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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

Phase 3
Recruiting
Conditions
Follicular Lymphoma (FL)
Interventions
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
Inclusion Criteria
  1. Have diagnosis of cluster of differentiation 20 positive (CD20+) FL grade 1-3a, stage II bulky or stage III / IV

    1. For Part 1A: previously untreated participants who have Follicular Lymphoma International Prognostic Index (FLIPI)-1 score of 3 to 5, or R/R FL
    2. For Part 1B: previously untreated participants who have FLIPI-1 score of 3 to 5
    3. For Part 2: previously untreated participants who have FLIPI-1 score of 0 to 5
  2. Have measurable disease on cross sectional imaging documented by diagnostic computed tomography [CT], or magnetic resonance imaging [MRI] imaging, as described in the protocol

  3. Eastern Cooperative Oncology Group (ECOG) performance status of 0-2

  4. Adequate bone marrow and hepatic function.

Key

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Exclusion Criteria
  1. Participants with central nervous system lymphoma or leptomeningeal lymphoma
  2. Participants with histological evidence of transformation to a high-grade or diffuse large B-cell lymphoma
  3. Participants with Waldenström macroglobulinemia (WM, lymphoplasmacytic lymphoma), grade 3b follicular lymphoma, chronic lymphocytic leukemia or small lymphocytic lymphoma
  4. Recent major surgery and history or organ transplantation
  5. 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

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Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Odronextamab + ChemotherapyOdronextamabPart 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 + ChemotherapyPrednisone/PrenisolonePart 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 + ChemotherapyPrednisone/PrenisoloneIn Part 2 only, participants will be randomized 1:1:1 to receive rituximab (R) with chemotherapy (CHOP), followed by rituximab monotherapy maintenance.
Odronextamab + ChemotherapyCyclophosphamidePart 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 + ChemotherapyDoxorubicinPart 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 + ChemotherapyOdronextamabIn Part 2 only, participants will be randomized 1:1:1 to receive rituximab (R) with chemotherapy (CHOP), followed by rituximab monotherapy maintenance.
Rituximab + ChemotherapyRituximabIn Part 2 only, participants will be randomized 1:1:1 to receive rituximab (R) with chemotherapy (CHOP), followed by rituximab monotherapy maintenance.
Rituximab + ChemotherapyCyclophosphamideIn Part 2 only, participants will be randomized 1:1:1 to receive rituximab (R) with chemotherapy (CHOP), followed by rituximab monotherapy maintenance.
Rituximab + ChemotherapyDoxorubicinIn Part 2 only, participants will be randomized 1:1:1 to receive rituximab (R) with chemotherapy (CHOP), followed by rituximab monotherapy maintenance.
Rituximab + ChemotherapyVincristineIn Part 2 only, participants will be randomized 1:1:1 to receive rituximab (R) with chemotherapy (CHOP), followed by rituximab monotherapy maintenance.
Odronextamab + Chemotherapy + MaintenanceVincristineIn 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 maintenanceVincristineIn Part 2, participants will be randomized 1:1:1 to receive odronextamab with chemotherapy (CHOP, or CVP) without maintenance.
Odronextamab + Chemotherapy + No maintenanceOdronextamabIn Part 2, participants will be randomized 1:1:1 to receive odronextamab with chemotherapy (CHOP, or CVP) without maintenance.
Odronextamab + Chemotherapy + MaintenanceOdronextamabIn 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
NameTimeMethod
Incidence of dose limiting toxicities (DLTs) for odronextamab in combination with chemotherapyUp 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 chemotherapyUp to 2 years

Part 1, Treatment period

Severity of TEAEs of odronextamab in combination with chemotherapyUp to 2 years

Part 1, Treatment period

Secondary Outcome Measures
NameTimeMethod
PFS as assessed by local investigatorUp to 5 years

Part 2

Incidence of neutralizing antibodies (NAb) to odronextamabUp 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 investigatorUp to 30 months

Part 1, end of Induction period and end of Maintenance period

Progression free survival (PFS) as assessed by ICRUp to 5 years

Part 2

Change in patient reported health related quality of life (HRQoL) as measured by EORTC-QLQ-C30Up 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-C30Up 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

Odronextamab concentrations in serum when administered as monotherapyUp to 30 months

Part 1 and Part 2, Maintenance period

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).

Event-free survival (EFS) as assessed by ICRUp to 5 years

Part 2

Titers of ADAs to odronextamabUp to 30 months

Part 1 and Part 2

CR30 as assessed by local investigatorUp to 30 months

Part 2

BOR as assessed by local investigatorUp to 30 months

Part 2

BOR as assessed by ICRUp to 30 months

Part 2

Duration of response (DOR) assessed by ICRUp to 5 years

Part 2

DOR as assessed by local investigatorUp to 5 years

Part 2

Incidence of TEAEsUp to 2 years

Part 2

Change in treatment related symptoms as measured by EORTC-QLQ-C30Up 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-LymSUp 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.

EFS as assessed by local investigatorUp to 5 years

Part 2

Odronextamab concentrations in serum when administered with chemotherapyUp to 30 months

Part 1, Maintenance period and Part 2, Induction period

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 TEAEsUp 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 populationUp 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 (73)

The Hillingdon Hospitals NHS Foundation Trust

🇬🇧

Uxbridge, London, United Kingdom

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

Community Cancer Trials of Utah

🇺🇸

Ogden, Utah, United States

Prohealth Care Inc

🇺🇸

Waukesha, Wisconsin, United States

Liverpool Hospital

🇦🇺

Liverpool, New South Wales, Australia

Calvary Mater Newcastle

🇦🇺

Waratah, New South Wales, Australia

Pindara Private Hospital

🇦🇺

Benowa, Queensland, Australia

Verenigde Ziekenhuizen van Waas en Durme

🇧🇪

Sint Niklaas, Oost Vlaanderen, Belgium

Universitair Ziekenhuis (UZ) Gent/ Ghent University Hospital

🇧🇪

Gent, Oost-Vlaanderen, Belgium

AZ Groeninge

🇧🇪

Kortrijk, West Flanders, Belgium

Institut Jules Bordet

🇧🇪

Brussels, Belgium

Centre Hospitalier Regional de la Citadelle

🇧🇪

Liege, Belgium

Hospital Clinico Universidad de Los Andes

🇨🇱

Santiago, Las Condes, Chile

Pontificia Universidad Catolica de Chile

🇨🇱

Santiago, Region Metropolitana, Chile

Inmunocel

🇨🇱

Santiago, Region Metropolitana, Chile

Hadassah Medical Center

🇮🇱

Jerusalem, Israel

Rabin Medical Center

🇮🇱

Petah Tikva, Israel

The Tel Aviv Sourasky Medical Center

🇮🇱

Tel Aviv, Israel

Azienda Ospedaliero Universitaria di Modena

🇮🇹

Modena, Emilia-Romagna, Italy

Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori

🇮🇹

Meldola (fc), Forli Cesena, Italy

Istituto Europeo di Oncologia

🇮🇹

Milano, Italy

A.O.U. di Modena

🇮🇹

Modena, Italy

Federico II University

🇮🇹

Napoli, Italy

Azienda Ospedaliera di Perugia

🇮🇹

Perugia, Italy

UO Ematologia Ravenna

🇮🇹

Ravenna, Italy

Azienda Unita Sanitaria Locale Irccs Arcispedale Santa Maria Nuova

🇮🇹

Reggio Emilia, Italy

Azienda Sanitaria Universitaria del Friuli Centrale

🇮🇹

Udine, Italy

Matopolskie Centrum Medyczne S.C.

🇵🇱

Krakow, Malopolskie, Poland

Szpital Uniwersytecki Nr2 Bydgoszcz

🇵🇱

Bydgoszcz, Poland

Uniwersyteckie Centrum Kliniczne

🇵🇱

Gdansk, Poland

Pratia Onkologia Katowice

🇵🇱

Katowice, Poland

Szpital Szpecjalistyczny w Walbrzychu

🇵🇱

Walbrzych, Poland

Hospital Universitario Central de Asturias

🇪🇸

Oviedo, Asturas, Spain

Hospital Universitario Central De Asturias

🇪🇸

Oviedo, Asturias, Spain

Parc Tauli Sabadell Hospital Universitari

🇪🇸

Sabadell, Barcelona, Spain

Hospital Universitari Mutua Terrassa

🇪🇸

Terrassa, Barcelona, Spain

Hospital Universitario Puerta de Hierro - Majadahonda

🇪🇸

Majadahonda, Madrid, Spain

Hospital Universitario Quiron Salud Madrid

🇪🇸

Pozuelo de Alarcon, Madrid, Spain

Clinica Universidad de Navarra - Madrid

🇪🇸

Madrid, Spain

Hospital Universitario Infanta Leonor

🇪🇸

Madrid, Spain

Hospital Universitario Ramon y Cajal

🇪🇸

Madrid, Spain

Hospital Universitario Fundacion Jimenez Diaz

🇪🇸

Madrid, Spain

Hospital Universitario 12 de Octubre

🇪🇸

Madrid, Spain

Clinica Universidad de Navarra- Pamplona

🇪🇸

Pamplona, Spain

Hospital Universitario de Salamanca

🇪🇸

Salamanca, Spain

Hospital Universitario Virgen del Rocio

🇪🇸

Sevilla, Spain

Hospital General Universitario de Toledo

🇪🇸

Toledo, Spain

Instituto Valenciano de Oncologia

🇪🇸

Valencia, Spain

Chang Gung Memorial Hospital Kaohsiung

🇨🇳

Kaohsiung City, Taiwan

Kaohsiung Medical University Hospital

🇨🇳

Kaohsiung, Taiwan

Taipei Medical University - Shuang Ho Hospital

🇨🇳

New Taipei City, Taiwan

Tri-Service General Hospital

🇨🇳

Taipei City, Taiwan

Taipei Medical University Multipal Wan Fang University

🇨🇳

Taipei, Taiwan

Chulalongkorn University

🇹🇭

Bangkok, Krung Thep Maha Nakhon [Bangko], Thailand

Khon Kaen University

🇹🇭

Khon Kaen, Thailand

Dr. Abdurrahman Yurtaslan Oncology Training and Research Hospital

🇹🇷

Yenimahalle, Ankara, Turkey

Gazi University

🇹🇷

Ankara, Central Anatolia, Turkey

Sakarya University

🇹🇷

Sakarya, Serdivan, Turkey

Tekirdag Namik Kemal University Hospital

🇹🇷

Tekirdag, Suleymanpasa, Turkey

Liv Hospital Ankara

🇹🇷

Ankara, Turkey

VKV American Hopital

🇹🇷

Istanbul, Turkey

Istanbul University

🇹🇷

Istanbul, Turkey

Erci̇yes Uni̇versi̇ty

🇹🇷

Kayseri, Turkey

Ondokuz Mayıs University

🇹🇷

Samsun, Turkey

Zonguldak Bulent Ecevit University

🇹🇷

Zonguldak, Turkey

Royal Cornwall Hospital

🇬🇧

Truro, Cornwall, United Kingdom

University Hospitals Birmingham NHS Foundation Trust

🇬🇧

Birmingham, West Midlands, United Kingdom

NHS Grampian: Aberdeen Royal Infirmary

🇬🇧

Aberdeen, United Kingdom

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