A Dose-Escalating Study of RO5072759 in Patients With CD20+ Malignant Disease
- Conditions
- For the phase I and II parts of the study, patients with CD20+ malignant disease for whom no therapy of higher priority is available and where treatment with an anti-CD20 antibody is deemed appropriate will be enrolled.For the phase II part of the study, patients with either, relapsed/refractory CD20+ indolent NHL, relapsed/refractory aggressive NHL and relapsed/refractory B-CLL will be enrolled.MedDRA version: 14.1Level: LLTClassification code 10024340Term: Leukemia lymphocytic chronicSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 14.1Level: LLTClassification code 10025311Term: Lymphoma (non-Hodgkin's)System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2007-001103-37-DE
- Lead Sponsor
- F. Hoffmann-La Roche Ltd
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 134
Patients in the Phase I part of the study must meet the following criteria: 1. Have documented CD20+ malignant disease (B-cell lymphoma or B-CLL [B-CLL confirmed by NCI Working Group Criteria, 2008) for which no therapy of curative or high priority exists and for whom treatment with an anti-CD20 antibody may be appropriate. For each patient, a prior biopsy demonstrating CD20 positivity of tumour cells must be available locally prior to dosing, and will be further confirmed following central review (For B-CLL patients confirmation of CD20+ status must be performed by flow cytometry. Patients with small lymphocytic lymphoma [SLL], must have CD20+ status confirmed by histopathological evaluation of a lymph node biopsy). Ideally, where feasible during the course of the study, confirmation that the disease remains CD20+, should be obtained (Fine needle aspiration cytology [FNAC] is sufficient for this purpose where feasible). In addition, where available, the initial diagnostic biopsy will also be reviewed centrally. 2. Have either: • Relapsed or refractory indolent NHL • Relapsed or refractory aggressive NHL • Relapsed or refractory B-CLL 3. All patients (NHL and B-CLL) must have at least one bi-dimensionally measurable lesion (>1.5 cm in its largest dimension by computerized tomography [CT] scan). In addition, where appropriate, for CLL patients, circulating lymphoctye cell assessments will be performed. Note that all measurable and evaluable disease must be assessed and documented prior to initiation of RO5072759 treatment. Tumor response will be based on the status of all areas of disease. Patients in both Phase I and II parts of the study must also meet the following criteria to be eligible for study entry: 4. Able and willing to provide written informed consent and to comply with the study protocol. 5. Have a clinical indication for treatment as determined by the investigator 6. Age >18 years. 7. ECOG performance status of 0-2 8. Life expectancy >12 weeks
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 70
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 64
Patients in both Phase I and II portions who meet any of the following criteria at screening will be excluded from the study: 1. Prior use of any investigational monoclonal antibody therapy or other agent within 6 months of study start 2. Prior use of any anti-cancer vaccine 3. Prior use of standard anti-lymphoma/leukemia therapy or radiation therapy within 4 weeks of enrollment 4. Prior administration of rituximab within 56 days of study entry. However, for those patients with aggressive disease (DLBCL and MCL) and any other patient, where immediate treatment is mandated, a rituximab wash-out period of 28 days will be considered acceptable. This will be approved by the Sponsor on a case by case basis. 5. Prior administration of radioimmunotherapy 3 months prior to study entry 6. History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies. Known sensitivity or allergy to murine products. 7. Central nervous system lymphoma 8. History of other malignancy which could affect compliance with the protocol or interpretation of results. Patients with a history of malignancy that has been treated, but not with curative intent, will also be excluded, unless the malignancy has been in remission without treatment for =2 years prior to enrollment. 9. Evidence of significant, uncontrolled concomitant diseases which could affect compliance with the protocol or interpretation of results, including significant cardiovascular disease (such as New York Heart Association Class III or IV cardiac disease, myocardial infarction within the last 6 months, unstable arrhythmias, or unstable angina) or pulmonary disease (including obstructive pulmonary disease and history of symptomatic bronchospasm). 10. Known active bacterial, viral (including human immunodeficiency virus [HIV]), fungal, mycobacterial, or other infection (excluding fungal infections of nail beds) or any major episode of infection requiring hospitalization or treatment with IV antibiotics (for IV antibiotics this pertains to completion of last course of antibiotic treatment) within 4 weeks of receiving the first dose of RO5072759 11. Recent major surgery (within 4 weeks prior to receiving first dose of RO5072759), other than for diagnosis. 12. Any of the following abnormal laboratory values: Renal – Calculated creatinine clearance by Cockcroft-Gault formula = 50 mL/min for NHL patients, or = 60 mL/min for the first 3 B-CLL patients enrolled in cohort 4b (See Appendix 5). The restriction of = 60 mL/min for the first 3 B-CLL patients, may be modified for subsequent cohorts (i.e., reduced or increased) based upon review of the ongoing safety data but the calculated creatinine clearance should not be = 50 mL/min. 13. Presence of positive test results for: - Human immunodeficiency virus (HIV), - Hepatitis B (HB virus [B DNA], HB surface antigen [HBsAg], total HB core antibody [anti-HB-c] - Hepatitis C (Hepatitis C virus [HCV] antibody serology testing. 14. Women who are pregnant or lactating. 15. Fertile men or women of childbearing potential unless (1) surgically sterile or (2) using an adequate measure of contraception such as oral contraceptives, intrauterine device, or barrier method of contraception in conjunction with spermicidal jelly. Effective contraception is required throughout the study and (because of the long half-life of humanized monoclonal antibodies and the potential for prolonged lymphopenia) for at least 12 months after the last dose of RO5072
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method