A Trial to Learn if Odronextamab Combined With Chemotherapy is Safe and Well-Tolerated and How Well it Works Compared to Rituximab Combined With Chemotherapy for Adult Participants With Follicular Lymphoma
- Conditions
- Follicular Lymphoma (FL)
- Interventions
- Drug: Prednisone/Prenisolone
- Registration Number
- NCT06097364
- Lead Sponsor
- Regeneron Pharmaceuticals
- Brief Summary
This study is researching an experimental drug called odronextamab, referred to as study drug. The study is focused on participants with previously untreated follicular lymphoma. Follicular lymphoma is a type of non-Hodgkin lymphoma or NHL. Participants with follicular lymphoma that has come back after treatment (called "relapsed") or did not respond to treatment (called "refractory") are eligible to take part only in Part 1A of the study.
This study is made up of 3 parts: Part 1A (non-randomized), Part 1B and Part 2 (randomized - controlled).
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 to be used in Part 2 of the study.
The aim of Part 2 of the study is to assess 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 for 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
* How much study drug is in the blood at different times
* Whether the body makes antibodies against the study drug (which could make the study drug less effective or could lead to side effects)
* The impact from the study drug on quality-of-life and ability to complete routine daily activities
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 733
-
Have diagnosis of cluster of differentiation 20 positive (CD20+) FL grade 1-3a, stage II bulky or stage III / IV
- For Part 1A: previously untreated participants who have Follicular Lymphoma International Prognostic Index (FLIPI)-1 score of 3 to 5, or R/R FL
- For Part 1B: previously untreated participants who have FLIPI-1 score of 3 to 5
- For Part 2: previously untreated participants who have FLIPI-1 score of 0 to 5
-
Have measurable disease on cross sectional imaging documented by diagnostic computed tomography [CT], or magnetic resonance imaging [MRI] imaging, as described in the protocol
-
Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
-
Adequate bone marrow and hepatic function.
Key
- Participants with central nervous system lymphoma or leptomeningeal lymphoma
- Participants with histological evidence of transformation to a high-grade or diffuse large B-cell lymphoma
- Participants with Waldenström macroglobulinemia (WM, lymphoplasmacytic lymphoma), grade 3b follicular lymphoma, chronic lymphocytic leukemia or small lymphocytic lymphoma
- Recent major surgery and history or organ transplantation
- A malignancy other than NHL unless the participant is adequately and definitively treated and any other significant active disease or medical condition that could interfere with the conduct of the study or put the participant at significant risk, as described in the protocol.
Note: Other protocol-defined Inclusion/Exclusion criteria apply
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Odronextamab + Chemotherapy Odronextamab Part 1 of the study includes ordonextamab dose escalation for participants with previously untreated FL and relapsed/refractory FL (Part 1A only) followed by a randomized exploration of 2 regimens of odronextamab (Odro) and cyclophosphamide, doxorubicin, vincristine, prednisone (CHOP) with the objective of dose optimization (Part 1B) in previously untreated patients with FL. Odronextamab + Chemotherapy Prednisone/Prenisolone Part 1 of the study includes ordonextamab dose escalation for participants with previously untreated FL and relapsed/refractory FL (Part 1A only) followed by a randomized exploration of 2 regimens of odronextamab (Odro) and cyclophosphamide, doxorubicin, vincristine, prednisone (CHOP) with the objective of dose optimization (Part 1B) in previously untreated patients with FL. Rituximab + Chemotherapy Prednisone/Prenisolone In Part 2 only, participants will be randomized 1:1:1 to receive rituximab (R) with chemotherapy (CHOP), followed by rituximab monotherapy maintenance. Odronextamab + Chemotherapy Cyclophosphamide Part 1 of the study includes ordonextamab dose escalation for participants with previously untreated FL and relapsed/refractory FL (Part 1A only) followed by a randomized exploration of 2 regimens of odronextamab (Odro) and cyclophosphamide, doxorubicin, vincristine, prednisone (CHOP) with the objective of dose optimization (Part 1B) in previously untreated patients with FL. Odronextamab + Chemotherapy Doxorubicin Part 1 of the study includes ordonextamab dose escalation for participants with previously untreated FL and relapsed/refractory FL (Part 1A only) followed by a randomized exploration of 2 regimens of odronextamab (Odro) and cyclophosphamide, doxorubicin, vincristine, prednisone (CHOP) with the objective of dose optimization (Part 1B) in previously untreated patients with FL. Rituximab + Chemotherapy Odronextamab In Part 2 only, participants will be randomized 1:1:1 to receive rituximab (R) with chemotherapy (CHOP), followed by rituximab monotherapy maintenance. Rituximab + Chemotherapy Rituximab In Part 2 only, participants will be randomized 1:1:1 to receive rituximab (R) with chemotherapy (CHOP), followed by rituximab monotherapy maintenance. Rituximab + Chemotherapy Cyclophosphamide In Part 2 only, participants will be randomized 1:1:1 to receive rituximab (R) with chemotherapy (CHOP), followed by rituximab monotherapy maintenance. Rituximab + Chemotherapy Doxorubicin In Part 2 only, participants will be randomized 1:1:1 to receive rituximab (R) with chemotherapy (CHOP), followed by rituximab monotherapy maintenance. Rituximab + Chemotherapy Vincristine In Part 2 only, participants will be randomized 1:1:1 to receive rituximab (R) with chemotherapy (CHOP), followed by rituximab monotherapy maintenance. Odronextamab + Chemotherapy + Maintenance Vincristine In Part 2, participants will be randomized 1:1:1 to receive odronextamab with chemotherapy \[CHOP, or cyclophosphamide, vincristine, and prednisone (CVP)\], followed by odronextamab monotherapy maintenance. Odronextamab + Chemotherapy + No maintenance Vincristine In Part 2, participants will be randomized 1:1:1 to receive odronextamab with chemotherapy (CHOP, or CVP) without maintenance. Odronextamab + Chemotherapy + No maintenance Odronextamab In Part 2, participants will be randomized 1:1:1 to receive odronextamab with chemotherapy (CHOP, or CVP) without maintenance. Odronextamab + Chemotherapy + Maintenance Odronextamab In Part 2, participants will be randomized 1:1:1 to receive odronextamab with chemotherapy \[CHOP, or cyclophosphamide, vincristine, and prednisone (CVP)\], followed by odronextamab monotherapy maintenance.
- Primary Outcome Measures
Name Time Method Incidence of dose limiting toxicities (DLTs) for odronextamab in combination with chemotherapy Up to 35 days Part 1, DLT period
Complete Response rate at 30 months (CR30) assessed by independent central review (ICR) Up to 30 months Part 2
Incidence of treatment-emergent adverse events (TEAEs) of odronextamab in combination with chemotherapy Up to 2 years Part 1, Treatment period
Severity of TEAEs of odronextamab in combination with chemotherapy Up to 2 years Part 1, Treatment period
- Secondary Outcome Measures
Name Time Method PFS as assessed by local investigator Up to 5 years Part 2
Incidence of neutralizing antibodies (NAb) to odronextamab Up to 30 months Part 1 and Part 2
Change in patient reported physical functioning scale scores on the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Cancer-30 (EORTC-QLQ-C30) Up to 5 years 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 global health status (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.
Best overall response (BOR) as assessed by the investigator Up to 30 months Part 1, end of Induction period and end of Maintenance period
Progression free survival (PFS) as assessed by ICR Up to 5 years Part 2
Change in patient reported health related quality of life (HRQoL) as measured by EORTC-QLQ-C30 Up to 5 years 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 in cancer disease as measured by EORTC-QLQ-C30 Up to 5 years 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.
Incidence of anti-odronextamab antibodies (ADAs) Up to 30 months Part 1 and Part 2
Overall Survival (OS) Up to 5 years Part 2
Change in patient-reported treatment side effects burden per Functional Assessment of Cancer Therapy-General Global Population Item 5 (FACT-G GP5) Up to 5 years 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).
Titers of ADAs to odronextamab Up to 30 months Part 1 and Part 2
CR30 as assessed by local investigator Up to 30 months Part 2
BOR as assessed by local investigator Up to 30 months Part 2
BOR as assessed by ICR Up to 30 months Part 2
Duration of response (DOR) assessed by ICR Up to 5 years Part 2
DOR as assessed by local investigator Up to 5 years Part 2
Incidence of TEAEs Up to 2 years Part 2
Change in treatment related symptoms as measured by EORTC-QLQ-C30 Up to 5 years 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 in treatment-related symptoms as measured by the FACT-LymS Up to 5 years Part 2 The FACT-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.
Odronextamab concentrations in serum when administered with chemotherapy Up to 30 months Part 1, Maintenance period and Part 2, Induction period
Odronextamab concentrations in serum when administered as monotherapy Up to 30 months Part 1 and Part 2, Maintenance period
Event-free survival (EFS) as assessed by ICR Up to 5 years Part 2
EFS as assessed by local investigator Up to 5 years Part 2
Change in Patient Global Impression of Severity (PGIS) Up to 5 years 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 to next anti-lymphoma treatment (TTNT) Up to 5 years Part 2
Severity of TEAEs Up to 2 years Part 2
Change in patient-reported general health status per EuroQol-5 Dimensions-5 Levels (EQ-5D-5L) Up to 5 years 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 patient-reported lymphoma disease as measured by the Lymphoma Subscale of the Functional Assessment of Cancer Treatment-Lymphoma (FACT-LymS) Up to 5 years 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 in Patient Global Impression of Change (PGIC) Up to 5 years 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 in score of the FACT-G GP5 item in the patient population Up to 5 years 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).
Trial Locations
- Locations (135)
Hospital Alemao Oswaldo Cruz
🇧🇷Sao Paulo, Brazil
Clinical Hospital of Medicine School at Sao Paulo University
🇧🇷Sao Paulo, Brazil
ASST Grande Ospedale Metropolitano Niguarda - Main Address
🇮🇹Milan, Italy
Boca Raton Clinical Research (BRCR) Global
🇺🇸Plantation, Florida, United States
Investigative Clinical Research of Indiana
🇺🇸Noblesville, Indiana, United States
University of Kentucky
🇺🇸Lexington, Kentucky, United States
Henry Ford Health System
🇺🇸Detroit, Michigan, United States
Cancer and Hematology Centers of Western Michigan
🇺🇸Grand Rapids, Michigan, United States
Clinical Research Alliance Inc
🇺🇸Westbury, New York, United States
Center for Oncology and Blood Disorders
🇺🇸Houston, Texas, United States
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