Relapsed/Refractory Follicular Lymphoma, Relapsed/Refractory Marginal Zone Lymphoma (R/R MZL)
Conditions
Keywords
Relapsed/Refractory Follicular Lymphoma, Relapsed/Refractory Marginal Zone Lymphoma, Non-Hodgkin lymphomas, Indolent lymphomas, Odronextamab
Brief summary
This study is researching an experimental drug called odronextamab (referred to as study drug), in combination with lenalidomide. The study is focused on participants who have one of two types of cancer: Follicular Lymphoma (FL) or Marginal Zone Lymphoma (MZL) that has come back after treatment (called "relapsed") or did not respond to treatment (called "refractory"). FL and MZL are subtypes of Non-Hodgkin 's Lymphoma (NHL). This study will be made up of two parts (Part 1 not randomized, Part 2 randomized - controlled). The aim of Part 1 of the study is to see how safe and tolerable the study drug is when used in combination with lenalidomide, in participants with FL or MZL, and to determine the dose of the study drug to be used in Part 2 of this study. This combination is considered "first-in-human" as it has not been tested as a combination treatment in humans before. The aim of Part 2, of the study is to assess how well the combination of the study drug and lenalidomide works compared to the combination of rituximab (called "the comparator drug") and lenalidomide. The combination of comparator drug and lenalidomide is the current standard-of-care treatment for relapsed/refractory FL and/or MZL. 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 in combination with lenalidomide * 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
Interventions
DRUGOdronextamab
Administered per the protocol
DRUGLenalidomide
Administered per the protocol
DRUGRituximab
Administered per the protocol
Sponsors
Regeneron Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: 1. Local histologic confirmation of FL grade 1-3a or MZL (nodal, splenic, or extra nodal MZL) as assessed by the investigator, as described in the protocol. 2. Must have refractory disease or relapsed after at least 1 prior line (with a duration of at least 2 cycles) of systemic chemo-immunotherapy or immunotherapy. Prior systemic therapy should have included at least one anti-Cluster of Differentiation 20 (CD20) monoclonal antibody, and participant should meet indication for treatment, as described in the protocol. 3. Have measurable disease on cross sectional imaging documented by diagnostic Computed Tomography \[CT\], or Magnetic Resonance Imaging \[MRI\] imaging, as described in the protocol. 4. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2. 5. Adequate hematologic and organ function, as described in the protocol. 6. All study participants must: 1. Have an understanding that lenalidomide could have a potential teratogenic risk. 2. Agree to abstain from donating blood while taking study drug therapy and for 28 days after discontinuation of lenalidomide. 3. Agree not to share study medication with another person. 4. Agree to be counseled about pregnancy precautions and risk of fetal exposure associated with lenalidomide. Key
Exclusion criteria
1. Primary Central Nervous System (CNS) lymphoma or known involvement (either current or prior history of CNS involvement) by non-primary CNS NHL, as described in the protocol. 2. Participants with current or past histological evidence of high-grade or diffuse large B-cell lymphoma, or any histology other than FL grade 1-3a or MZL. 3. History of or current relevant CNS pathology, as described in the protocol. 4. A malignancy other than NHL (inclusion diagnosis) unless the participant is adequately and definitively treated and is cancer free for at least 3 years, with the exception of localized prostate cancer treated with hormone therapy or local radiotherapy (ie, pellets), cervical carcinoma in situ, breast cancer in situ, or nonmelanoma skin cancer that was definitively treated. 5. 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. 6. Allergy/hypersensitivity to study drugs or excipients. as described in the protocol. 7. Active infection as defined in the protocol. Note: Other protocol-defined Inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Dose Limiting Toxicities (DLTs) for odronextamab in combination with lenalidomide | Up to 35 days | Part 1 |
| Incidence of Treatment Emergent Adverse Events (TEAEs) for odronextamab in combination with lenalidomide | Up to 2 years | Part 1 |
| Severity of TEAEs for odronextamab in combination with lenalidomide | Up to 2 years | Part 1 |
| Progression-Free Survival (PFS) as assessed by Independent Central Review (ICR) | Up to 5 years | Part 2 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Odronextamab concentrations in serum | Up to 30 months | Part 1 and Part 2 |
| Incidence of Anti-Drug Antibodies (ADA) to odronextamab | Up to 30 months | Part 1 and Part 2 |
| Magnitude of ADAs to odronextamab | Up to 30 months | Part 1 and Part 2 |
| Best Overall Response (BOR) as assessed by investigator review | Up to 30 months | Part 1 and Part 2 |
| Duration of Response (DOR) as assessed by investigator review | Up to 5 years | Part 1 and Part 2 |
| PFS as assessed by investigator review | Up to 5 years | Part 1 and Part 2 |
| Complete Response (CR) as assessed by ICR | Up to 30 months | Part 2 |
| BOR as assessed by ICR | Up to 30 months | Part 2 |
| Overall Survival (OS) | Up to 5 years | Part 2 |
| Event Free Survival (EFS) as assessed by ICR | Up to 5 years | Part 2 |
| EFS as assessed by local investigator review | Up to 5 years | Part 2 |
| DOR as assessed by ICR | Up to 5 years | Part 2 |
| Time To Next anti-lymphoma Treatment (TTNT) | Up to 5 years | Part 2 |
| Incidence of TEAEs for odronextamab in combination with lenalidomide versus R2 | Up to 2 years | Part 2 |
| Severity of TEAEs for odronextamab in combination with lenalidomide versus R2 | Up to 2 years | Part 2 |
| Overall change in Patient Reported Outcomes (PROs) as measured by scores of European Organisation for Research and Treatment of Cancer Quality-of-Life Questionnaire (EORTC QLQC30) | 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 GHS/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. |
| Overall change in PROs as measured by scores of Functional Assessment of Cancer Therapy-Lymphoma Subscale (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. |
| Overall change in PROs as measured by scores of 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 from first assessment in Patient Global Impression on 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). |
| Change from first assessment in Patient Global Impression on 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 from first assessment in the Global Population item 5 (GP5) items of the Functional Assessment of Cancer Therapy-General (FACT-G) questionnaire | 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). |
Countries
Australia, Austria, Belgium, Brazil, Czechia, France, Germany, Israel, Italy, Malaysia, Poland, South Korea, Spain, Taiwan, Thailand, Turkey (Türkiye), United Kingdom, United States
Contacts
CONTACTClinical Trials Administrator
STUDY_DIRECTORClinical Trial Management
Regeneron Pharmaceuticals
Outcome results
None listed