E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
The occurrence of renal failure is an emergency situation in patients with multiple myeloma. A fast active relatively, non-toxic protocol seems presently the best option for attempts to reverse renal insufficiency. Therefore we have designed a small Phase 2 trial with a Bortezomib containing regimen, which intends to revert renal failure in a greater proportion of patients compared to conventional regimens. |
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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 |
The primary objectives of the study are to evaluate the activity of Bortezomib – Doxorubicin - Dexamethasone in subjects with acute renal failure as measured by reversal of acute renal failure
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E.2.2 | Secondary objectives of the trial |
The secondary objectives of this study are to evaluate: - tumor response (complete and partial response), - the safety of Bortezomib – Doxorubicin – Dexamethasone in this patient population, - the activity Bortezomib – Doxorubicin – Dexamethasone on progression free survival, - the activity Bortezomib – Doxorubicin – Dexamethasone on overall survival.
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
- Histologically confirmed diagnosis of multiple myeloma with evaluable disease parameters - Acute renal failure in patients with multiple myeloma - by newly diagnosed patients: glomerular filtration rate (< 50ml/min). Diagnosis of paraprotein induced renal failure must be established (by clinical and laboratory findings including kidney biopsy-if indicated); - by previously treated patients (without limitation by number of treatment lines): decrease in GFR > 25% compared to pre renal failure level (within 4 weeks), or to <50ml / min, concomitantly with either increase in paraproteins (>25%) and/or decrease in hemoglobin ≥ 2 g/dl (within 4 weeks) and/or increase in bone marrow plasma infiltration as signs of disease progression; - Age > 20 years - ECOG performance status of ≤ 3 (Appendix IV) - Platelet count > 50.000/µl - WBC > 2000/µl - Neutrophils ³ 1000/µl - Total bilirubin < 1.5 x upper limit of normal, AST, ALT < 2.5 x upper limit of normal - Fertile women and men of childbearing potential (<2 years after last menstruation in women) must use effective means of contraception (oral contraceptives, intrauterine contraceptive device, barrier method of contraception in conjunction with spermicidal jelly or surgically sterile); - Negative serum or urine β-HCG pregnancy test at screening for subjects of child-bearing potential - Patient’s written informed consent
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E.4 | Principal exclusion criteria |
- History of malignancy other than squamous cell carcinoma, basal cell carcinoma of the skin or carcinoma in situ of the cervix within the last 3 years - Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to study treatment start, or anticipation of the need for major surgical procedure during the course of the study. - Evidence of CNS involvement or spinal cord compression. - Neuropathy ≥ Grade 2 - A history of uncontrolled seizures, central nervous system disorders or psychiatric disability judged by the investigator to be clinically significant and adversely affecting compliance to study drug. - NYHA Status > 2, i.e. clinically significant cardiac disease, (congestive heart failure, symptomatic coronary artery disease, cardiac arrhythmias, and arterial hypertension not well controlled with medication) or myocardial infarction within the last 6 months (see also Appendix VIII). - Evidence of bleeding diathesis or coagulopathy - Serious, non-healing wound or ulcer - Evidence of any severe active acute or chronic infection. - Evidence of other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates use of an investigational drug or patient at high risk from treatment complications - Patient is known to be HIV-positive, Hbs-antigen positive or HCV-RNA-positive - Pregnant women or nursing mothers - Have received bortezomib within 4 weeks before the planned start of treatment - Half body irradiation < 28 days before enrollment - Has known or suspected hypersensitivity or intolerance to boron, mannitol, or heparin, if an indwelling catheter is used
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E.5 End points |
E.5.1 | Primary end point(s) |
Reversal of renal failure (increase of the GFR level > 50 % to pre-treatment GFR level or equal to the last “normal” pre-study GFR level). |
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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 | Information not present in EudraCT |
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) | Information not present in EudraCT |
E.7.4 | Therapeutic use (Phase IV) | Information not present in EudraCT |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
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) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
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.8.5 | The trial involves multiple Member States | Yes |
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 |
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E.8.7 | Trial has a data monitoring committee | Information not present in EudraCT |
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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Circumstances that may warrant termination include, but are not limited to: - Determination of unexpected, significant, or unacceptable risk to patients - Failure to enter patients at an acceptable rate - Insufficient adherence to protocol requirements - Insufficient complete and/or evaluable data - Plans to modify, suspend or discontinue the development of the study drug
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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 | 3 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 6 |