E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
B-cell Chronic Lymphocytic Leukemia |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 7.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10008959 |
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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 evaluate the efficacy of HuMax-CD20 in patients with B-cell Chronic Lymphocytic Leukemia (B-CLL) who have failed fludarabine and alemtuzumab |
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E.2.2 | Secondary objectives of the trial |
To determine the host immune response to HuMax-CD20 To determine the pharmacokinetic profile of HuMax-CD20 To determine the safety of HuMax-CD20 |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1) Tumor cell phenotype consistent with B-CLL: • CD5 • CD20 • CD23 2) Patients with active B-CLL and with an indication for treatment, defined as presenting one of the following conditions as defined by the NCIWG guidelines (1): a. evidence of progressive marrow failure as manifested by development of, or worsening of anemia or thrombocytopenia; or, b. massive (≥ 6 cm below the left costal margin) or progressive splenomegaly; or, c. massive nodal clusters (≥ 10 cm in longest diameter) or progressive lymphadenopathy; or, d. progressive lymphocytosis with an increase of > 50% over a two month period or an anticipated doubling time < 6 months; or, e. any one of the following disease related conditions: i. 10% or greater weight loss within the previous six months, or ii. fevers ≥ 100.5°F (38.0°C) for ≥ 2 weeks without evidence of infection, or iii. night sweats without evidence of infection.
3) Failing at least one fludarabine-containing treatment regimen (a minimal of at least 2 cycles), defined as: a. Refractory to one fludarabine-containing treatment regimen, defined as: i. failure to achieve at least PR to at least one fludarabine-containing treatment regimen; or, ii. disease progression while on a fludarabine-containing treatment regimen; or, iii. disease progression in responders within 6 months of the last dose of a fludarabine-containing treatment regimen
4) Failing at least one alemtuzumab-containing treatment regimen (a minimal of at least 12 administrations), defined as: a. Refractory to one alemtuzumab-containing treatment regimen, defined as: i. failure to achieve at least PR to at least one alemtuzumab-containing treatment regimen; or, ii. disease progression while on a alemtuzumab-containing treatment regimen; or, iii. disease progression in responders within 6 months of the last dose of a alemtuzumab-containing treatment regimen
b. Considered inappropriate for treatment with alemtuzumab due to lymphadenopathy with at least one lymph node > 5 cm and requiring therapy
5) ECOG Performance Status of 0, 1 or 2 6) Life expectancy of at least 6 months 7) Age ≥ 18 years 8) Following receipt of verbal and written information about the study, the patient must provide signed informed consent before any study related activity is carried out
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E.4 | Principal exclusion criteria |
1) Previous treatment with alemtuzumab within 6 weeks prior to Visit 2 2) Previous autologous stem cell transplantation within 6 months prior to Visit 2 3) Allogeneic stem cell transplantation 4) Radioimmunotherapy 5) Received any of the following treatments within 4 weeks prior to Visit 2: • Anti-cancer therapy (e.g. alkylating agents, anti-metabolites, purine analogues, monoclonal antibodies) • Glucocorticoid unless given in doses equivalent to ≤ 10 mg of prednisolone /day • Leukapheresis
6) Patients previously treated with HuMax-CD20 7) Known transformation to more aggressive B-cell malignancies (e.g. large B-cell Lymphoma, Richter’s Syndrome, or PLL). 8) Known CNS involvement of B-CLL 9) Past or current malignancy, except for: • Cervical carcinoma Stage 1B or less • Non-invasive basal cell and squamous cell skin carcinoma • Malignant melanoma with a complete response of a duration of > 10 years • Other cancer diagnoses with a complete response of a duration of > 5 years 10) Chronic or ongoing active infectious disease requiring systemic treatment such as, but not limited to, chronic renal infection, chronic chest infection with bronchiectasis, tuberculosis and active hepatitis C 11) Clinically significant cardiac disease including unstable angina, acute myocardial infarction within six months from Visit 1, congestive heart failure, and arrhythmia requiring therapy, with the exception of extra systoles or minor conduction abnormalities 12) Significant concurrent, uncontrolled medical condition including, but not limited to, renal, hepatic, hematological, gastrointestinal, endocrine, pulmonary, neurological, cerebral or psychiatric disease 13) History of significant cerebrovascular disease 14) Known HIV positive 15) Positive serology for hepatitis B, defined as a positive test for HBsAg and/or a combination of a positive test for anti-HBs and anti-HBc 16) Removed by Amendment 2 17) Known or suspected hypersensitivity to components of investigational product 18) Patients with pleural effusion or ascites of significant degree, defined as detectable by physical examination 19) ECOG Performance Status of 3 or 4 20) Life expectancy less than 6 months 21) Patients who have received treatment with any non-marketed drug substance or experimental therapy within 4 weeks prior to Visit 2 22) Current participation in any other interventional clinical study 23) Patients known or suspected of not being able to comply with a study protocol (e.g. due to alcoholism, drug dependency or psychological disorder) 24) Breast feeding women or women with a positive pregnancy test at Visit 1 25) Women of childbearing potential not willing to use adequate contraception during study and one year after last dose of HuMax-CD20. Adequate contraception is defined as hormonal birth control or intrauterine device. For patients in the USA the use of a double barrier method is also considered adequate.
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E.5 End points |
E.5.1 | Primary end point(s) |
Objective response as measured over a 24 week period from start of treatment assessed by an Independent endpoints Review Committee (IRC), according to the NCIWG guidelines. |
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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 | 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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
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.8.3 |
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 | 60 |
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 | Yes |
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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Last visit of last patient |
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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 | 6 |
E.8.9.1 | In the Member State concerned months | 3 |
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 | 3 |
E.8.9.2 | In all countries concerned by the trial days | 0 |