| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Relapsed or refractory multiple myeloma (MM) in patients with moderate or severely impaired renal function. |
|
| E.1.1.1 | Medical condition in easily understood language |
| (Blood cancer) certain blood cells multiply abnormally in the bone marrow, impair the production of other blood cells and produce proteins that cumulate in other organs impairing their functioning. |
|
| 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 | 21.0 |
| 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 |
| Evaluate efficacy of the combination of pomalidomide and low-dose dexamethasone in subjects with RRMM and impaired renal function. |
|
| E.2.2 | Secondary objectives of the trial |
- Evaluate renal efficacy of the combination of pomalidomide and low-dose
dexamethasone in subjects with various degrees of renal impairment.
- Evaluate safety and tolerability of the combination of pomalidomide and low-dose dexamethasone in subjects with RRMM and impaired renal function.
- Evaluate the pharmacokinetics of pomalidomide in subjects with various degrees of renal impairment. |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
Subjects must satisfy the following criteria to be enrolled in the study.
1. Must be ≥ 18 years at the time of signing the informed consent form.
2. Understand and voluntarily sign an informed consent document prior to any study related assessments/procedures being conducted.
3. Able to adhere to the study visit schedule and other protocol requirements.
4. Subjects must have documented diagnosis of multiple myeloma and have measurable disease (serum M-protein ≥ 0.5 g/dL or urine M-protein ≥ 200 mg/24 hours).
5. Subjects must have had at least 1 prior antimyeloma regimen including lenalidomide and documented progression as per the IMWG uniform response criteria (Durie, 2006) during or after the last antimyeloma regimen. Induction therapy followed by ASCT and consolidation/ maintenance will be considered as one regimen.
6. Subjects must have an impaired renal function with an estimated GFR of
< 45 mL/min/1.73 m2 according to the MDRD equation.
a. Impaired renal function must be due to multiple myeloma which needs to be
confirmed by kidney biopsy.
b. Subjects may have acute myeloma related renal failure or chronic myeloma related renal failure; they may also have been treated with dialysis before, including dialysis with high cut off membranes.
7. ECOG performance status score of 0, 1, or 2
8. Females of childbearing potential must:
a. Have two negative pregnancy tests as verified by the study doctor prior to starting study therapy. She must agree to ongoing pregnancy testing during the course of the study, and after end of study therapy. This applies even if the subject practices true abstinence from heterosexual contact.
b. Either commit to true abstinence from heterosexual contact (which must be reviewed on a monthly basis) or agree to use, and be able to comply with, effective contraception without interruption, 28 days prior to starting IP, during the study therapy (including dose interruptions), and for 28 days after discontinuation of study therapy.
9. Male subjects must:
a. Must practice true abstinence or agree to use a condom during sexual contact with a pregnant female or a female of childbearing potential while participating in the study, during dose interruptions and for at least 28 days following IP discontinuation, even if he has undergone a successful vasectomy. |
|
| E.4 | Principal exclusion criteria |
The presence of any of the following will exclude a subject from enrollment:
1. Any significant medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from participating in the study.
2. Any condition including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study.
3. Renal insufficiency due to other reasons than multiple myeloma or due to hypercalcaemia only.
4. Any of the following laboratory abnormalities:
a. Absolute neutrophil count (ANC) < 1,000/μL
b. Subject with platelet count < 50,000/μL are not eligible regardless of the percentage of plasma cells in the bone marrow
c. Corrected serum calcium > 14 mg/dL (> 3.5 mmol/L)
d. Hemoglobin < 8 g/dL (< 4.9 mmol/L; prior RBC transfusion or recombinant human erythropoietin use is permitted)
e. Serum SGOT/AST or SGPT/ALT > 3.0 x upper limit of normal (ULN)
f. Serum total bilirubin > 2.0 mg/dL (34.2 μmol/L); or > 3.0 x ULN for subjects with hereditary benign hyperbilirubinemia
5. Prior history of malignancies, other than MM, unless the subject has been free of the disease for ≥ 5 years; exceptions include the following:
a. Basal or squamous cell carcinoma of the skin
b. Carcinoma in situ of the cervix or breast
c. Incidental histological finding of prostate cancer (TNM stage of T1a or T1b)
6. Previous therapy with pomalidomide.
7. Hypersensitivity to thalidomide, lenalidomide, or dexamethasone (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:
a. Congestive heart failure (NY Heart Association Class III or IV)
b. Myocardial infarction within 12 months prior to starting study treatment
c. 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:
a. Major surgery (kyphoplasty is not considered major surgery)
b. Use of any antimyeloma drug therapy
13. Use of any investigational agents within 28 days or five half-lives (whichever is longer) of treatment.
14. Incidence of gastrointestinal disease that may significantly alter the absorption of pomalidomide.
15. Subjects unable or unwilling to undergo antithrombotic prophylactic treatment.
16. Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subjects from signing the informed consent form.
17. Pregnant or breastfeeding females.
18. Known human immunodeficiency virus (HIV) positivity, active infectious hepatitis A, B, or C or chronic hepatitis B or C, as well as any systemic infection without specific antimicrobial treatment.
19. Any condition that confounds the ability to interpret data from the study. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| Overall response rate (ORR) according to the International Myeloma Working Group (IMWG) criteria |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| At Day 1 of each Cycle starting at Cycle 2 |
|
| E.5.2 | Secondary end point(s) |
1) Assessment of renal response.
2) Time to Myeloma response, time to renal response, duration of response (DOR), progression-free survival (PFS), time to progression (TTP), overall survival (OS).
3) Adverse events (AEs) assessment (type, frequency, seriousness, severity, relationship to pomalidomide and/or dexamethasone and outcomes) including second primary malignancy (SPM).
4) Pharmacokinetics (PK) of pomalidomide in subjects with RRMM and impaired renal function (moderate to severe renal impairment). |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
a) Assessment of renal response, Time to myeloma response, Time to renal response, PFS and TTP will be assesssed at Day 1 of each Cycle starting at Cycle 2
b) Duration of response - depending on when a response occurs
c) OS – continuously during the trial as well as during FU
d) AEs – continuously during the trial as well as during FU
e) PK – Please see page 34 of the protocol |
|
| 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 | Yes |
| 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) | 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 | No |
| E.8.1.1 | Randomised | Information not present in EudraCT |
| E.8.1.2 | Open | Information not present in EudraCT |
| E.8.1.3 | Single blind | Information not present in EudraCT |
| E.8.1.4 | Double blind | Information not present in EudraCT |
| E.8.1.5 | Parallel group | Information not present in EudraCT |
| E.8.1.6 | Cross over | Information not present in EudraCT |
| E.8.1.7 | Other | Information not present in EudraCT |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
| E.8.2.2 | Placebo | Information not present in EudraCT |
| E.8.2.3 | Other | Information not present in EudraCT |
| 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 | 2 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 20 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | No |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.7 | Trial has a data monitoring committee | No |
| 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
|
| 5 years after the enrollment of the last subject or longer if clinically indicated. |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 6 |
| E.8.9.1 | In the Member State concerned months | 6 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 6 |
| E.8.9.2 | In all countries concerned by the trial months | 6 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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