CTRI/2018/07/014885 [Registered on: 16/07/2018] Trial Registered Prospectively
Last Modified On:
13/09/2022
Post Graduate Thesis
No
Type of Trial
Interventional
Type of Study
Biological
Study Design
Randomized, Parallel Group, Active Controlled Trial
Public Title of Study
Safety and efficacy assessment of Rituximab (Zydus) in comparison with Rituximab (Roche/Genentech) in Patients with Diffuse Large B Cell Lymphoma (DLBCL)
Scientific Title of Study
Randomized, Assessor-Blind, Multicentre, Parallel Group, Two Arms, Clinical Study to Assess the Efficacy, Pharmacokinetics, Pharmacodynamics, Immunogenicity and Safety of Rituximab (Test Product, Zydus) in comparison with Rituximab (Reference Product, Roche/Genentech) in Patients with Diffuse Large B Cell Lymphoma (DLBCL)
Trial Acronym
Secondary IDs if Any
Secondary ID
Identifier
RITU.17.001.01 PROTOCOL Version 1.0 dated 05.02.2018
Protocol Number
Details of Principal Investigator or overall Trial Coordinator (multi-center study) Modification(s)
Name
Dr Manjunath K
Designation
Deputy General Manager
Affiliation
Cadila Healthcare Ltd
Address
Zydus Research Centre,
Survey No. 396/403, Sarkhej-Bavla National Highway No.8A
Moraiya, Ahmedabad 382213, India
Shree Himalaya Cancer Hospital & Research Institute
No 4 Vinod Baug, B/H Railway Station ,
Jetalpur Bridge,
Alkapuri , Vadodara Gujarat - 390020 Vadodara GUJARAT
9427432642
jainkartikeya@rocketmail.com
Dr Ghanshyam Biswas
Sparsh Hospital and Critical care Private Limited
Plot No A/407 , Sahid Nagar,
Bhubaneswar, - 751007 , Odisha,
India
Khordha ORISSA
9937500878
drgbiswas@gmail.com
Dr KC Lakshmaiah
Srinivasam Cancer Care Multispecialty Hospitals India Pvt Ltd.,
No 36 1st A main road,
5th cross Nethravathi Street, Maruthi Nagar,
Nagarbhavi Main Road,
Bangalore -560072, Karnataka, India.
Bangalore KARNATAKA
9448055949
kcluck@gmail.com
DrDeepan Rajamnickam
Thangam Hospital and Thangam Cancer Center,
No. 54, Dr. Sankaran Road,
Namakkal – 637001, Tamilnadu, India
Namakkal TAMIL NADU
9619163678
deepan_rm@yahoo.co.in
Dr Ankit Patel
Unique Hospital- Multispeciality & Research Institute
"Unique Hospital- Multispeciality & Research Institute
Opp. Kiran Motor, Nr. Canal, Civil Hospital Char Rasta- Sosyo Circle Lane, Off Ring Road, Surat- 395002, Gujarat, India." Surat GUJARAT
9825404202
drankitoncologist@gmail.com
Dr P Vijay Veeran
Universal Cancer Hospital
No. 370, Kondalampatti Roundana,
Salem – 636010
Salem TAMIL NADU
9842821480
drvijayaveeran@gmail.com
Dr Amit Jain
Valentis Cancer Hospital
Clinical Research Room, Ground floor, Valentis Cancer Hospital, Mussoouri Mawana Road, Meerut-250001 Meerut UTTAR PRADESH
"Ethics Committee Unique Hospital- Multispeciality & Research Institute Opp. Kiran Motor, Nr. Canal, Civil Hospital Char Rasta- Sosyo Circle Lane, Off Ring Road, Surat- 395002, Gujarat, India."
Approved
"Institutional Ethics Committee Kailash Cancer Hospital and Research Center Goraj-391760. Waghodia, Vadodara, Gujarat, India"
Approved
"Manavata Clinical Research Institute Ethics Committee Curie Manavata Cancer Centre Opp Mahamarg Bus Stand, Mumbai Naka Nashik , 422004. Maharashtra, India."
Approved
adhar Institutional Ethics Committee
Approved
Bhakti Vedanta Hospital Ethics Committee
Approved
Ethics Committee – Silver, Office of Research Carman Block – First Floor, Christian Medical College Vellore – 632004, Tamilnadu
Approved
Ethics Committee N.R.S. Medical College 138- A.J.C, Bose Road and, Kolkata – 700014
Approved
Ethics Committee Netaji Subhash Chandra Bose cancer Hospital 3081,Nayabad, New Garia, Kolkata-700094 West Bangal
Approved
GVN Institutional Ethics Committee No.46, Singarathope, Trichy-620008, Tamilnadu, India
Approved
HCG Multi Specialty Ethics Committee HCG Multi Specialty Hospital , Mithakhali, Ellis bridge , Ahmedabad 380060
Approved
HCG Vadodra Ethics Committee, HCG Cancer Centre, Sun Pharma Road, Opp Satsang Party Plot, Vadodra-390012.
Instituional Ethics Committee of Sai Sneh Hospital and Diagnostic Centre, opp PMT Bus Depot, Pune-Satara Road, Katraj, Pune-411046, Maharashtra.
Approved
Instituional Ethics Committee of Sai Sneh Hospital and Diagnostic Centre, opp PMT Bus Depot, Pune-Satara Road, Katraj, Pune-411046, Maharashtra.
Approved
Institutional Ethics Committee Meenakshi Mission Hospital and Research Centre , Lake Area ,Melur Road ,Madurai Tamilnadu -625107 India
Approved
Institutional Ethics Committee Sapthagiri Institute of Medical Sciences & Research Centre No. 15, Chikkasandra, Hesaraghatta Main Road, Bengaluru -560090, Karnataka
Approved
Institutional Ethics Committee Apex Hospital Pvt. Ltd. SP-4 & 6, MIA , Malviya Nagar Near Apex Circle Jaipur, Rajasthan 302017
Approved
Institutional Ethics Committee Chittaranjan National cancer Institute 37 S.P. Mukherjee Road Kolkata-700026 West Bengal India
Approved
Institutional Ethics Committee Department of Pharmacology Government Medical College and Hospital Medical College Square Road Nagpur
Approved
Institutional Ethics Committee Institute of Medical sciences(IMS) ) and SUM Hospital K-8, Kalinga Nagar Bhubaneswar-751003 Odisha , India
Approved
Institutional Ethics Committee Lata Mangeshkar medical foundation’s , Deenanath Mangeshkar Hospital and Research Center, Erandawane, Pune 411004, India
Approved
Institutional Ethics Committee Maulana Azad Medical College
Approved
Institutional Ethics Committee of Mysore Medical College & Research Institute and Associated Hospital , Mysore – 570021
Approved
Institutional Ethics Committee Poona Medical Research Foundation
Approved
Institutional Ethics Committee Sanjeevani Cancer Hospital
Approved
Institutional Ethics Committee Shree Himalaya Cancer Hospital & Research Institute No 4 Vinod Baug, B/H Railway Station , Jetalpur Bridge, Alkapuri , Vadodara Gujarat – 390020
Approved
Institutional Ethics Committee Valentis Cancer Hospital Mussoorie Mawana Road Meerut Meerut Uttar Pradesh - 250001 India
Approved
Institutional Ethics Committee, Sparsh Hospital and Critical care Private Limited
Approved
Institutional Review Board Rajiv Gandhi cancer institute and research centre centre Sector 5, Rohini New Delhi 110085 India
SCCMH-Institutional Ethics Committee No.36, 1st Main Road, 5th Cross Nethravathi Street Maruthi Nagar, Nagarbhavi Main Road, Bangalore -560072, Karnataka, India.
Approved
SEAROC Ethics Committee
Approved
Thangam Hospital-Institutional Ethics Committee(TH-IEC), 54, Dr. Sankaran Road, Namakkal-637001, Tamilnadu, India
Approved
Universal Hospital, (A Unit of Universal Cancer Hospital Ltd)- Institutional Ethics Committee.No.370, Kondalampatty Roundana, Salem-630010,
Diffuse Large B Cell Lymphoma (DLBCL), (1) ICD-10 Condition: C859||Non-Hodgkin lymphoma, unspecified,
Intervention / Comparator Agent
Type
Name
Details
Comparator Agent
Rituximab (Roche/Genentech)
Dosage: 375 mg/m2 intravenous infusion,
every 3 weeks on day 1 of CHOP regimen for total 6 cycles
Intervention
Rituximab (Zydus)
Dosage: 375 mg/m2 intravenous infusion,
every 3 weeks on day 1 of CHOP regimen for total 6 cycles
Inclusion Criteria
Age From
18.00 Year(s)
Age To
65.00 Year(s)
Gender
Both
Details
1.The patient willing to give written, signed, and dated informed consent to participate in the study before initiating any study related procedures
2.Male or non-pregnant, non-lactating Female ≥18 years and ≤65 years of age (both inclusive)
3.Patients with at least one measurable lesion as per International Working Group Revised Response Criteria for Malignant Lymphoma
4.Untreated Newly diagnosed patients with a confirmed pathologic diagnosis of CD20+ large B cell-non-Hodgkin’s lymphoma (DLBCL).
5.Stage II-III or IV defined by the referring physician on the basis of the Cotswolds modification of the Ann Arbor classification.
6.Age-adjusted International Prognostic Index (IPI) score 0 or 1
7.Patients who are eligible for receiving Rituximab and CHOP
8.Patient must have an adequate bone marrow, renal, cardiac and hepatic function
a.Bone marrow reserve:
i.ANC ≥ 1500/mm3
ii.Platelet count ≥ 100,000/mm3
iii.Hemoglobin ≥ 9.0 g/dL
b.Renal Function: Serum Creatinine ≤ 1.5 times ULN
c.Hepatic Function:
i.Total bilirubin ≤1.5 × upper limit of normal (ULN); except if elevation is due to Gilbert’s Syndrome with transitory elevations of indirect bilirubin.
ii.Alkaline phosphatase, alanine transaminase, and/or aspartate transaminase ≤3 × ULN or ≤5 × ULN in patients with liver involvement.
d.Left Ventricular Ejection Fraction (LVEF) ≥50% determined by either ECHO or MUGA Scan
9.Subjects with a performance status of 0 to 2 according to the Eastern Cooperative Oncology Group (ECOG)
10.If capable of reproduction, patients and their partners must use contraceptive methods during the full duration of the study and for 12 months after discontinuation of study.
ExclusionCriteria
Details
1.Patient who has a history of hypersensitivity reactions with murine proteins or planned chemotherapy.
2.Bulky Disease (>10 cm on maximum dimension) or involves >1/3 of chest diameter (on radiographic imaging)
3.Patient with severely immunocompromised state.
4.Patient treated with prior therapies including but not limited to Anthracyclines, Rituximab, any other anti-CD-20 therapy or autologous or allogeneic stem cell transplantation
5.Any radiotherapy given for lymphoma or non-lymphoma before 30 days of randomization
6.Patients depending on systemic steroids for Non Lymphomatous condition
7.Subjects with CNS involvement or CNS lymphoma (Diffuse large B-cell lymphoma that is primary CNS, effusional, or intravascular according to the WHO, 2008 classification)
8.Patients with an active, severe infection (e.g., tuberculosis, sepsis and opportunistic infections).
9.Cardiac contra-indication to Doxorubicin therapy: noncompensated heart failure, dilated cardiomyopathy, coronary heart disease with ST segment depression on electrocardiogram (ECG), myocardial infarction in the last 6 months.
10.Neurologic contra-indication to Vincristine as it is indicated in the SmPC: (e.g. peripheral neuropathy).
11.Chronic lung disease with hypoxemia (SpO2 Ë‚ 90%).
12.Severe uncontrolled hypertension (blood pressure more than 150/100 mm Hg), despite optimal medical treatment.
13.Severe uncontrolled diabetes mellitus (As defined by American Diabetes Association), despite optimal medical treatment.
14.Major surgery within 4 weeks of study start (i.e., randomisation)
15.Any other malignancy in the last 5 years other than Non-Hodgkin’s Lymphoma except skin cancer or carcinoma in situ of the cervix
16.Known History of drug addiction within last 1 year
17.The receipt of an investigational medicinal product or participation in other drug research study within a period of 30 days prior to the first dose of investigational medicinal product for the current study.
18.Any history or presence of clinically significant cardiovascular, respiratory, hepatic, renal, hematologic, gastrointestinal, endocrine, immunologic, dermatologic ,neurologic, or psychiatric disease or any other condition which in the opinion of the investigator could jeopardize the safety of the subject or the validity of the study results
19.Receipt of live vaccine within 4 weeks prior to study drug administration
20.Pregnant or breast-feeding patients (for female patients of child bearing potential)
Method of Generating Random Sequence
Not Applicable
Method of Concealment
Not Applicable
Blinding/Masking
Open Label
Primary Outcome
Outcome
TimePoints
Overall Response Rate (i.e., CR + PR) by using International Working Group Response Criteria for Malignant Lymphoma
Timeframe: Baseline & at the end of cycle 6
Secondary Outcome
Outcome
TimePoints
1.Overall Response Rate
2.Assessment of Pharmacokinetic parameters
3.Assessment of Ctrough of Serum Rituximab
4.Assessment of Pharmacodynamic parameters
5.Comparison of Immunogenicity
6.Evaluation of safety
1.Baseline & End of Cycle 3
2.Cycle 1 & 6
3.At the end of each cycle
4. Baseline & at the end of Cycle 1, 3 and 6
5.Baseline & at the end of cycle 3, 6 & Follow up 1, 2, 3.
6.Throughout the Study
Target Sample Size
Total Sample Size="153" Sample Size from India="153" Final Enrollment numbers achieved (Total)= "153" Final Enrollment numbers achieved (India)="153"
Individual Participant Data (IPD) Sharing Statement
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Brief Summary
This is Randomized, Assessor-Blind, Multicentre, Parallel
Group, Two Arms, Clinical Study to Assess the Efficacy, Pharmacokinetics,
Pharmacodynamics, Immunogenicity and Safety of Rituximab (Test Product, Zydus)
in comparison with Rituximab (Reference Product, Roche/Genentech) in Patients
with Diffuse Large B Cell Lymphoma (DLBCL).