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 | 8.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10008976 |
E.1.2 | Term | Chronic lymphocytic leukemia |
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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 objective of this study is to determine best disease response to treatment with CAMPATH administered subcutaneously (SC) for up to 18 weeks in patients with B-Cell Chronic Lymphocytic Leukemia (B CLL) who have been previously treated. |
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E.2.2 | Secondary objectives of the trial |
Secondary objectives are to determine the •Progression free survival (PFS) •Duration of response •Overall survival •Minimal residual disease (MRD) status by flow cytometry analysis of bone marrow and peripheral blood •And to evaluate the safety of CAMPATH administered SC
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
(1) A diagnosis of B-CLL; according to the NCIWG Criteria (Appendix D) (2) At least 18 years old (3) World Health Organization (WHO) performance status of 0, 1, or 2 (4) Life expectancy ≥12 weeks (5) Previous therapy with at least one but no more than five regimens (single agent or combination regimen). One regimen is defined as consecutive, contiguous cycles of the same drug(s) with no treatment interruptions lasting >3 months. (6) Patient requires treatment for chronic lymphocytic leukemia (CLL) per the following criteria * Rai stage III or IV (Appendix D). * Rai stage 0-II with at least one of the following: - Evidence of progressive marrow failure as manifested by the development of, or worsening of, anemia and/or thrombocytopenia - Massive (i.e., >6 cm below the left costal margin) or progressive splenomegaly - Progressive lymphocytosis with an increase of >50% over a 2 month period or an anticipated doubling time of <6 months - Lymphocyte count >100 ×109/L - B symptoms (7) More than 3 weeks since prior chemotherapy. Patient must have recovered from the acute side effects incurred as a result of previous therapy. (8) More than 3 weeks since using investigational agents. Patient must have recovered from the acute side effects incurred as a result of previous therapy. (9) Serum creatinine and conjugated (direct) bilirubin ≤2 x the institutional upper limit of normal (ULN) unless secondary to direct infiltration of the liver with CLL. (10) Female patients with childbearing potential must have a negative pregnancy test (serum or urine) within 2 weeks of first dose of study drug(s). All patients must agree to use an effective contraceptive method while on study treatment, if appropriate, and for a minimum of 6 months following study therapy. (11) Signed, written informed consent
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E.4 | Principal exclusion criteria |
(1) Positive Coombs test and evidence of active hemolysis (2) Platelet count <50 ×109/L without splenomegaly (3) History of anaphylaxis following exposure to rat or mouse derived CDR grafted humanized monoclonal antibodies (4) Previously treated with CAMPATH (5) Previous bone marrow transplant (6) Known central nervous system (CNS) involvement with B-CLL (7) Active infection, including human immunodeficiency virus (HIV) positive (8) Active secondary malignancy (9) Recent documented history (within 2 years) of active tuberculosis (TB), current active TB infection, currently receiving anti-tuberculous medication (e.g., isoniazid, rifampin, streptomycin, pyrazinamide, or others) (10) Active hepatitis or a history of prior viral hepatitis B or hepatitis C, or positive hepatitis B serologies. Patients with a positive hepatitis B surface antibody (HBsAb) test with a documented history of prior hepatitis B immunization are eligible as long as other criteria are met (ie, negative tests for: hepatitis B surface antigen [HBsAg], hepatitis B core antibody [HBcAb] and hepatitis C virus antibody [HCVAb]). (11) Other severe, concurrent diseases (e.g., cardiac or pulmonary disease), mental disorders, or major organ malfunction (liver, kidney) that could interfere with the patient’s ability to participate in the study (12) Pregnant or nursing women (13) Cytomegalovirus (CMV) positive by polymerase chain reaction (PCR) (above the level of detection). A patient that is PCR positive will require treatment to reduce the viral load to a non-detectable level, but such a patient may be reconsidered for study entry once the infection has been treated (see Section 6.1.1). (14) Medical condition requiring chronic use of oral corticosteroids at a dose higher than physiologic replacement.
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy endpoint is the best overall response rate for up to 18 weeks of CAMPATH administered SC using the National Cancer Institute Working Group (NCIWG) criteria for determining response. Overall response rate = Number of CR (complete repons) + PR (partial respons) patients / numbers of patients in full analysis set |
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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 | Yes |
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 | Information not present in EudraCT |
E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
E.7.1.3 | Other | Information not present in EudraCT |
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 | Yes |
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 | Yes |
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 | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 14 |
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 | 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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Trial will stop when 60% of enrolled patients have expired or 4 years after the last patient was enrolled, whichever occurs earlier.
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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 | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 6 |