This trial is randomized, double-blinded study to evaluate the safety, efficacy and immunogenicity of ABP 798 compared with Rituximab in patients with CD20 Positive B-Cell Non-Hodgkin Lymphoma

• Register: CTRI
• Last refreshed on: 24 November 2021
• Main ID: CTRI/2017/12/010935
• Date of registration: 21-12-2017
• Prospective Registration: Yes
• Primary sponsor: Amgen Inc
• Public title: This trial is randomized, double-blinded study to evaluate the safety, efficacy and immunogenicity of ABP 798 compared with Rituximab in patients with CD20 Positive B-Cell Non-Hodgkin Lymphoma
• Scientific title: A Randomized, Double-blind Study Evaluating the Efficacy, Safety and Immunogenicity of ABP 798 Compared with Rituximab in Subjects with CD20 Positive B-cell Non-Hodgkin Lymphoma (NHL)
• Date of first enrolment: 03-01-2018
• Target sample size: 250
• Recruitment status: Completed
• URL: http://www.ctri.nic.in/Clinicaltrials/pmaindet2.php?trialid=2184
• Study type: Interventional
• Study design: Randomized, Parallel Group, Active Controlled Trial; Method of generating randomization sequence:Computer generated randomization Method of allocation concealment:Centralized Blinding and masking:Participant, Investigator, Outcome Assessor and Date-entry Operator Blinded
• Phase: Phase 3

Countries of recruitment

Argentina, Australia, Azerbaijan, Bulgaria, Canada, Colombia, Czech Republic, France, Georgia, Germany, Greece, Hungary, India, Israel, Italy, Japan, Mexico, Poland, Republic of Korea, Romania, Russian Federation, Spain, Ukraine, United States of America

Contacts

• Name: Dr Aparna Parikh
• Affiliation: Pharmaceutical Research Associates India Pvt. Ltd

• Name: Jigar Lakhani
• Affiliation: Pharmaceutical Research Associates India Pvt. Ltd

Key inclusion & exclusion criteria

Inclusion criteria: 1.Histologically confirmed (by lymph node or extranodal region biopsy), Grade 1, 2, or 3a follicular B-cell NHL expressing CD20 within 12 months before randomization

2. Stage 2, 3, or 4 (per Cotswoldâ??s Modification of Ann Arbor Staging System

3. Low tumor burden based on the GELF Criteria

a.largest nodal or extranodal mass <= 7 cm

b. no more than 3 nodal sites with diameter > 3 cm

c.no splenomegaly > 16 cm by CT scan and no symptomatic splenomegaly

d. no significant pleural or peritoneal serous effusions by CT

e.lactate dehydrogenase <= upper limit of normal (ULN)m before any study specific procedures

f. no B symptoms (night sweats, fever [temperature > 38°C], weight loss > 10% in the previous 6 months)

4. Eastern Cooperative Oncology Group (ECOG) performance status score 0 or 1 with measurable disease (per International Working Group)

a. subjects must have a baseline scan (computed tomography [CT]) of the neck (if palpable lymph node > 1.0 cm), chest, abdomen, and pelvis to assess disease burden within 6 weeks before randomization

b. subjects must have had a baseline bone marrow biopsy within 12 months before randomization. Previously confirmed positive bone marrow involvement does not need to be repeated for purposes of screening.

5. Blood counts:

a.absolute neutrophil count (ANC) >= 1.5 x 109/L (1,500/μL)

b. lymphocytes < 1.5 x the ULN

c.platelets >= 100 x 109/L (100,000/μL)

d. hemoglobin >= 10.0 g/dL

6. Adequate hepatic function as defined by:

a.total bilirubin < 1.5 x the ULN

b. aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 2 x ULN

c. Subjects with an elevated unconjugated bilirubin will be eligible if hepatic enzymes and function are otherwise within normal limits and there is no evidence of hemolysis.

7. Adequate renal function as defined by creatinine < 1.5 x ULN or estimated creatinine clearance >= 50 mL/min calculated by the Cockcroft-Gault method

8. Subjects must sign an IRB-approved informed consent form before any study specific procedures.


Exclusion criteria: 1.Diffuse large cell component and/or Grade 3b follicular NHL

2. History or known presence of central nervous system metastases

3. Palliative radiotherapy within 3 months before randomization

4. Malignancy other than NHL within 5 years (except treated in-situ cervical cancer, or

squamous or basal cell carcinoma of the skin)

5. Major surgical procedure within 4 weeks before randomization or planned major surgical

procedure during the treatment phase

6. Any of the following in the 6 months before randomization:

• clinically significant cardiovascular disease (including myocardial infarction, unstable

angina, symptomatic congestive heart failure [New York Heart Association

>= Class III], serious uncontrolled cardiac arrhythmia); peripheral vascular disease,

cerebrovascular accident, or transient ischemic attack

7. Medically uncontrolled hypertension or systolic blood pressure > 160 mmHg or diastolic

blood pressure > 100 mmHg

8. Known active or history of active tuberculosis (TB)

9. Positive for hepatitis B surface antigen, hepatitis B core antibody, or hepatitis C virus

antibody at screening

10. Known to be human immunodeficiency virus positive

11. Recent infection requiring a course of systemic anti-infective agents that was completed

<= 7 days before randomization (with the exception of uncomplicated urinary tract

infection)

12. Other investigational procedures that can impact the study data, results, or patient

safety while participating in this study are excluded; participation in observational

studies is allowed.

13. Subject is currently enrolled in or has not yet completed at least 30 days or 5 half-lives

(whichever is longer) since ending other investigational device or drug study(s), including

vaccines, or subject is receiving other investigational agent(s)

14. Previous use of either commercially available or investigational chemotherapy, biological,

or immunological therapy for NHL (including rituximab or biosimilar rituximab, or other

anti-CD20 treatments)

15. Systemic corticosteroid use within 3 months before randomization (inhaled are

allowable)

16. Live vaccines within 28 days prior to the first dose of IP

17. History of neurologic symptoms suggestive of central nervous system demyelinating

Disease

18. Woman of childbearing potential who is pregnant or is breastfeeding

19. Woman of childbearing potential who does not consent to use highly effective methods of

birth control (eg, true abstinence, sterilization, birth control pills, Depo Provera injections,

or contraceptive implants) during treatment and for an additional 12 months after the last

administration of the protocol specified-treatment

20. Man with a partner of childbearing potential who does not consent to use highly effective

methods of birth control (eg, true abstinence, vasectomy, or a condom in combination

with hormonal birth control or barrier methods used by the woman) during treatment and

for an additional 12 months after the last administration of the protocol specified

treatment

21. Subject has known sensitivity to any of the products to be administered during the study,

including mammalian cell derived drug products

22. Subject p

Age minimum:
Age maximum:
Gender:

Health Condition(s) or Problem(s) studied

Health Condition 1: C823- Follicular lymphoma grade IIIa

Intervention(s)

Intervention1: ABP 798: ABP 798 is a genetically engineered chimeric murine/human monoclonal IgG1 kappa antibody directed against the CD20 antigen with an identical amino acid sequence to that of rituximab.
Control Intervention1: Rituximab: Rituximab (Rituxan®) is a genetically engineered chimeric murine/human monoclonal IgG1 kappa antibody directed against the CD20 antigen.

Primary Outcome(s)

Risk difference (RD) of overall response rate (ORR) of efficacy of ABP 798 compared with rituximab.Timepoint: week 28

Secondary Outcome(s)

Geometric mean ratio (GMR) of test (ABP 798)-to-reference (rituximab)Timepoint: Predose and after end of infusion at week 12

On study overall survivalTimepoint: Up to Week 28

On study progression-free survivalTimepoint: Up to Week 28

Subject incidence of treatment-emergent AEs and serious adverse events. Clinical significant changes in laboratory values and vital signs will be reported as AEsTimepoint: Up to Week 28

Risk difference (RD) of overall response rate (ORR)of efficacy of ABP 798 compared with rituximab.Timepoint: Week 12

Percent of subjects with complete depletion of CD19 cell count and total Immunoglobin G (IgG) and IgM antibody levelsTimepoint: Baseline to study day 8

Serum concentrations at predose and immediately after the end of infusionTimepoint: week 12

Incidence of anti-drug antibodiesTimepoint: Up to Week 28

Secondary ID(s)

AMGEN798-20130109 Protocol V 5.0 dated 17 Jul 2017

2013-005542-11

Source(s) of Monetary Support

Amgen Inc One Amgen Center Drive Thousand Oaks, CA USA 91320

Secondary Sponsor(s)

Pharmaceutical Research Associates India Pvt

Ethics review

Status: Approved
Approval date: 03/02/2018
Contact:

Sri Venkateshwara Hospital Ethics Committee

Status: Approved
Approval date: 07/02/2018
Contact:

Institutional Ethics Committee-Government Stanley Medical College and Hospital

Status: Approved
Approval date: 15/02/2018
Contact:

Ethics Committee -Unique Hospital

Status: Approved
Approval date: 26/02/2018
Contact:

The Ethics Committee Care Institute of Medical Sciences

Status: Approved
Approval date: 27/02/2018
Contact:

Shatabdi Hospital Ethics Committee

Status: Approved
Approval date: 13/03/2018
Contact:

Institutional Ethics Committee-City Cancer Centre

Status: Approved
Approval date: 21/03/2018
Contact:

Manipal University Ethics Committee

Status: Approved
Approval date: 26/03/2018
Contact:

Poona Medical Research Foundation-Institutional Ethics Committee

Status: Approved
Approval date: 07/04/2018
Contact:

Manavata Clinical Research Institute,Ethics Committee

Status: Approved
Approval date: 09/04/2018
Contact:

Ethics Committee- S.P Medical College & A.G Hospitals

Status: Approved
Approval date: 13/04/2018
Contact:

Institutional Ethics Committee for Human Research

Status: Approved
Approval date: 24/04/2018
Contact:

Meenakshi Mission Hospital And Research Centre â??Institutional Ethics Committee

Status: Approved
Approval date: 28/05/2018
Contact:

Ethics Committee- Sir Ganga Ram Hospital

Results

• Date Completed: 11/06/2019