E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
patients with previously untreated CLL |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | SOC |
E.1.2 | Classification code | 10005329 |
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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 |
To assess the rate of complete and overall response using pentostatin, cyclophosphamide, and ofatumumab in patients with previously untreated CLL requiring therapy and to determine the proportion of patients who achieve a minimal residual disease (MRD) negative state as assessed by flow cytometry. |
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E.2.2 | Secondary objectives of the trial |
• To monitor and assess toxicity of pentostatin, cyclophosphamide, and ofatumumab in patients with previously untreated CLL. • To determine the progression-free survival in CLL patients treated with pentostatin, cyclophosphamide, and ofatumumab. • To assess the complete and overall response as well as progression free survival of CLL patients treated with pentostatin, cyclophosphamide, and ofatumumab • To determine if molecular prognostic parameters (ZAP-70, CD38, cytogenetic abnormalities identified by FISH, IgVH mutation status, etc) relate to response to PCO therapy. |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
FARMACOCINETICA/FARMACODINAMICA: Versione:1 Data:2010/07/21 Titolo:Pharmacokinetic study of Ofatumumab in a Single-Arm Multi-Center Trial of Pentostatin plus Cyclophosphamide with Ofatumumab (PCO) in Older Patients With Previously Untreated Chronic Lymphocytic Leukemia Obiettivi:-develop a sensitive, rapid, accurate, precise enzyme-linked immunoadsorbent assay (ELISA) validated in the Laboratory of Pharmacokinetics of Department of Pharmacology of Policlinico San Matteo, Pavia (Italy). -evaluate Ofatumumab concentration-time data using a statistical pharmacokinetics population program (P-Pharm).
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E.3 | Principal inclusion criteria |
Diagnosis of B-CLL defined by: Circulating lymphocytes of more than or equal to 5_109/L B lymphocytes (5000/_L) in the peripheral blood for the duration of at least 3 months. Flow cytometry confirmation of immunophenotype: CD5, CD19, CD20, CD23, CD79b, and surface Ig Active disease and indication for treatment based on modified NCI-WG guidelines [Hallek et al. 2008] defined by presenting at least any one of the following conditions: Evidence of progressive marrow failure as manifested by development of, or worsening of anemia and/or thrombocytopenia Massive (i.e. > 6 cm below the left costal margin) or progressive or symptomatic splenomegaly Massive nodes (i.e. > 10 cm in longest diameter) or progressive or symptomatic lymphadenopathy Progressive lymphocytosis with an increase of > 50% over a two month period or an lymphocyte doubling time < 6 months A minimum of any one of the following disease-related symptoms must be present: a) Unintentional Weight loss � 10% within the previous six months b) Fevers > 38.0 �C for N 2 weeks without evidence of infection c) Night sweats for more than 1 month without evidence of infection Not been previously treated for B-CLL (prior autoimmune hemolytic anemia treatment permitted) ECOG Performance Status of 0-2 Age N 65 years Signed written informed consent prior to performing any studyspecific procedures |
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E.4 | Principal exclusion criteria |
Prior therapy for B-CLL with any agent except corticosteroids used to treat autoimmune hemolytic anemia • Active autoimmune hemolytic anemia (AIHA) requiring corticosteroid therapy > 100 mg equivalent to hydrocortisone, or chemotherapy PCO Protocol Final Version, 17 August 2010 8 of 65 : • Known Richter transformation • Known CNS involvement of B-CLL • Any radiation therapy R 4 weeks prior to registration; • Any major surgery R 4 weeks prior to registration; • Chronic or current infectious disease requiring systemic antibiotics, antifungal, or antiviral treatment such as, but not limited to, chronic renal infection, chronic chest infection with bronchiectasis, tuberculosis and active Hepatitis C • Past or current malignancy with the exception of basal cell carcinoma of the skin or in situ carcinoma of the cervix or the breast unless the tumor was successfully treated with curative intend at least 2 years prior to trial entry. • Clinically significant cardiac disease including unstable angina, acute myocardial infarction within 6 months prior to Visit 1, congestive heart failure, and arrhythmia requiring therapy, with the exception of extra systoles or minor conduction abnormalities • History of significant cerebrovascular disease • Glucocorticoid unless given in doses R 100 mg/day hydrocortisone (or equivalent dose of other glucocorticoid) if for exacerbations other than B-CLL (e.g. asthma) • Known HIV positive • Positive serology for Hepatitis B (HB), defined as a positive test for HBsAg. In addition if negative for HBsAg but HBcAb positive and HBsAb negative a HB DNA test will be performed and if positive the subject will be excluded. Note: if HBcAb positive and HBsAb positive, which is indicative of a past infection, the subject can be included. • Screening laboratory values: - Creatinine Clearance < 70 mL/min - Total bilirubin > 2.0 times upper normal limit (unless due to liver involvement of B-CLL) - ALT > 3.0 times upper normal limit (unless due to liver involvement of B-CLL) • Treatment with any non-marketed drug substance or experimental therapy within 4 weeks prior to Visit 1 or currently participating in any other interventional clinical study • Known or suspected inability to comply with a study protocol |
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E.5 End points |
E.5.1 | Primary end point(s) |
To assess the rate of complete and overall response using pentostatin, cyclophosphamide, and ofatumumab in patients with previously untreated CLL requiring therapy |
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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 | No |
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) | 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 | No |
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) | 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 | 9 |
E.8.5 | The trial involves multiple Member States | No |
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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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 | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
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 | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |