E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Waldenström's Macroglobulinemia (WM) is an uncommon B-cell lymphoproliferative disorder that predominantly involves older patients with a slight male preponderance. WM resembles myeloma and chronic lymphocytic leukemia, but has been described as a low-grade lymphoplasmacytic lymphoma characterized by its over production of monoclonal immunoglobulin M (IgM). |
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MedDRA Classification |
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 |
The primary objective is to evaluate the efficacy of epratuzumab in WM as determined by the response rate for patients with partial or complete responses. |
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E.2.2 | Secondary objectives of the trial |
To evaluate the duration of response (DR) and time to progression (TTP). To examine the safety, tolerability and immunogenicity of epratuzumab as determined by adverse experiences/toxicity, changes in vital signs and criticial laboratory data and human anti-human antibodies (HAHA). To obtain pharmacokinetics determined from serum epratuzumab levels and pharmacodynamics determined from peripheral blood B-cell counts. |
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
1. Male or females, 18 years old or greater. 2. Documented diagnosis of WM satisfying criteria proposed at 2nd International Workshop on WM, Athens, Greece, 2002. 3. Measurable disease, defined as serum monoclonal IgM protein greater than or equal to 1000 mg/dL by electrophoresis. 4. Lymphoplasmacytic infiltration of the bone marrow > 10% involvement. 5. Failed at least one, but no more than 3, regimen(s) of prior therapy. 6. Karnofsky Performance Status (KPS) greater than or equal to 60. 7. Minimal life expectancy of 6 months. 8. Must be willing and able to give informed consent. |
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E.4 | Principal exclusion criteria |
1. Pregnant women. 2. Lactating women, unless they agree not to breastfeed for a period of 3 months after completing treatment. 3. Women of childbearing potential and fertile men who are unwilling to practice birth control during and for a period of 12 weeks after completing treatment. 4. Major surgery, radiation, chemotherapy, stem cell transplant, or any other therapy within 4 weeks prior to enrollment and recovered from all treatment-related toxicity. 5. Prior therapies must not include more than one prior therapy with rituximab, and patients who were refractory to rituximab are excluded, where refractory is defined as failure to achieve an objective response to rituximab or having progression of disease within 6 months after rituximab. 6. Prior therapy with other murine, chimeric, human or humanized monoclonal antibodies, unless HAHA is negative. 7. Prior treatment with any other investigational agents, unless follow-up is completed and patient is off study. 8. < 2 weeks beyond corticosteroids. 9. Hemoglobin < 7.0 g/dL, absolute neutrophil count, < 1000 mm³, platelets < 50,000/mm³, without ongoing transfusional support. 10. Serum creatinine > 1.5 X Institutional Upper Limit of Normal (IULN). 11. Serum bilirubin > 1.5 X ILUN, Alkaline phosphatase > 1.5 IULN, ALT (SGPT > 1.5 X IULN and/or AST (SGOT) > 1.5 X IULN. 12. Other primary malignancy (other than squamous or basal cell skin cancer, or cervical cancer in-situ) within 5 years. 13. Known HIV positive or active hepatitis B or C or presence of hepatitis B or C surface antigens. 14. Significant concurrent medical condition that could affect the patient's ability to tolerate or complete the study.
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E.5 End points |
E.5.1 | Primary end point(s) |
Toxicity will be graded according to the National Cancer Institute (NCI) Common Toxicity Criteria, version 3.0. Treatment responses will be categorized according to response criteria from 2nd International Workshop on WM. Treatment efficacy will be assessed by overall response rates (PR, CR) as well as duration of response and time-to-progression; safety, from adverse events, toxicity, and changes in vital signs or laboratory values; pharmacokinetics, from IMMU-103 levels; pharmacodynamics, from B-cell levels; and immunogenicity, from HAHA titers. |
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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 | Yes |
E.6.7 | Pharmacodynamic | Yes |
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) | 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 | 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 | 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 | 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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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 | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 5 |