An open-label, multi-centre, dose escalating, phase I/randomized phase II study to investigate the safety and tolerability of RO5072759 given as monotherapy in patients with CD20+ malignant disease.
- Conditions
- Patients with relapsed CD20+ indolent NHL will be enrolled (Relapsed defined asrelapsed indolent lymphoma with documented history of response [CR, CRu, or PR) of=6 months in duration from the completion of last rituximab containing regimen at some point in a patients treatment history).MedDRA version: 9.1Level: LLTClassification code 10029547Term: Non-Hodgkin's lymphoma
- Registration Number
- EUCTR2008-003460-19-BE
- Lead Sponsor
- F.Hoffmann-La Roche
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 220
Patients in the phase II (including those in the SDI) part of the study must meet the following criteria:
1. Have history of histologically confirmed CD20+, indolent B-cell NHL (any grade). This includes small lymphocytic lymphoma and marginal zone lymphoma but exclude B-CLL. For each patient, a prior biopsy demonstrating CD20 positivity of tumor cells must be available locally at the investigator site (review performed according to local standard procedures), prior to dosing, and will be further confirmed following central pathology review after dosing. A biopsy must be performed if transformation is suspected.
2. Have a clinical indication for treatment as determined by the investigator.
3. Relapsed disease with documented history of response (CR, CRu, or PR) of =6 months in duration from completion of last rituximab containing regimen. A rituximab-containing regimen is defined as rituximab as a single agent during induction and/or maintenance, or in combination with other agents during induction and/or maintenance.
4. All patients must have at least one bi-dimensionally measurable lesion (>1.5 cm in its largest dimension by computerized tomography [CT] scan). Note that all measurable and evaluable disease must be assessed and documented prior to initiation of RO5072759/rituximab treatment. Tumor response will be based on the status of all areas of disease.
5. ECOG performance status: of 0-2
All patients (Phase I and II) must also meet the following criteria to be eligible for study entry:
6. Able and willing to provide written informed consent and to comply with the study protocol
7. Age =18 years
8. Life expectancy of =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
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range
Patients who meet any of the following criteria will be excluded from the study:
1. Prior use of any investigational monoclonal antibody within 6 months of study start.
2. Prior administration of rituximab within 56 days of study entry or 3 months for any radioimmunotherapy.
3. History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies. Known sensitivity or allergy to murine products.
4. Central nervous system lymphoma or histological evidence of transformation to high grade or diffuse large B-cell lymphoma (if transformation is clinically suspected a re-biopsy is mandatory).
5. 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.
6. 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).
7. Known active bacterial, viral (including human immunodeficiency virus [HIV], ( HCV, HBV, HTLV I), fungal, mycobacterial, or other infection (excluding fungal infections of nail beds) or any major episode of infection requiring hospitalization or treatment with IV antibiotics (relating to the completion of the course of antibiotics) within 4 weeks of 1st dose of RO5072759 or rituximab.
8. Recent major surgery (within 4 weeks prior to screening), other than for diagnosis.
9. Unless clearly due to lymphoma any of the following abnormal laboratory values (Note 5% window allowed for inter-laboratory variation per protocol):
• Renal – Calculated creatinine clearance by Cockcroft-Gault formula =50 mL/min
• Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >2.5 times the upper limit of normal.
• Platelet count <75 × 109/L.
• Neutrophils <1.5 × 109/L
• Hemoglobin <10g/dL
10. Presence of positive test results for any of the following: all of the first 5 tests should be done for all patients
• 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.
• Human T-lymphotropic virus 1 [HTLV I] (in endemic countries only)
11. Women who are pregnant or lactating.
12. 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 RO5072759 or rituximab.
13. Ongoing corticosteroid use, with the exception of corticosteroid use for other indications, is permitted only up to a maximum dose of 30 mg/day prednisone or equivalent.
14. Treatment with an investigational agent or participation a clinical study 30 days prior to study day 1.
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