E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Newly diagnosed Waldenstrom's macroglobulinemia (WM) |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 8.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10054695 |
E.1.2 | Term | Waldenstrom's macroglobulinemia |
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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 determine the response rate [the combined complete response (CR) + partial response (PR) + minimal response (MR)] following treatment with Bortezomib, Dexamethazone and Rituximab in patients with previously untreated Waldenstrom's Macroglobulinemia. |
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E.2.2 | Secondary objectives of the trial |
• To determine time to progression following treatment with BDR • To assess the safety and tolerability of Bortezomib, Dexamethazone and Rituximab in patients with Waldenstrom's Macroglobulinemia.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Clinicopathological diagnosis of Waldenstrom’s macroglobulinemia as defined by consensus panel one of the Second International Workshop on Waldenstrom’s macroglobulinemia.1 All patients with the diagnosis of WM will be evaluable for response according to the response criteria (section 8.1) • No prior systemic treatment for WM. Prior plasmapheresis to control hyperviscosity, is allowed. In that case baseline monoclonal protein levels for assessment of response will be the levels prior to plasmapheresis, if this is the higher value prior to treatment initiation • Patients must have at least one of the following indications to initiate treatment as defined by “Consensus Panel Two” recommendations from the Second International Workshop on Waldenstrom’s Macroglobulinemia41. 1. Recurrent fever, night sweats, weight loss, fatigue 2. Hyperviscosity 3. Lympadenopathy which is either symptomatic or bulky (≥5cm in maximum diameter) 4. Symptomatic hepatomegaly and/or splenomegaly 5. Symptomatic organomegaly and/or organ or tissue infiltration 6. Peripheral neuropathy due to WM 7. Symptomatic cryoglobulinemia 8. Cold agglutinin anemia 9. Immune hemolytic anemia and/or thrombocytopenia 10. Nephropathy related to WM 11. Amyloidosis related to WM 12. Hemoglobin ≤10g/dL 13. Platelet count <100x109/L 14. Serum monoclonal protein >5g/dL even with no symptoms • CD20 positive disease based on any previous bone marrow immunohistochemistry or flow cytometric analysis performed up to 3 months prior to enrollment. • Karnofsky performance status 60. • Life-expectancy >3 months. • Baseline platelet count 50109/L, and absolute neutrophil count 0.75109/L. • Meet the following pretreatment laboratory criteria at the Screening visit conducted within 28 days of study enrollment: • AST (SGOT): 3 times the upper limit of institutional laboratory normal. • ALT (SGPT): 3 times the upper limit of institutional laboratory normal. • Total Bilirubin: 2 times the upper limit of institutional laboratory normal, unless clearly related to the disease. • Calculated or measured creatinine clearance: 30 mL/minute. • Serum sodium >130 mmol/L.
• Voluntary written informed consent before performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care.
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E.4 | Principal exclusion criteria |
• Prior systemic treatment with WM (plasmapheresis is allowed) • Myocardial infarction within 6 months prior to enrollment or has New York Hospital Association (NYHA) Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities. Prior to study entry, any ECG abnormality at Screening has to be documented by the investigator as not medically relevant. • Patient has hypersensitivity to dexamethasone, bortezomib, boron or mannitol. • Serious medical or psychiatric illness likely to interfere with participation in this clinical study. • Cardiac amyloidosis • Peripheral neuropathy or neuropathic pain grade 2 or higher as defined by NCI CTCAE version 3 • Women who are pregnant. Women who are breast-feeding and do not consent to discontinue breast-feeding. Women of childbearing age who are not willing to use effective anti-conceptive methods for the duration of the study and 6 months thereafter. Men who do not consent not to father a child during the treatment period and six months thereafter.
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E.5 End points |
E.5.1 | Primary end point(s) |
• To determine the response rate [the combined complete response (CR) + partial response (PR) + minimal response (MR)] following treatment with BDR in patients with previously untreated WM. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | Information not present in EudraCT |
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 | 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 | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 19 |
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 | Information not present in EudraCT |
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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End of trial in a Member State End of trial in a Member State of the European Union is defined as the time at which it is deemed that sufficient patients have been recruited and completed the trial as stated in the regulatory application, in the Member State. Poor recruitment (recruiting less than anticipated number) by a Member State is not a reason for premature termination.
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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 | 8 |
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 | 8 |
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 |