documented disease progression during treatment. |
|
| E.2.2 | Secondary objectives of the trial |
| To evaluate the safety of pomalidomide monotherapy in subjects with refractory or relapsed and refractory multiple myeloma who discontinued treatment after being treated in the dexamethasone alone arm (Treatment Arm B) in Study CC-4047-MM-003 due to the development of documented disease progression during treatment. |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1.Subjects with refractory or relapsed and refractory multiple myeloma
who were enrolled in Study CC-4047-MM-003 and discontinued study
therapy with dexamethasone alone (Treatment Arm B) after at least
starting the second cycle of dexamethasone treatment and due to
development of documented disease progression according to the IMWG
criteria and as decided by an IRAC.
2.Must be ≥ 18 years at the time of signing the informed consent form.
3.The subject must understand and voluntarily sign an informed consent
document prior to any study related assessments/procedures being
conducted. The only exception is if a skeletal survey was performed
within 90 days prior to the start of Cycle 1, then a new survey will not be
required.
4.Must be able to adhere to the study visit schedule and other protocol
requirements.
5.Subjects must have documented diagnosis of multiple myeloma and
have measurable disease (serum M-protein ≥ 0.5g/dL or urine M-protein
≥ 200 mg/24 hours).
6.Eastern Cooperative Oncology Group (ECOG) performance status score
of 0, 1, or 2.
7. Females of childbearing potential (FCBP†) must agree to utilize two
reliable forms of contraception simultaneously or practice true
abstinence [when this is in line with the preferred and usual lifestyle of
the subject. Periodic abstinence (e.g., calendar, ovulation,
symptothermal, post ovulation methods) and withdrawal are not
acceptable methods of contraception]from heterosexual contact for at
least 28 days before starting study drug, while participating in the study
(including dose interruptions), and for at least 28 days after study
treatment discontinuation and must agree to regular pregnancy testing
during this timeframe.
8.Females must agree to abstain from breastfeeding during study
participation and 28 days after study discontinuation.
9. Males must agree to either use a latex condom during any sexual
contact with FCBP or practice true abstinence [when this is in line with
the preferred and usual lifestyle of the subject. Periodic abstinence (e.g.
calendar, ovulation, symptothermal, post-ovulation methods) and
withdrawal are not acceptable methods of contraception] while
participating in the study and for 28 days following discontinuation from
this study, even if he has undergone a successful vasectomy.
10.Males must also agree to refrain from donating semen or sperm while
on pomalidomide and for 28 days after discontinuation from this study
treatment.
11.All subjects must agree to refrain from donating blood while on study
drug and for 28 days after discontinuation from this study treatment.
12.All subjects must agree not to share study medication. |
|
| E.4 | Principal exclusion criteria |
1.Subjects with multiple myeloma who were not treated as a part of
Study CC-4047-MM-003 (Arm B).
2.Subjects who received anti-myeloma, or anti-cancer therapies within
the last 14 days of wash-out period before initiation of study treatment.
3.Subjects who discontinued CC-4047-MM-003 study ≥120 days.
4.Subjects who initiate another anti-myeloma therapy from the time of
disease progression on study CC-4047-MM-003 to the time of treatment
initiation in the companion study.
5.Any of the following laboratory abnormalities:
•Absolute neutrophil count (ANC) < 1,000/µL.
•Platelet count < 75,000/µL for subjects in whom < 50% of bone
marrow nucleated cells are plasma cells; or a platelet count < 30,000/µL
for subjects in whom ≥ 50% of bone marrow nucleated cells are plasma
cells
•Creatinine Clearance < 45 mL/min according to Cockcroft-Gault
formula (if creatinine clearance calculated from the 24-hour urine
sample is >=45 mL/min, patient will qualify for the trial)
•Corrected serum calcium > 14 mg/dL (> 3.5 mmol/L);
•Hemoglobin < 8 g/dL (< 4.9 mmol/L; prior RBC transfusion or
recombinant human erythropoietin use is permitted)
•Serum SGOT/AST or SGPT/ALT > 3.0 x upper limit of normal (ULN)
•Serum total bilirubin > 2.0 mg/dL (34.2 μmol/L); or > 3.0 x ULN for
subjects with hereditary benign hyperbilirubinaemia
6.Prior history of malignancies, other than MM, unless the subject has
been free of the disease for ≥ 5 years. Exceptions include the following:
•Basal or Squamous cell carcinoma of the skin
•Carcinoma in situ of the cervix or breast
•Incidental histologic finding of prostate cancer (TNM stage of T1a or
T1b)
7.Hypersensitivity to thalidomide or lenalidomide. (This includes ≥
Grade 3 rash during prior thalidomide or lenalidomide therapy).
8.Peripheral neuropathy ≥ Grade 2.
9.Subjects who received an allogeneic bone marrow or allogeneic
peripheral blood stem cell transplant less than 12 months prior to
initiation of study treatment and who have not discontinued
immunosuppressive treatment for at least 4 weeks prior to initiation of
study treatment and are currently dependent on such treatment.
10.Subjects who are planning for or who are eligible for stem cell
transplant.
11.Subjects with any one of the following:
•Congestive heart failure (NY Heart Association Class III or IV)
•Myocardial infarction within 12 months prior to starting study
treatment
•Unstable or poorly controlled angina pectoris, including Prinzmetal
variant angina pectoris
12.Subjects who received any of the following within the last 14 days of
initiation of study treatment:
•Plasmapheresis
•Major surgery (kyphoplasty is not considered major surgery)
•Radiation therapy
13.Use of any investigational agents within 28 days or 5 half lives
(whichever is longer) of treatment.
14.Subjects with chronic conditions such as rheumatoid arthritis,
multiple sclerosis and lupus, which likely need additional steroid or
immunosuppressive treatments in addition to the study treatment.
15.Any condition including the presence of laboratory abnormalities,
which places the subject at unacceptable risk if he/she were to
participate in the study.
16.Incidence of gastrointestinal disease that may significantly alter the
absorption of pomalidomide.
17.Subjects unable or unwilling to undergo antithrombotic prophylactic
treatment.
18.Any serious medical condition, laboratory abnormality, or psychiatric
illness that would prevent the subject from signing the informed consent
form.
19.Pregnant or breastfeeding females.
20.Known HIV positivity or active infectious hepatitis A, B or C. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| The primary endpoint is overall response rate (ORR) using the new International Myeloma Working Group Uniform (IMWG) response criteria. An analysis comparing the results of response assessments judged by the EMBT criteria (Blade, 1998) to those of the IMWG criteria will also be performed. |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
| E.5.2 | Secondary end point(s) |
• Safety (type, frequency, and severity of adverse events [AEs], and relationship of AEs to study drug)
• Progression-free survival (PFS)
• Time to progression (TTP)
• Duration of response
• Overall survival (OS)
|
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
|
| 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 | Yes |
| E.6.6 | Pharmacokinetic | No |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| 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) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | No |
| E.8.1.1 | Randomised | No |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | No |
| E.8.1.5 | Parallel group | No |
| 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) | No |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 1 |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 8 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 64 |
| 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 | No |
| 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 |
| Canada |
| Australia |
| Russian Federation |
| Switzerland |
|
| 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 | 5 |
| E.8.9.1 | In the Member State concerned months | 0 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 5 |
| E.8.9.2 | In all countries concerned by the trial months | 0 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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