Previously untreated patients with CD20-positive follicular lymphoma, Grade 1, 2 or 3a according to the WHO 2008 classification system. MedDRA version: 14.1 Level: LLT Classification code 10059432 Term: Follicular mixed small and large cell lymphoma System Organ Class: 100000004864
Conditions
Interventions
Product Name: Rituximab
Product Code: MK-8808
Pharmaceutical Form: Concentrate for solution for injection/infusion
INN or Proposed INN: RITUXIMAB
Sponsors
Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Patient understands the study procedures, alternative treatments available, the risks involved with the study, and agrees to participate by giving informed consent. 2. Patient is male or female, and =18 years of age on the day of signing informed consent. 3. Patient has a life expectancy >3 months with no expected need of immediate intervention to treat life threatening complications. 4. Patient has a histological diagnosis of CD20-positive follicular lymphoma, Grade 1, 2 or 3a according to the WHO 2008 classification system (see Appendix 6.3), the biopsy must be comprised of 6 cm in its greatest diameter) - Symptomatic enlargement of spleen or liver Vital organ compression - Ascites or pleural effusion - Cytopenia secondary to lymphoma - B symptoms (e.g. fever >38°C without infection; drenching night sweats; unexplained loss of >10% body weight within the preceding 6 months) 6. Patient has at least one bi-dimensionally measureable lesion and that lesion must not have been previously irradiated. 7. Patient has Eastern Cooperative Oncology Group (ECOG) performance status =2 (see Appendix 6.2). 8. Female patients of childbearing potential (defined as women who have not been surgically sterilized or have not been free from menses for > 2 years) have a negative urine pregnancy test within 72 hours prior to receiving the first dose of study medication. Are the trial subjects under 18? no Number of subjects for this age range: 0 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 260 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 206
Exclusion criteria
Exclusion criteria: 1. Number of circulating lymphatic cells >10,000/mcL. 2. Presence or history of CNS involvement (either CNS lymphoma or lymphomatous meningitis). 3. Prior systemic therapy for FL, including but not limited to chemotherapy, anti- CD20 compounds, immunotherapy and any other type or class of anti-cancer drugs. 4. Prior therapy with an anthracycline (e.g., doxorubicin, epirubicin, liposomal doxorobucin). 5. Radiotherapy within 2 months prior to Cycle 1 Day 1, except involved field irradiation of up to two lesions that will not be used to evaluate disease progression. 6. Patient has a known hypersensitivity to any of the drugs required in this study or to any of the excipients or to murine proteins. 7. Patient with a history of a prior malignancy, with the exception of cervical intraepithelial neoplasia; basal cell carcinoma of the skin; or who has undergone therapy with curative intent with no evidence of disease recurrence for five years. 8. Patient is currently participating or has participated in a study with an investigational compound within 30 days prior to Cycle 1 Day 1. 9. Patient has any medical contra-indication for prednisone as being dosed in the CHOP chemotherapy regimen. 10. Patient is in a severely immunocompromised state. 11. Patient has poorly controlled diabetes mellitus. 12. Patient has Grade =2 peripheral neuropathy. 13. Patient has one of the following: a. Is HIV-positive b. Is positive for Hepatitis B surface antigen (HBsAg+) or antibodies to Hepatitis B core antigen (anti-HBcAg+) c. Has antibodies to Hepatitis C virus 14. Patient has an active infection, including but not limited to tuberculosis. 15. Patient has severe cardiovascular disease, cardiac heart failure, unstable cardiovascular conditions including recent myocardial infarction, angina, arrhythmias or uncontrolled hypertension.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To compare the CR+CRu rate of MK-8808 plus CHOP versus MabThera plus CHOP at week 20 (+/- 1 week) after randomization.;Secondary Objective: 1. To compare MK-8808 plus CHOP versus MabThera plus CHOP with respect to: - Overall Response Rate (CR + CRu + PR at 20 weeks) - Progression Free Survival - Time-to Treatment Failure - Overall Survival 2. To compare MK-8808 plus CHOP versus MabThera plus CHOP with respect to: - Safety - Depletion of CD19-positive B cells - Immunogenicity 3. To evaluate efficacy (CR+CRu rate and secondary endpoints) and safety in patients with the 158V/V, 158V/F and 158F/F germ line genotypes of the Fc?RIIIa receptor.;Primary end point(s): CR+CRu rate: is defined as the proportion of patients who achieve a complete response or unconfirmed complete response per centrally assessed IWG 1999 criteria [25]. LIST OF SAFETY MEASUREMENTS (Refer to the Study Flow Charts in Section 1.7 of the study protocol for time points and other details regarding these measurements.): - Evaluation of adverse experiences - PE - Vital signs - ECOG Performance Status (see Appendix 6.2) - CBC & Blood Chemistry (see Appendix 6.1) - CD19-positive B-cells - Serum immunoglobulins - ECHO or MUGA;Timepoint(s) of evaluation of this end point: The primary endpoint will be assessed when all patients have either completed the week 20 CT scan assessment, plus or minus 1 week from randomization, or discontinued the study. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - Overall response rate (Overall RR): is defined as the proportion of patients who achieve a complete response, an unconfirmed complete response, or a partial response (CR+CRu+PR) per centrally assessed IWG 1999 criteria [25]. - Progression Free Survival (PFS): is defined as the time from randomization to documented progressive disease by centrally assessed IWG 1999 criteria [25] or death, whichever occurs first. Please see 3.5.5.1 for the definition of censoring for the endpoint. - Time-to Treatment Failure (TTF): is defined as the time from randomization to discontinuation of treatment for any reason, including disease progression (by centrally assessed IWG 1999 criteria [25], treatment toxicity, and death. - Overall Survival (OS): is defined as the time from randomization to death due to any cause. Patients without documented death at the time of analysis will be censored at the date last known to be alive.;Timepoint(s) of evaluation of this end point: The secondary endpoints will be assessed when all patients have either completed the week 20 CT scan assessment, plus or minus 1 week from randomization, or discontinued the study. | — |
Countries
Argentina, Australia, Belarus, Brazil, Canada, Chile, China, Croatia, Egypt, Georgia, India, Israel, Italy, Korea, Republic of, Malaysia, Mexico, New Zealand, Peru, Philippines, Russian Federation, Singapore, South Africa, Taiwan, Thailand, Ukraine
Contacts
Public ContactGlobal Clinical Trials Operations
Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.
Outcome results
None listed