A RANDOMIZED, OPEN-LABEL, MULTI-CENTRE STUDY TO EVALUATE PATIENT PREFERENCE WITH SUBCUTANEOUS ADMINISTRATION OF RITUXIMAB VERSUS INTRAVENOUS RITUXIMAB IN PREVIOUSLY UNTREATED PATIENTS WITH CD20+ DIFFUSE LARGE B-CELL LYMPHOMA OR CD20+ FOLLICULAR NON-HODGKIN’S LYMPHOMA GRADES 1, 2 OR 3A

Tahapan Penelitian : Awal
Sponsor:
Mitra Pelaksana:
Hasan Sadikin Hospital; Sardjito Hospital; Dharmais National Cancer Hospital; Surabaya Oncology Hospital
No Registry
INA-NK1QGRZ
Tanggal Input Registry : 13-09-2017

12-04-2013
Primary endpoint For the primary endpoint of patient preference, the proportion of patients who prefer Rituximab SC over Rituximab IV and the corresponding 95% confidence interval will be estimated.
Secondary endpoints Safety will be assessed by AEs, AEs of grade ≥ 3, serious adverse events (SAEs), premature withdrawal from the study and from study medication, laboratory parameters, vital signs and ECOG performance status. Adverse events will be coded in MedDRA. The incidence of AEs and SAEs will be summarized by primary system organ class and preferred term. Laboratory parameters will be presented in shift tables of NCI-CTC grade at baseline against worst grade recorded during each treatment period and overall. Other safety variables will be summarized. The time required for rituximab administration defined as start of rituximab SC injection to end of the injection and start of rituximab IV infusion to the end of the infusion will be summarized. Patient-assessed satisfaction and convenience using RASQ and CTSQ will be summarized and presented by treatment group. Efficacy endpoints: The Complete Response (CR/CRu) rate measured 28 (± 3) days after Day 1 of the last dose of induction treatment will be summarized. The time-to-event endpoints EFS, DFS, PFS and OS from randomization will be summarized overall and by the two treatment sequence groups using the Kaplan Meier approach. Immunogenicity (optional test, as per country requirement) (anti-rituximab and anti-rHuPH20 antibodies) and the associated rituximab concentration level at each anti-rituximab sampling time point will be summarized.
 
A RANDOMIZED, OPEN-LABEL, MULTI-CENTRE STUDY TO EVALUATE PATIENT PREFERENCE WITH SUBCUTANEOUS ADMINISTRATION OF RITUXIMAB VERSUS INTRAVENOUS RITUXIMAB IN PREVIOUSLY UNTREATED PATIENTS WITH CD20+ DIFFUSE LARGE B-CELL LYMPHOMA OR CD20+ FOLLICULAR NON-HODGKIN’S LYMPHOMA GRADES 1, 2 OR 3A
A RANDOMIZED, OPEN-LABEL, MULTI-CENTRE STUDY TO EVALUATE PATIENT PREFERENCE WITH SUBCUTANEOUS ADMINISTRATION OF RITUXIMAB VERSUS INTRAVENOUS RITUXIMAB IN PREVIOUSLY UNTREATED PATIENTS WITH CD20+ DIFFUSE LARGE B-CELL LYMPHOMA OR CD20+ FOLLICULAR NON-HODGKIN’S LYMPHOMA GRADES 1, 2 OR 3A
Observasional
This will be an open-label, randomized study and therefore treatment allocation will not be concealed. Eligible patients will be randomly allocated to Treatment Arm A (rituximab SC → rituximab IV) or Arm B (rituximab IV → rituximab SC) with a 1:1 ratio before dosing on Day 1 of Cycle 1. Randomization will occur using a centralized IxRS. Patients will be stratified according to age (
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Inclusion Criteria:

1. Signed, written informed consent form 2. Age ≥ 18 and ≤ 80 years at time of randomization 3. Histologically confirmed, previously untreated CD20+ DLBCL or CD20+ follicular NHL Grade 1, 2 or 3a, according to the WHO classification system. Note: lymph node excision or adequate core biopsy is required for the diagnosis of DLBCL or follicular NHL. Fine-needle aspiration samples should not be used as the sole material for pathological diagnosis. 4. An IPI score of 1-4 or IPI score of 0 with bulky disease, defined as one lesion ≥ 7.5 cm, or FLIPI (low, low-intermediate, high-intermediate, high) 5. At least one bi-dimensionally measurable lesion defined as ≥ 1.5 cm in its largest dimension on CT scan

Exclusion Criteria:

Cancer-Related Criteria 1. Transformed lymphoma or FL IIIB 2. Primary CNS lymphoma, histologic evidence of transformation to a Burkitt lymphoma, primary mediastinal DLBCL, primary effusion lymphoma, primary cutaneous DLBCL or primary DLBCL of the testis 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 enrolment. 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. Prior therapy for DLBCL or follicular NHL, with the exception of nodal biopsy or local irradiation Note: lymph node excision or adequate core biopsy is required for the diagnosis of DLBCL or follicular NHL. Fine-needle aspiration samples should not be used as the sole material for pathological diagnosis. 5. Prior treatment with cytotoxic drugs (with the exclusion of intrathecal methotrexate for CNS prophylaxis in DLBCL) or rituximab for another condition (e.g., rheumatoid arthritis) or prior use of an anti-CD20 antibody 6. Prior use of any monoclonal antibody within 3 months prior to randomization 7. Chemotherapy or other investigational therapy within 28 days prior to randomization 8. 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 5 days) is acceptable for patients with aggressive NHL. Laboratory Assessments at Screening 9. 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 10. Inadequate hematologic function, defined as: - Haemoglobin < 9 g/dL - Absolute neutrophil count < 1.5 x 109/L - Platelet count < 75 x 109/L Note: no transfusions are allowed within 2 weeks prior to the start of study drug administration. 11. Inadequate hepatic function, defined as: - aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 2.5 x the ULN - total bilirubin ≥ 1.5 x the ULN. Note: patients with documented Gilbert disease may be enrolled if total bilirubin is ≤ 3.0 x the ULN. Other Prior or Current Medical Conditions or Treatments 12. History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies or known sensitivity or allergy to murine products 13. For patients with DLBCL - Contraindication to any of the individual components of CHOP (cyclophosphamide, vincristine, doxorubicin and prednisone), including prior receipt of anthracyclines 14. 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). 15. Recent major surgery (within 4 weeks prior to randomization), other than for diagnosis 16. 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 randomization 17. Active hepatitis B virus (HBV) or active hepatitis C virus (HCV) infection (must be ruled out during screening). Patients with occult or prior HBV infection (defined as positive total hepatitis B core antibody (HBcAb) and negative or positive HBsAg with undetectable HBV deoxyribonucleic acid [DNA]) may be included but these patients must be followed closely (see Section 4.5.1.8). Patients who are positive for HBsAg and are PCR negative must be treated with lamivudine (or other standard antiviral therapy) beginning prior to the initiation of study treatment and continuing for 6 months after completing study treatment. Patients positive for HCV antibody are eligible only if polymerase chain reaction (PCR) testing for HCV ribonucleic acid (RNA) is negative. 18. History of HIV seropositive status. General Criteria 19. Inability to provide informed consent. Furthermore, any patients who cannot read and/or write will require an independent to help complete the questionnaires. 20. Life expectancy of less than 6 months 21. A positive serum pregnancy test in women of childbearing potential within 7 days prior to randomization or within 14 days if with a confirmatory urine pregnancy test within 7 days prior to randomization. Women of childbearing potential are defined as pre-menopausal women or women who are < 2 years after the onset of menopause and are not surgically sterile. 22. Fertile men or women of childbearing potential who do not agree to use a highly effective measure of contraception (such as oral contraceptives, intrauterine device or barrier method of contraception in conjunction with spermicidal jelly or surgically sterile) throughout the study and for at least 12 months after the last dose of rituximab.
 
241/UN6.C2.1.2/KEPK/PN/2012 dated 18 Dec 2012; KE/FK/869/EC dated 20 Nov 2012; 03/PEP/01/2013 dated 8 Jan 2013; 001/RSOS/Ext./XII/2012 dated 05 Dec 2012
NA
PN.01.06.1.31.01.13.440 dated 17 Jan 2013; PN.01.06.1.31.01.13.441 dated 17 Jan 2013; PN.01.06.1.31.01.13.324 dated 29 Jan 2013; PN.01.06.1.31.04.13.2265 dated 19 Apr 2013
MO28457
Rachmat Sumantri; Djohan Kurnianda; Ronald Hukom; Ami Ashariati