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A Study to Compare How Well Odronextamab Combined With Chemotherapy Works and How Safe it is Against Rituximab Combined With Chemotherapy, in Patients With Previously Untreated Diffuse Large B-cell Lymphoma (OLYMPIA-3)

Primary Purpose

Diffuse Large B-cell Lymphoma (DLBCL)

Status
Recruiting
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
Odronextamab
Rituximab
Cyclophosphamide
Doxorubicin
Vincristine
Prednisone/Prednisolone
Sponsored by
Regeneron Pharmaceuticals
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Diffuse Large B-cell Lymphoma (DLBCL) focused on measuring Non-Hodgkin lymphomas (NHL), B-cell non-Hodgkin lymphomas (B-NHL), Diffuse Large B-cell Lymphoma, Odronextamab, Anti-CD20 × anti-CD3 bispecific antibody

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

KEY Inclusion Criteria: Previously untreated participants for lymphoma with documented cluster of differentiation 20+ (CD20+) DLBCL, as described in the protocol OR relapsed or refractory DLBCL (Part 1A only) Measurable disease with at least one nodal lesion or at least one extranodal lesion, as described in the protocol Eastern Cooperative Oncology Group (ECOG) performance status ≤2 Life expectancy ≥ 12 months International Prognostic Index (IPI) of 3 to 5 (part 1 only) and ≥2 (part 2) for untreated DLBCL only; Adequate hematologic and organ function, as defined in the protocol. KEY Exclusion Criteria: Primary central nervous system (CNS) lymphoma or known involvement by non-primary CNS NHL and history or current relevant CNS pathology Another active malignancy, significant active disease or medical condition, as described in the protocol Peripheral neuropathy Grade ≥3 Treatment with any systemic anti-lymphoma therapy Any investigational therapy within 28 days or 5 half-lives of the drug, whichever is shorter, prior to the start of study treatment Recent major surgery, prior organ transplantation, or standard radiotherapy, as described in the protocol Allergy/hypersensitivity to study drugs, as described in the protocol Infections such as any active infection (bacterial, viral, fungal, mycobacterial, parasitic or other), active Coronavirus disease (COVID-19) infection, uncontrolled infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV), or hepatitis C virus (HCV), Cytomegalovirus (CMV) infection, as described in the protocol. Note: Other protocol-defined Inclusion/ Exclusion criteria apply

Sites / Locations

  • Clinical Research Alliance IncRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Odronextamab + CHOP

Rituximab + CHOP

Arm Description

Part 1, includes dose escalation (Part 1A), and randomized exploration of 2 regimens of odronextamab -cyclophosphamide, doxorubicin, vincristine, prednisone (O-CHOP) dose optimization, (Part 1B).

Part 2 is the randomized controlled portion, participants will receive either O-CHOP or R-CHOP.

Outcomes

Primary Outcome Measures

Incidence of dose limiting toxicities (DLTs)
Part 1
Incidence of treatment emergent adverse events (TEAEs)
Part 1
Severity of TEAEs
Part 1
Progression free survival (PFS), assessed by independent central review (ICR)
Part 2

Secondary Outcome Measures

Event-free survival (EFS) assessed by ICR
Part 2
Complete response (CR) assessed by ICR
Part 2
Overall survival (OS)
Part 2
Best Overall response (BOR) as assessed by local investigators
Part 1 and Part 2
CR as assessed by local investigators
Part 1 and Part 2
Duration of response (DOR) as assessed by local investigators
Part 1 and Part 2
Odronextamab concentrations in serum when administered with CHOP
Part 1 and Part 2
Incidence of anti-drug antibodies (ADA) to odronextamab when administered with CHOP
Part 1 and Part 2
Titer of ADA to odronextamab when administered with CHOP
Part 1 and Part 2
Incidence of neutralizing antibodies (NAb) to odronextamab when administered with CHOP
Part 1 and Part 2
PFS assessed by local investigator review
Part 2
EFS assessed by local investigator review
Part 2
BOR assessed by ICR
Part 2
DOR assessed by ICR
Part 2
Incidence of TEAEs
Part 2
Severity of TEAEs
Part 2
Measurable Residual Disease (MRD) status
Part 2
Duration of MRD-negativity
Part 2
Change in physical functioning as measured by EORTC QLQ C30
Part 2 The EORTC QLQ-C30 includes 5 functional scales (physical, role, cognitive, emotional and social functioning), 3 symptom scales (fatigue, pain and nausea/vomiting), a GHS/QoL scale, and six single items (constipation, diarrhea, insomnia, shortness of breath, appetite loss and financial difficulties). For the functioning scales and global health status / QoL, scores range from 1 = "very poor" to 7 = "excellent" with higher scores indicate better functioning; for the symptom scales, scores range from 1 = "not at all" to 4 = "very much" higher scores indicate higher symptom burden.
Change from baseline of patient reported outcomes, as measured by European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire (EORTC QLQ-C) 30
Part 2 The EORTC QLQ-C30 includes 5 functional scales (physical, role, cognitive, emotional and social functioning), 3 symptom scales (fatigue, pain and nausea/vomiting), a GHS/QoL scale, and six single items (constipation, diarrhea, insomnia, shortness of breath, appetite loss and financial difficulties). For the functioning scales and global health status / QoL, scores range from 1 = "very poor" to 7 = "excellent" with higher scores indicate better functioning; for the symptom scales, scores range from 1 = "not at all" to 4 = "very much" higher scores indicate higher symptom burden.
Change from baseline of patient reported outcomes, as measured by Functional Assessment of Cancer Therapy - Lymphoma Subscale (FACT-LymS)
Part 2 The FACT-Lym lymphoma subscale (LymS) includes 15 items to assess NHL-related symptoms and concerns. All questions are answered on a 5-point scale ranging from "not at all" (0) to "very much" (4). Higher scores are associated with a worse quality of life.
Change from baseline of patient reported outcomes, as measured by Patient Global Impression of Severity (PGIS)
Part 2 The PGIS includes a single-item to assess how a patient perceives the overall severity of cancer symptoms over the past 7 days. Patients will choose the response that best describes the severity of their overall cancer symptoms with options on a 5-point scale ranging from 1 (No symptoms) to 4 (Very Severe).
Change from baseline of patient reported outcomes, as measured by Patient Global Impression of Change (PGIC)
Part 2 The PGIC item includes a single-item to assess how a patient perceives their overall change in health status since the start of study treatment. Patients will choose from response options on a 7-point scale ranging from 1 (Much Better) to 7 (Much worse); 1- Much Better, 2-Moderately Better, 3-A Little Better, 4-About the Same, 5-A Little Worse, 6-Moderately Worse, 7-Much Worse.
Change from baseline of patient reported outcomes, as measured by EuroQol-5 Dimension-5 Level Scale (EQ-5D-5L)
Part 2 The EQ-5D-5L consists of the EQ-5D descriptive system and the EQ visual analogue scale (EQ VAS). The EQ-5D-5L descriptive system comprises the following 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 levels: "no problems", "slight problems", "moderate problems", "severe problems" and "extreme problems". The EQ VAS records the participant's self-rated health on a vertical visual analogue scale where the endpoints are labeled "Best imaginable health state" and "Worst imaginable health state".
Change in score of the Functional Assessment of Cancer Therapy-General (FACT-G ) GP5 item
Part 2 A single item (GP5) of the validated FACT-G questionnaire will be used to assess from the participant perspective the overall impact of treatment side-effect. The question item is on a 5-point scale ranging from "not at all" (0) to "very much" (4).

Full Information

First Posted
October 13, 2023
Last Updated
October 13, 2023
Sponsor
Regeneron Pharmaceuticals
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1. Study Identification

Unique Protocol Identification Number
NCT06091865
Brief Title
A Study to Compare How Well Odronextamab Combined With Chemotherapy Works and How Safe it is Against Rituximab Combined With Chemotherapy, in Patients With Previously Untreated Diffuse Large B-cell Lymphoma
Acronym
OLYMPIA-3
Official Title
A Phase 3, Open Label, Randomized Study Comparing the Efficacy and Safety of Odronextamab (REGN1979), an Anti-CD20 × Anti-CD3 Bispecific Antibody, in Combination With CHOP (O-CHOP) Versus Rituximab in Combination With CHOP (R-CHOP) in Previously Untreated Participants With Diffuse Large B-cell Lymphoma (DLBCL) (OLYMPIA-3)
Study Type
Interventional

2. Study Status

Record Verification Date
September 2023
Overall Recruitment Status
Recruiting
Study Start Date
October 18, 2023 (Anticipated)
Primary Completion Date
August 11, 2028 (Anticipated)
Study Completion Date
August 11, 2028 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Regeneron Pharmaceuticals

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This study is researching an experimental drug called odronextamab, referred to as study drug, when used in combination with chemotherapy. The study is focused on patients with diffuse large B-cell lymphoma (DLBCL) that have not been treated before (called "previously untreated"), have come back after treatment (called "relapsed"), or have not responded to treatment (called "refractory"). This study will be made up of Part 1a, Part 1b, and Part 2.The aim of Part 1a and Part 1b of the study is to see how safe and tolerable the study drug in combination with chemotherapy is and to determine the dose and schedule of the study drug to be combined with chemotherapy in Part 2 of the study. The aim of Part 2 of the study is to see how effective the combination of the study drug with chemotherapy is in comparison with the combination of rituximab and chemotherapy, the current standard of care treatment approved for Non-Hodgkin's lymphoma (NHL). Standard of care means the usual medication expected and used when receiving treatment for a condition. The study is looking at several other research questions, including: What side effects may happen from taking the study drug when combined with chemotherapy How much study drug is in your blood at different times Whether the body makes antibodies against the study drug (which could make the drug less effective or could lead to side effects) The impact from the study drug on your quality of life and ability to complete routine daily activities

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Diffuse Large B-cell Lymphoma (DLBCL)
Keywords
Non-Hodgkin lymphomas (NHL), B-cell non-Hodgkin lymphomas (B-NHL), Diffuse Large B-cell Lymphoma, Odronextamab, Anti-CD20 × anti-CD3 bispecific antibody

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
904 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Odronextamab + CHOP
Arm Type
Experimental
Arm Description
Part 1, includes dose escalation (Part 1A), and randomized exploration of 2 regimens of odronextamab -cyclophosphamide, doxorubicin, vincristine, prednisone (O-CHOP) dose optimization, (Part 1B).
Arm Title
Rituximab + CHOP
Arm Type
Active Comparator
Arm Description
Part 2 is the randomized controlled portion, participants will receive either O-CHOP or R-CHOP.
Intervention Type
Drug
Intervention Name(s)
Odronextamab
Other Intervention Name(s)
REGN1979
Intervention Description
Odronextamab will be administered by intravenous (IV) infusion
Intervention Type
Drug
Intervention Name(s)
Rituximab
Other Intervention Name(s)
Rituxan
Intervention Description
Rituximab will be administered IV, or subcutaneously (SC)
Intervention Type
Drug
Intervention Name(s)
Cyclophosphamide
Other Intervention Name(s)
Cytoxan
Intervention Description
Cyclophosphamide will be administered IV as part of chemotherapy
Intervention Type
Drug
Intervention Name(s)
Doxorubicin
Other Intervention Name(s)
Adriamycin
Intervention Description
Doxorubicin will be administered IV as part of chemotherapy
Intervention Type
Drug
Intervention Name(s)
Vincristine
Other Intervention Name(s)
Oncovin
Intervention Description
Vincristine will be administered IV as part of chemotherapy
Intervention Type
Drug
Intervention Name(s)
Prednisone/Prednisolone
Other Intervention Name(s)
Deltasone/Omnipred
Intervention Description
Prednisone or prednisolone will be administered orally (PO) as part of chemotherapy
Primary Outcome Measure Information:
Title
Incidence of dose limiting toxicities (DLTs)
Description
Part 1
Time Frame
Up to 35 days
Title
Incidence of treatment emergent adverse events (TEAEs)
Description
Part 1
Time Frame
Up to 2 years
Title
Severity of TEAEs
Description
Part 1
Time Frame
Up to 2 years
Title
Progression free survival (PFS), assessed by independent central review (ICR)
Description
Part 2
Time Frame
Up to 5 years
Secondary Outcome Measure Information:
Title
Event-free survival (EFS) assessed by ICR
Description
Part 2
Time Frame
Up to 5 years
Title
Complete response (CR) assessed by ICR
Description
Part 2
Time Frame
Up to 22 weeks
Title
Overall survival (OS)
Description
Part 2
Time Frame
Up to 5 years
Title
Best Overall response (BOR) as assessed by local investigators
Description
Part 1 and Part 2
Time Frame
Up to 22 weeks
Title
CR as assessed by local investigators
Description
Part 1 and Part 2
Time Frame
Up to 22 weeks
Title
Duration of response (DOR) as assessed by local investigators
Description
Part 1 and Part 2
Time Frame
Up to 5 years
Title
Odronextamab concentrations in serum when administered with CHOP
Description
Part 1 and Part 2
Time Frame
Up to 22 weeks
Title
Incidence of anti-drug antibodies (ADA) to odronextamab when administered with CHOP
Description
Part 1 and Part 2
Time Frame
Up to 22 weeks
Title
Titer of ADA to odronextamab when administered with CHOP
Description
Part 1 and Part 2
Time Frame
Up to 22 weeks
Title
Incidence of neutralizing antibodies (NAb) to odronextamab when administered with CHOP
Description
Part 1 and Part 2
Time Frame
Up to 22 weeks
Title
PFS assessed by local investigator review
Description
Part 2
Time Frame
Up to 5 years
Title
EFS assessed by local investigator review
Description
Part 2
Time Frame
Up to 5 years
Title
BOR assessed by ICR
Description
Part 2
Time Frame
Up to 22 weeks
Title
DOR assessed by ICR
Description
Part 2
Time Frame
Up to 5 years
Title
Incidence of TEAEs
Description
Part 2
Time Frame
Up to 2 years
Title
Severity of TEAEs
Description
Part 2
Time Frame
Up to 2 years
Title
Measurable Residual Disease (MRD) status
Description
Part 2
Time Frame
Up to 22 weeks
Title
Duration of MRD-negativity
Description
Part 2
Time Frame
Up to 5 years
Title
Change in physical functioning as measured by EORTC QLQ C30
Description
Part 2 The EORTC QLQ-C30 includes 5 functional scales (physical, role, cognitive, emotional and social functioning), 3 symptom scales (fatigue, pain and nausea/vomiting), a GHS/QoL scale, and six single items (constipation, diarrhea, insomnia, shortness of breath, appetite loss and financial difficulties). For the functioning scales and global health status / QoL, scores range from 1 = "very poor" to 7 = "excellent" with higher scores indicate better functioning; for the symptom scales, scores range from 1 = "not at all" to 4 = "very much" higher scores indicate higher symptom burden.
Time Frame
Up to 5 years
Title
Change from baseline of patient reported outcomes, as measured by European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire (EORTC QLQ-C) 30
Description
Part 2 The EORTC QLQ-C30 includes 5 functional scales (physical, role, cognitive, emotional and social functioning), 3 symptom scales (fatigue, pain and nausea/vomiting), a GHS/QoL scale, and six single items (constipation, diarrhea, insomnia, shortness of breath, appetite loss and financial difficulties). For the functioning scales and global health status / QoL, scores range from 1 = "very poor" to 7 = "excellent" with higher scores indicate better functioning; for the symptom scales, scores range from 1 = "not at all" to 4 = "very much" higher scores indicate higher symptom burden.
Time Frame
Up to 5 years
Title
Change from baseline of patient reported outcomes, as measured by Functional Assessment of Cancer Therapy - Lymphoma Subscale (FACT-LymS)
Description
Part 2 The FACT-Lym lymphoma subscale (LymS) includes 15 items to assess NHL-related symptoms and concerns. All questions are answered on a 5-point scale ranging from "not at all" (0) to "very much" (4). Higher scores are associated with a worse quality of life.
Time Frame
Up to 5 years
Title
Change from baseline of patient reported outcomes, as measured by Patient Global Impression of Severity (PGIS)
Description
Part 2 The PGIS includes a single-item to assess how a patient perceives the overall severity of cancer symptoms over the past 7 days. Patients will choose the response that best describes the severity of their overall cancer symptoms with options on a 5-point scale ranging from 1 (No symptoms) to 4 (Very Severe).
Time Frame
Up to 5 years
Title
Change from baseline of patient reported outcomes, as measured by Patient Global Impression of Change (PGIC)
Description
Part 2 The PGIC item includes a single-item to assess how a patient perceives their overall change in health status since the start of study treatment. Patients will choose from response options on a 7-point scale ranging from 1 (Much Better) to 7 (Much worse); 1- Much Better, 2-Moderately Better, 3-A Little Better, 4-About the Same, 5-A Little Worse, 6-Moderately Worse, 7-Much Worse.
Time Frame
Up to 5 years
Title
Change from baseline of patient reported outcomes, as measured by EuroQol-5 Dimension-5 Level Scale (EQ-5D-5L)
Description
Part 2 The EQ-5D-5L consists of the EQ-5D descriptive system and the EQ visual analogue scale (EQ VAS). The EQ-5D-5L descriptive system comprises the following 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 levels: "no problems", "slight problems", "moderate problems", "severe problems" and "extreme problems". The EQ VAS records the participant's self-rated health on a vertical visual analogue scale where the endpoints are labeled "Best imaginable health state" and "Worst imaginable health state".
Time Frame
Up to 5 years
Title
Change in score of the Functional Assessment of Cancer Therapy-General (FACT-G ) GP5 item
Description
Part 2 A single item (GP5) of the validated FACT-G questionnaire will be used to assess from the participant perspective the overall impact of treatment side-effect. The question item is on a 5-point scale ranging from "not at all" (0) to "very much" (4).
Time Frame
Up to 5 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
KEY Inclusion Criteria: Previously untreated participants for lymphoma with documented cluster of differentiation 20+ (CD20+) DLBCL, as described in the protocol OR relapsed or refractory DLBCL (Part 1A only) Measurable disease with at least one nodal lesion or at least one extranodal lesion, as described in the protocol Eastern Cooperative Oncology Group (ECOG) performance status ≤2 Life expectancy ≥ 12 months International Prognostic Index (IPI) of 3 to 5 (part 1 only) and ≥2 (part 2) for untreated DLBCL only; Adequate hematologic and organ function, as defined in the protocol. KEY Exclusion Criteria: Primary central nervous system (CNS) lymphoma or known involvement by non-primary CNS NHL and history or current relevant CNS pathology Another active malignancy, significant active disease or medical condition, as described in the protocol Peripheral neuropathy Grade ≥3 Treatment with any systemic anti-lymphoma therapy Any investigational therapy within 28 days or 5 half-lives of the drug, whichever is shorter, prior to the start of study treatment Recent major surgery, prior organ transplantation, or standard radiotherapy, as described in the protocol Allergy/hypersensitivity to study drugs, as described in the protocol Infections such as any active infection (bacterial, viral, fungal, mycobacterial, parasitic or other), active Coronavirus disease (COVID-19) infection, uncontrolled infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV), or hepatitis C virus (HCV), Cytomegalovirus (CMV) infection, as described in the protocol. Note: Other protocol-defined Inclusion/ Exclusion criteria apply
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Clinical Trials Administrator
Phone
844-734-6643
Email
clinicaltrials@regeneron.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clinical Trial Management
Organizational Affiliation
Regeneron Pharmaceuticals
Official's Role
Study Director
Facility Information:
Facility Name
Clinical Research Alliance Inc
City
Westbury
State/Province
New York
ZIP/Postal Code
11590
Country
United States
Individual Site Status
Recruiting

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
All Individual Patient Data (IPD) that underlie publicly available results will be considered for sharing.
IPD Sharing Time Frame
When Regeneron has received marketing authorization from major health authorities (e.g., FDA, European Medicines Agency (EMA), Pharmaceuticals and Medical Devices Agency (PMDA), etc.) for the product and indication, has made results publicly available (e.g., scientific publication, scientific conference, clinical trial registry), has the legal authority to share the data, and has ensured the ability to protect participant privacy.
IPD Sharing Access Criteria
Qualified researchers can submit a proposal for access to individual patient or aggregate level data from a Regeneron-sponsored clinical trial through Vivli. Regeneron's Independent Research Request Evaluation Criteria can be found at: https://www.regeneron.com/sites/default/files/Regeneron-External-Data-Sharing-Policy-and-Independent-Research-Request-Evaluation-Criteria.pdf
IPD Sharing URL
https://vivli.org/

Learn more about this trial

A Study to Compare How Well Odronextamab Combined With Chemotherapy Works and How Safe it is Against Rituximab Combined With Chemotherapy, in Patients With Previously Untreated Diffuse Large B-cell Lymphoma

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