A single arm, multicentre, phase IIIb study to evaluate safety, efficacy and pharmacokinetic (PK) of subcutaneous (SC) rituximab administered during induction phase or maintenance in previously untreated patients with CD20+ diffuse large B cell lymphoma (DLBCL) or follicular lymphoma (FL)
- Conditions
- CD20+ diffuse large B-cell lymphoma or CD20+ follicular non-Hodgkin’s lymphoma grade 1, 2 or 3aTherapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]
- Registration Number
- EUCTR2013-000647-12-IT
- Lead Sponsor
- ROCHE S.p.A.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 158
Patients must meet the following criteria for Study entry:
1. Signed, written informed consent form
2. Age = 18 and = 80 years at time of enrolment
Rituximab – Roche S.p.A.
Protocol ML28881 (MABRELLA) - Version 1, 18 March 2013 45
3. Histologically confirmed, CD20+ DLBCL or CD20+ follicular NHL grade 1, 2 or 3a, according to the WHO classification system
4. Currently being treated with rituximab IV in the Induction or Maintenance setting, having received at least one full dose of rituximab IV, defined as standard full dose of rituximab IV 375 mg/m2 administered without interruption or early discontinuation because of tolerability issues
5. Expectation and current ability for the patient to receive at least four additional cycles of treatment during the Induction phase or six additional cycles of treatment during the Maintenance phase (patients with follicular NHL)
6. Induction only: An International Prognostic Index (IPI) score of 1-4 or IPI score of 0 with bulky disease, defined as one lesion = 7.5 cm, or Follicular Lymphoma International Prognostic Index (FLIPI) (low, intermediate or high risk) (see Appendix 4)
7. Induction only: At least one bi-dimensionally measurable lesion defined as = 1.5 cm in its largest dimension on computed tomography (CT) scan
8. Eastern Cooperative Oncology Group (ECOG) performance status = 3 (see Appendix 4)
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 130
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 30
Patients who meet any of the following criteria will be excluded from Study entry:
Cancer-Related Criteria
1. Transformed lymphoma or follicular lymphoma (FL) IIIB
2. Primary central nervous system lymphoma, histologic evidence of transformation to a Burkitt lymphoma, primary effusion lymphoma, primary mediastinal DLBCL, DLBCL of the testis, or primary cutaneous DLBCL
3. History of other malignancy that could affect compliance with the protocol or interpretation of results. This includes a malignancy that has been treated but not with curative intent, unless the malignancy has been in remission without treatment for = 5 years prior to dosing. Note: Patients with a history of curatively treated basal or squamous cell carcinoma or melanoma of the skin or in situ carcinoma of the cervix are eligible for the Study.
Prior or Concomitant Treatments
4. Ongoing corticosteroid use > 30 mg/day of prednisone or equivalent.
Note: (i) patients receiving corticosteroid treatment with = 30 mg/day of prednisone or equivalent must be on a documented stable dose of at least 4 weeks duration prior to randomization; (ii) a pre-phase of high dose prednisolone (e.g. 100 mg/day for 3 to 5 days) is acceptable for patients with aggressive NHL.
Laboratory Assessments at Screening
5. Inadequate renal function, defined as:
- Creatinine > 1.5 times the upper limit of normal (ULN) (unless normal creatinine clearance), or calculated creatinine clearance < 40 mL/min (using the Cockcroft-Gault formula)
6. Inadequate hematologic function, defined as:
- Haemoglobin < 9 g/dL
- Absolute neutrophil count < 1.5 x 109/L
- Platelet count < 75 x 109/L
7. Inadequate hepatic function, defined as:
- Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 2.5 x ULN
- Total bilirubin = 1.5 x ULN. Note: patients with documented Gilbert disease may be enrolled if total bilirubin is = 3.0 x ULN
Other Prior or Current Medical Conditions or Treatments
8. History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies or known sensitivity or allergy to murine products
9. For patients with DLBCL - Contraindication to any of the individual components of CHOP (cyclophosphamide, vincristine, doxorubicin and prednisone), including prior receipt of anthracyclines
10. Other serious underlying medical conditions, which, in the Investigator‘s judgment, could impair the ability of the patient to participate in the Study (e.g., significant cardiovascular disease, uncontrolled diabetes mellitus, gastric ulcers, active autoimmune disease)
11. Recent major surgery (within 4 weeks prior to dosing, other than for diagnosis
12. Active and/or severe bacterial, viral, fungal, mycobacterial, parasitic, or other infection (excluding fungal infections of nail beds) or any major episode of infection requiring treatment with IV antibiotics or hospitalization (relating to the completion of the course of antibiotics except if for tumour fever) within 4 weeks prior to dosing
13. Active hepatitis B virus (HBV) or active hepatitis C virus (HCV) infection (must be ruled out during screening):
- Positive test results for chronic hepatitis B infection (defined as positive HBsAg serology)
Patients with occult or prior hepatitis B infection (defined as positive total hepatitis B core antibody [HBcAb] and negative or positive HBsAg with HBV DNA undetectable) may be included. These patients must be followed closely.
Patients need to receive antiviral
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