| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Relapsed and refractory multiple myeloma |
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| E.1.1.1 | Medical condition in easily understood language |
| Malignant disease of plasma cells (Multiple Myeloma) in advance state |
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| E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
| MedDRA Classification |
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
To investigate the best objective response
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| E.2.2 | Secondary objectives of the trial |
To determine progression free survival of Pomalidomide in combination with low-dose Dexamethasone and intravenous Cyclophosphamide in case of suboptimal response or first evidence of progressive disease in subjects with relapsed or refractory MM
To evaluate safety: incidence of Second Primary Malignancies (SPM) (according to CTCAE 4.0: hematological toxicity, sensoric neuropathy, infections > CTC III)
To evaluate overall survival
To assess time to subsequent therapy
To assess time to myeloma response
To assess cytogenetic profile |
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| 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.
2. Understand and voluntarily sign an informed consent prior to any study related assessments/procedures are 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). In case of oligosecretory myeloma: involved FLC level ≥ 10 mg/dl, provided sFLC ratio is abnormal.
5. Subjects must have had at least two prior anti-myeloma regimens (incl. bortezomib and lenalidomide) and must have been progressed under the last prior treatment. Induction therapy followed by ASCT and consolidation/ maintenance will be considered as one regimen.
6. ECOG performance status score of 0, 1, or 2.
7. Females of childbearing potential (FCBP1) must agree:
Females of childbearing potential with regular or no menstrual cycles must agree to have pregnancy tests weekly for the first 28 days of study participation and then every 28 days while taking pomalidomide, at study discontinuation, and at Day 28 following the last dose of pomalidomide. Females of childbearing potential with irregular menstrual cycles must agree to have pregnancy tests weekly for the first 28 days of study participation and then every 14 days while taking pomalidomide, at study discontinuation, and at Days 14 and 28 following the last dose of pomalidomide.
to use two reliable forms of contraception simultaneously or to practice complete abstinence (True abstinence is acceptable when this is in line with the preferred and usual lifestyle of the subject. Periodic abstinence [eg calendar, ovulation, symptothermal or post-ovulation methods] and withdrawal are not acceptable methods of contraception.) from heterosexual contact during the following time periods related to this study: 1) for at least 28 days before starting pomalidomide; 2) while taking pomalidomide; 3) during dose interruptions; and 4) for at least 28 days after the last dose of pomalidomide.
to abstain from breastfeeding during study participation and 28 days after study drug discontinuation.
8. Males must agree:
to practice complete abstinence (True abstinence is acceptable when this is in line with the preferred and usual lifestyle of the subject. Periodic abstinence [eg calendar, ovulation, symptothermal or post-ovulation methods] and withdrawal are not acceptable methods of contraception.) or agree to use a condom during sexual contact with a pregnant female or a FCBP while taking pomalidomide, during dose interruptions and for at least 28 days after the last dose of pomalidomide, even if he has undergone a successful vasectomy.
to refrain from donating semen or sperm while on Pomalidomide and for 28 days after discontinuation from this study treatment.
9. All subjects must agree to refrain from donating blood while on study drug and for 28 days after discontinuation from this study treatment.
10. All subjects must agree not to share medication.
1 A Female of childbearing Potential is a female who: 1) has achieved menarche at some point, 2) has not undergone a hysterectomy or bilateral oophorectomy or 3) has not been naturally postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 24 consecutive months (ie, has had menses at any time in the preceding 24 consecutive months).
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| E.4 | Principal exclusion criteria |
TThe presence of any of the following will exclude a subject from enrolment:
1. Any of the following laboratory abnormalities:
Absolute neutrophil count (ANC) < 1,000/μL.
Subject with platelet count 30,000/µL are not eligible regardless of the percentage of plasma cells in the bone marrow. For subject with platelet count > 30,000/µL and < 75,000/µL, percentage of plasma cells in bone marrow should be 50%.
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) except due to multiple myeloma.
Serum total bilirubin > 2.0 mg/dL (34.2 μmol/L); or > 3.0 x ULN for subjects with hereditary benign hyperbilirubinemia.
GFR < 30 ml/min or patient requiring hemodialysis
2. 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 histological finding of prostate cancer (TNM stage of T1a or T1b).
3. Previous therapy with Pomalidomide.
4. Hypersensitivity to Thalidomide, Lenalidomide, Cyclophosphamide and its metabolites or Dexamethasone (this includes ≥ Grade 3 rash during prior Thalidomide or Lenalidomide therapy).
5. Peripheral neuropathy ≥ Grade 2.
6. 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.
7. Subjects who are planning for or who are eligible for stem cell transplant.
8. 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.
9. Subjects who received any of the following within the last 14 days of initiation of study treatment:
Major surgery (kyphoplasty is not considered major surgery)
Use of any anti-myeloma drug therapy.
10. Use of any investigational agents within 28 days or five half-lives (whichever is longer) of treatment.
11. Incidence of gastrointestinal disease that may significantly alter the absorption of Pomalidomide.
12. Subjects unable or unwilling to undergo antithrombotic prophylactic treatment.
13. Any active, uncontrolled infection.
14. Cystitis.
15. Disturbance of urinary flow (e.g. Urolithiasis).
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.
19. Any condition that confounds the ability to interpret data from the study
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| E.5 End points |
| E.5.1 | Primary end point(s) |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| Evaluation of response at each end of the cycle |
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| E.5.2 | Secondary end point(s) |
To determine progression free survival of Pomalidomide in combination with low-dose Dexamethasone and intravenous Cyclophosphamide in case of suboptimal response or first evidence of progressive disease in subjects with relapsed or refractory MM
To evaluate safety: incidence of Second Primary Malignancies (SPM) (according to CTCAE 4.0: hematological toxicity, sensoric neuropathy, infections > CTC III)
To evaluate overall survival
To assess time to subsequent therapy
To assess time to myeloma response
To assess cytogenetic profile
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|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
To determine progression free survival of Pomalidomide in combination with low-dose Dexamethasone and intravenous Cyclophosphamide in case of suboptimal response or first evidence of progressive disease in subjects with relapsed or refractory MM - Timepoint of evaluation at the end of each cycle
To evaluate safety: incidence of Second Primary Malignancies (SPM) (according to CTCAE 4.0: hematological toxicity, sensoric neuropathy, infections > CTC III) - Timepoint of evaluation at the end of each cycle
To evaluate overall survival - Timepoint of evaluation at the end of each cycle and at each follow-up visit
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| 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 | Yes |
| 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) | 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 | No |
| E.8.1.2 | Open | Yes |
| 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 | 7 |
| E.8.5 | The trial involves multiple Member States | No |
| 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
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| 2 years after enrollment of the last patient. Imnovid is per se a continous treatment. If a patient is still responding to the IMP after 2 years of application treatment is continued. According to the primary objective, best response in the 2 year application frame is documented. |
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| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 2 |
| E.8.9.1 | In the Member State concerned months | 0 |
| E.8.9.1 | In the Member State concerned days | 0 |
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