Comparing Rituximab and Mosunetuzumab Drug Treatments for People With Low Tumor Burden Follicular Lymphoma

Randomized Phase III Study of Mosunetuzumab vs. Rituximab for Low Tumor Burden Follicular Lymphoma

This phase III trial compares the effectiveness of rituximab to mosunetuzumab in treating patients with follicular lymphoma with a low tumor burden. Rituximab is a monoclonal antibody. It binds to a protein called CD20, which is found on B cells (a type of white blood cell) and some types of cancer cells. This may help the immune system kill cancer cells. Mosunetuzumab is a monoclonal antibody that may interfere with the ability of cancer cells to grow and spread. It is not yet known if giving rituximab or mosunetuzumab works better in treating patients with follicular lymphoma with a low tumor burden.

Study Overview

• Status: Not yet recruiting
• Conditions: Classic Follicular Lymphoma; Follicular Lymphoma With Unusual Cytological Features
• Intervention / Treatment: Procedure: Biospecimen Collection; Procedure: Positron Emission Tomography; Biological: Rituximab; Biological: Rituximab and Hyaluronidase Human; Biological: Mosunetuzumab; Procedure: Computed Tomography

Detailed Description

PRIMARY OBJECTIVES:

I. To compare the 3-year milestone progression free survival (PFS) probabilities in participants with previously untreated, low tumor burden follicular lymphoma randomized to the rituximab arm versus the mosunetuzumab arm.

II. To compare progression free survival (PFS) in participants with previously untreated, low tumor burden follicular lymphoma randomized to the rituximab arm versus the mosunetuzumab arm.

SECONDARY OBJECTIVES:

I. To compare overall survival (OS) between participants randomized to rituximab versus mosunetuzumab.

II. To compare overall response rates at the Week 40 assessment between participants randomized to rituximab versus mosunetuzumab.

III. To compare event free survival (EFS) between participants randomized to rituximab versus mosunetuzumab.

IV. To compare the frequency and severity of toxicities between participants randomized to rituximab versus mosunetuzumab.

V. To compare the restricted chance of longer PFS (2-6 years) between participants randomized to rituximab versus mosunetuzumab.

BANKING OBJECTIVE:

I. To bank specimens for future correlative studies.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM I: Patients receive rituximab intravenously (IV) on day 1 of cycle 1 and receive rituximab and hyaluronidase subcutaneously (SC) on days 8, 15 and 22 of cycle 1 and SC on day 1 of subsequent cycles. Cycles repeat every 56 days for up to 5 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo computed tomography (CT) scan and/or positron emission tomography (PET)/CT and blood sample collection on study and during follow up.

ARM II: Patients receive mosunetuzumab SC on days 1, 8 and 15 of cycle 1 and on day 1 of subsequent cycles. Cycles repeat every 21 days for up to 8 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo CT scan and/or PET/CT and blood sample collection on study and during follow up.

After completion of study treatment, patients are followed up every 6 months for 5 years and then yearly for a total of 10 years.

• Study Type: Interventional
• Enrollment (Estimated): 600
• Phase: Phase 3

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Participants must have a histologically confirmed diagnosis of classic follicular lymphoma (cFL) defined as: Follicular growth pattern, composed of centrocytes and centroblasts and harbor the IGH:BCL2 fusion. cFL was previously categorized as grade 1-3A per World Health Organization (WHO)-HAEM4R, but grading of classic follicular lymphoma (FL) is no longer mandatory.

  • NOTE: Participants with follicular lymphoma with uncommon features (uFL) are eligible, including FL with diffuse growth pattern with large tumor in the inguinal region: Absence of IGH:BCL2 fusion, frequent STAT6 mutations along with 1p36 deletion or TNFRSF14 mutation
• Participants must not have follicular lymphoma with "blastoid" or "large centrocyte" cytological features, or follicular large B-cell lymphoma (FLBL) (previously categorized as follicular lymphoma grade 3B)

• Participants must have low-tumor burden follicular lymphoma defined as:

  • Nodal or extra-nodal tumor mass with diameter less than 7 cm in its greater diameter
  • Involvement of no more than 3 nodal or extra nodal sites with diameter greater than 3 cm.
  • Absence of B symptoms
  • No symptomatic splenomegaly
  • No compression syndrome (ureteral, orbital, gastrointestinal)
  • No pleural or peritoneal serous effusion related to follicular lymphoma
• Participants must have Ann Arbor stage II, III, or IV follicular lymphoma. Participants with stage I disease may be included if they do not wish to undergo radiation or are not candidates for radiation

• Participants must have staging imaging performed within 49 days prior to registration, as follows. PET-CT baseline scans are preferred. If a baseline PET-CT scan cannot be obtained, CT scans of the chest, abdomen, and pelvis, along with a bone marrow biopsy, are acceptable. If CT scans are used for staging at baseline, a CT scan of the neck is recommended. All measurable dominant lesions must be assessed within 49 days prior to registration. Tests to assess non-measurable disease must be performed within 49 days prior to registration. All disease must be assessed and documented on the Baseline Tumor Assessment Form.

  • NOTE: if the initial evaluation is insufficient to detect measurable disease, treating investigators may obtain a CT scan with contrast
• Participants must have bi-dimensionally measurable disease (at least one lesion with longest diameter > 1.5 cm)
• Participants must not have had prior systemic therapy for follicular lymphoma. Radiation therapy for a previous diagnosis of early-stage follicular lymphoma is allowed
• Participant must be ≥ 18 years of age at the time of registration
• Participant must have Zubrod performance status of 0-2
• Participant must have a complete medical history and physical exam within 28 days prior to registration
• Leukocytes ≥ 3 x 10^3/uL (within 28 days prior to registration)
• Hemoglobin > 9.0 g/dL (within 28 days prior to registration)
• Absolute neutrophil count ≥ 1.5 x 10^3/uL (within 28 days prior to registration)
• Platelets ≥ 100 x 10^3/uL (within 28 days prior to registration)
• Total bilirubin ≤ 2 x institutional upper limit of normal (ULN) unless history of Gilbert's disease. Participants with history of Gilbert's disease must have total bilirubin ≤ 5 x institutional ULN (within 28 days prior to registration)
• Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ≤ 3 × institutional ULN (within 28 days prior to registration)
• Lactate dehydrogenase (LDH) < institutional ULN (within 28 days prior to registration)
• Participants must have a creatinine ≤ the institutional upper limit of normal (IULN) OR calculated creatinine clearance ≥ 30 mL/min using the following Cockcroft-Gault Formula. This specimen must have been drawn and processed within 28 days prior to registration
• Participants must not have uncontrolled infection before initiation of study treatment in the opinion of the treating investigators
• Participants must not have uncontrolled diabetes within 14 days prior to registration in the opinion of the treating investigators
• Participants must not have uncontrolled blood pressure and hypertension within 14 days prior to registration in the opinion of the treating investigators
• Participants with known human immunodeficiency virus (HIV)-infection must be on effective anti-retroviral therapy at registration and have undetectable viral load test on the most recent test results obtained within 6 months prior to registration
• Participants with evidence of chronic hepatitis B virus (HBV) infection must have undetectable HBV viral load while on suppressive therapy on the most recent test results obtained within 6 months prior to registration, if indicated. Participants with a positive total hepatitis (Hep) B core antibody and negative hepatitis B virus surface antigen (HBsAg) at screening are at high risk for reactivation and should receive prophylactic antivirals (e.g., entecavir) before and throughout the treatment
• Participants must not have active autoimmune disease requiring systemic therapy
• Participants must not have had undergone organ transplants requiring ongoing systemic immunosuppressive therapy
• Participants with a history of hepatitis C virus (HCV) infection must have been treated and cured. Participants currently being treated for HCV infection must have undetectable HCV viral load test on the most recent test results obtained within 6 months prior to registration, if indicated
• Participants must not have known chronic active Epstein Barr Virus infection (CAEBV); testing in asymptomatic participants is not required
• Participants must not have a positive test result for COVID-19 within seven (7) days prior to registration
• Participants must not have a prior or concurrent malignancy whose natural history or treatment (in the opinion of the treating physician) has the potential to interfere with the safety or efficacy assessment of the investigational regimen
• Participants must not have a history of confirmed progressive multifocal leukoencephalopathy (PML)
• Participants must not have received allogeneic stem cell transplantation
• Participants must not have a history of macrophage activation syndrome (MAS) or hemophagocytic lymphohistiocytosis (HLH)
• Participants with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, must have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. Participant must not have significant cardiovascular disease such as class III or IV cardiac disease, myocardial infarction within 6 months prior to registration. Participants with unstable arrhythmias, or unstable angina, should be excluded
• Participants must not be pregnant or nursing (nursing includes breast milk fed to an infant by any means, including from the breast, milk expressed by hand, or pumped). Individuals who are of reproductive potential must have agreed to use an effective contraceptive method with details provided as a part of the consent process. A person who has had menses at any time in the preceding 12 consecutive months or who has semen likely to contain sperm is considered to be of "reproductive potential." In addition to routine contraceptive methods, "effective contraception" also includes refraining from sexual activity that might result in pregnancy and surgery intended to prevent pregnancy (or with a side-effect of pregnancy prevention) including hysterectomy, bilateral oophorectomy, bilateral tubal ligation/occlusion, and vasectomy with testing showing no sperm in the semen
• Participants must be offered the opportunity to participate in specimen banking. With participant consent, specimens must be collected and submitted via the Southwest Oncology Group (SWOG) Specimen Tracking System

• NOTE: As a part of the Oncology Patient Enrollment Network (OPEN) registration process the treating institution's identity is provided in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered in the system.

  • Participants must be informed of the investigational nature of this study and must sign and give informed consent in accordance with institutional and federal guidelines
  • For participants with impaired decision-making capabilities, legally authorized representatives may sign and give informed consent on behalf of study participants in accordance with applicable federal, local, and Central Institutional Review Board (CIRB) regulations

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm I (Rituximab, rituximab and hyaluronidase); Patients receive rituximab IV on day 1 of cycle 1 and receive rituximab and hyaluronidase SC on days 8, 15 and 22 of cycle 1 and SC on day 1 of subsequent cycles. Cycles repeat every 56 days for up to 5 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo CT scan and/or PET/CT and blood sample collection on study and during follow up.	Procedure: Biospecimen Collection; Undergo blood sample collection; Other Names: Biological Sample Collection; Biospecimen Collected; Specimen Collection; Procedure: Positron Emission Tomography; Undergo PET/CT scan; Other Names: Medical Imaging, Positron Emission Tomography; PET; PET Scan; Positron Emission Tomography Scan; Positron-Emission Tomography; proton magnetic resonance spectroscopic imaging; PT; Positron emission tomography (procedure); Biological: Rituximab; Given IV; Other Names: Rituxan; MabThera; ABP 798; BI 695500; C2B8 Monoclonal Antibody; Chimeric Anti-CD20 Antibody; CT-P10; IDEC-102; IDEC-C2B8; IDEC-C2B8 Monoclonal Antibody; Monoclonal Antibody IDEC-C2B8; PF-05280586; Riabni; Rituximab ABBS; Rituximab ARRX; Rituximab Biosimilar ABP 798; Rituximab Biosimilar BI 695500; Rituximab Biosimilar CT-P10; Rituximab Biosimilar GB241; Rituximab Biosimilar IBI301; Rituximab Biosimilar JHL1101; Rituximab Biosimilar PF-05280586; Rituximab Biosimilar RTXM83; Rituximab Biosimilar SAIT101; Rituximab Biosimilar SIBP-02; rituximab biosimilar TQB2303; Rituximab PVVR; Rituximab-arrx; Rituximab-pvvr; RTXM83; Ruxience; Truxima; Ikgdar; Mabtas; Rituximab-abbs; Biological: Rituximab and Hyaluronidase Human; Given SC; Other Names: Rituxan Hycela; Rituximab Plus Hyaluronidase; Rituximab/Hyaluronidase; Rituximab/Hyaluronidase Human; Procedure: Computed Tomography; Undergo CT and/or PET/CT scan; Other Names: CT; CAT; CAT Scan; Computed Axial Tomography; Computerized Axial Tomography; Computerized Tomography; CT Scan; tomography; Computerized axial tomography (procedure); Computerized Tomography (CT) scan
Experimental: Arm II (Mosunetuzumab); Patients receive mosunetuzumab SC on days 1, 8 and 15 of cycle 1 and on day 1 of subsequent cycles. Cycles repeat every 21 days for up to 8 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo CT scan and/or PET/CT and blood sample collection on study and during follow up.	Procedure: Biospecimen Collection; Undergo blood sample collection; Other Names: Biological Sample Collection; Biospecimen Collected; Specimen Collection; Procedure: Positron Emission Tomography; Undergo PET/CT scan; Other Names: Medical Imaging, Positron Emission Tomography; PET; PET Scan; Positron Emission Tomography Scan; Positron-Emission Tomography; proton magnetic resonance spectroscopic imaging; PT; Positron emission tomography (procedure); Biological: Mosunetuzumab; Given SC; Other Names: RO7030816; BTCT4465A; Anti-CD20 x Anti-CD3 Bispecific Monoclonal Antibody BTCT4465A; BTCT 4465A; BTCT-4465A; CD20/CD3 BiMAb BTCT4465A; RG 7828; RG-7828; RG7828; Lunsumio; Mosunetuzumab-axgb; Procedure: Computed Tomography; Undergo CT and/or PET/CT scan; Other Names: CT; CAT; CAT Scan; Computed Axial Tomography; Computerized Axial Tomography; Computerized Tomography; CT Scan; tomography; Computerized axial tomography (procedure); Computerized Tomography (CT) scan

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
3-year milestone progression free survival (PFS)	From date of registration to date of first observation of progressive disease, transformation to diffuse large B cell lymphoma, or death due to any cause, up to 3 years
PFS	From date of registration to date of first observation of progressive disease, transformation to diffuse large B cell lymphoma, or death due to any cause, up to 10 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival	Will be estimated using the method of Kaplan-Meier and compared between treatment arms using cox regression model.	Up to 10 years
Overall response rate		At week 40
Event free survival (EFS)	Will be estimated using the method of Kaplan-Meier and compared between treatment arms using cox regression model.	From date of registration to date of first occurrence of EFS event, up to 10 years
Incidence of adverse events	Will be evaluated using the Common Terminology Critiera for Adverse Events version 5 items.	Up to end of treatment
Restricted chance of longer PFS		Up to 10 years

Collaborators and Investigators

• Sponsor: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Nilanjan Ghosh, SWOG Cancer Research Network

Study record dates

Study Major Dates

• Study Start (Estimated): August 31, 2024
• Primary Completion (Estimated): March 31, 2032
• Study Completion (Estimated): March 31, 2032

Study Registration Dates

• First Submitted: March 27, 2024
• First Submitted That Met QC Criteria: March 27, 2024
• First Posted (Actual): March 29, 2024

Study Record Updates

• Last Update Posted (Actual): April 5, 2024
• Last Update Submitted That Met QC Criteria: April 4, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma; Lymphoma, Follicular; Physiological Effects of Drugs; Antirheumatic Agents; Antineoplastic Agents; Immunologic Factors; Antibodies; Immunoglobulins; Rituximab; Antibodies, Monoclonal; Antineoplastic Agents, Immunological; Antibodies, Bispecific
• Other Study ID Numbers: NCI-2024-02361 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); U10CA180888 (U.S. NIH Grant/Contract); S2308 (Other Identifier: CTEP)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No