A Study to Assess the Anti-Tumor Activity and Safety of Odronextamab in Adult Patients With B-cell Non-Hodgkin Lymphoma Who Have Been Previously Treated With Other Cancer Therapies
- Registration Number
- NCT03888105
- Lead Sponsor
- Regeneron Pharmaceuticals
- Brief Summary
This study is researching an investigational drug, odronextamab, in adult patients B-cell non-Hodgkin's lymphoma (B-NHL).
The main purpose of this study is to assess the effectiveness of odronextamab in destroying cancer cells and to learn more about the safety of odronextamab.
The study is looking at several other research questions, including:
* To see if odronextamab works to destroy cancer cells
* Side effects that may be experienced by people taking odronextamab
* How odronextamab works in the body
* How much odronextamab is present in the blood
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 576
-
For the FL grade 1-3a cohort only: Central histopathologic confirmation of the FL Grade 1 to 3a diagnosis must be obtained before study enrollment. Patients with FL grade 3b are ineligible for this cohort but may be included in the "other B-NHL" cohort. Follicular lymphoma subtyping is based on the World Health Organization (WHO) classification (Swerdlow, 2017).
-
Disease-specific cohorts:
Patients should in the judgment of the investigator require systemic therapy for lymphoma at the time of study enrollment.
- FL grade 1-3a cohort: Patients with FL grade 1-3a that has relapsed after or is refractory to at least 2 prior lines of systemic therapy, as defined in the protocol
- DLBCL cohort: Patients with DLBCL that has relapsed after or is refractory to at least 2 prior lines of systemic therapy as defined in the protocol
- MCL after BTK inhibitor therapy cohort: Patients with MCL who have relapsed or refractory disease to at least one prior line of systemic therapy and had prior treatment with a Bruton's tyrosine kinase (BTK) inhibitor.
- MZL cohort: Patients with MZL that have relapsed or is refractory to at least 2 prior lines of systemic therapy.
- Other B-NHL cohort: Patients with B-NHL other than FL grade 1-3a, DLBCL, MCL, or MZL that has relapsed after or is refractory to at least 2 prior lines of systemic therapy as defined in the protocol. New enrollment stopped for patients with Burkitt lymphoma and Burkitt-like lymphoma.
-
Measurable disease on cross sectional imaging as defined in the protocol documented by diagnostic imaging (computed tomography (CT), or magnetic resonance imaging (MRI)
-
Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
-
Adequate bone marrow, hepatic, and renal function as defined in the protocol
Key
- Primary central nervous system (CNS) lymphoma or known involvement by non-primary CNS Non-Hodgkin Lymphoma (NHL) (suspected CNS lymphoma should be evaluated by lumbar puncture, as appropriate, in addition to the mandatory head CT or MRI).
- Treatment with any systemic anti-lymphoma therapy within 5 half-lives or within 28 days prior to first administration of study drug, whichever is shorter.
- History of allogeneic stem cell transplantation
- Continuous systemic corticosteroid treatment with more than 10 mg per day of prednisone or anti-inflammatory equivalent within 72 hours of start of study drug
- History of neurodegenerative condition or CNS movement disorder. Patients with a history of seizure within 12 months prior to study enrollment are excluded
- Another malignancy except B-NHL in the past 5 years, with the exception of non-melanoma skin cancer that has undergone potentially curative therapy or in situ cervical carcinoma, or any other tumor that has been deemed to be effectively treated with definitive local control and with curative intent.
- Uncontrolled infection with human immunodeficiency virus (HIV), hepatitis B or hepatitis C infection; cytomegalovirus (CMV) infection as noted by detectable levels on a blood polymerase chain reaction (PCR) assay as defined in the protocol or other uncontrolled infections
- Known hypersensitivity to both allopurinol and rasburicase
- Prior treatment with an anti-CD20 x anti-CD3 bispecific therapy
Note: Other protocol-defined Inclusion/Exclusion criteria apply
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description FL Odronextamab Follicular lymphoma grade 1-3a cohort DLBCL Odronextamab Diffuse large B-cell lymphoma cohort MZL Odronextamab Marginal Zone Lymphoma cohort MCL Odronextamab Mantle Cell Lymphoma cohort Other B-NHL Odronextamab Other B-cell non-Hodgkin lymphoma cohort (excluding FL Grade 1-3a, DLBCL, MCL, MZL, Waldenström macroglobulinemia \[WM\]); Patients with a current diagnosis of mixed histology of B-NHL with an aggressive component (such as concurrent FL and DLBCL) will be allowed
- Primary Outcome Measures
Name Time Method Objective response rate (ORR), as assessed by independent central review Up to 52 weeks of study treatment FL grade 1-3a/MZL
ORR, as assessed by independent central review Up to 36 weeks of study treatment DLBCL/MCL/Other B-NHL
- Secondary Outcome Measures
Name Time Method ORR, as assessed by the local investigator Up to 36 weeks of study treatment DLBCL/MCL/Other B-NHL
Complete response (CR) rate, as assessed by the local investigator Up to 52 weeks of study treatment FL grade 1-3a/MZL
CR rate, as assessed by independent central review Up to 36 weeks of study treatment DLBCL/MCL/Other B-NHL
CR rate, as assessed by the local investigator Up to 36 weeks of study treatment DLBCL/MCL/Other B-NHL
Progression-free survival (PFS), as assessed by independent central review Approximately 194 weeks following the first dose PFS, as assessed by the local investigator Approximately 194 weeks following the first dose Overall survival (OS) Approximately 194 weeks following the first dose Duration of response (DOR), as assessed by independent central review Approximately 194 weeks following the first dose DOR, as assessed by the local investigator Approximately 194 weeks following the first dose DCR, as assessed by independent central review Up to 36 weeks of study treatment DLBCL/MCL/Other B-NHL
DCR, as assessed by the local investigator Up to 36 weeks of study treatment DLBCL/MCL/Other B-NHL
Incidence of anti-drug antibodies (ADA) to odronextamab over time 12 weeks following end of treatment Incidence of neutralizing antibodies (Nab) to odronextamab over time 12 weeks following end of treatment Changes in scores of patient-reported outcomes as measured by European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Cancer-30 (EORTC-QLQ-C30) Approximately 194 weeks following the first dose The EORTC QLQ-C30 is a self-reported, 30-item generic questionnaire developed to assess 15 domains: global health status scale, five functional scales (physical, role, emotional, cognitive, and social functioning) and nine symptom scales (fatigue, nausea, vomiting, pain, dyspnea, insomnia, appetite loss, constipation, diarrhea and financial difficulties).
Disease control rate (DCR), as assessed by independent central review Up to 52 weeks of study treatment FL grade 1-3a/MZL
DCR, as assessed by the local ivestigator Up to 52 weeks of study treatment FL grade 1-3a/MZL
Incidence and severity of treatment emergent adverse events (TEAEs) Approximately 194 weeks following the first dose Concentration of odronextamab 12 weeks following end of treatment End of infusion \[EOI\]; Concentration at a specified time t \[Ct\])
Titer of anti-drug antibodies to odronextamab over time 12 weeks following end of treatment Changes in scores of patient-reported outcomes as measured by Functional Assessment of Cancer Treatment-Lymphoma (FACT-Lym) Approximately 194 weeks following the first dose Composed of the FACT-G plus the 15-item Lymphoma Subscale (LymS).
Changes in scores of patient-reported outcomes as measured by EuroQol-5 Dimensions-3 Levels (EQ-5D-3L) Approximately 194 weeks following the first dose The EQ-5D-3L is a standardized instrument for use as a measure of health outcome. It is a health questionnaire that consists of the EQ-5D descriptive system and the EQ visual analogue scale (EQ VAS). The EQ-5D-3L descriptive system comprises the following 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 3 levels: no problems, some problems, extreme problems.
Trial Locations
- Locations (140)
Rush University Medical Center
🇺🇸Chicago, Illinois, United States
University of Iowa
🇺🇸Iowa City, Iowa, United States
Norton Cancer Institute
🇺🇸Louisville, Kentucky, United States
Tufts Medical Center
🇺🇸Boston, Massachusetts, United States
Beth Israel Deaconess Medical Center
🇺🇸Boston, Massachusetts, United States
Rogel Cancer Center
🇺🇸Ann Arbor, Michigan, United States
Mayo Clinic - Rochester
🇺🇸Rochester, Minnesota, United States
Saint Louis University Hospital
🇺🇸Saint Louis, Missouri, United States
John Theurer Cancer Center at Hackensack UMC
🇺🇸Hackensack, New Jersey, United States
Morristown Medical Center
🇺🇸Morristown, New Jersey, United States
Scroll for more (130 remaining)Rush University Medical Center🇺🇸Chicago, Illinois, United States