Rituximab With or Without Yttrium Y-90 Ibritumomab Tiuxetan in Treating Patients With Untreated Follicular Lymphoma

NCT02320292 | Terminated Phase 3 Results DMC

• 3 other identifiers: LS138DNCI-2014-0247614-003066
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

This phase III trial studies rituximab and yttrium Y-90 ibritumomab tiuxetan to see how well they work compared to rituximab alone in treating patients with untreated follicular lymphoma. Immunotherapy with monoclonal antibodies, such as nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Radioactive substances linked to monoclonal antibodies can bind to cancer cells and give off radiation which may help kill cancer cells. It is not yet known whether rituximab works better with or without yttrium Y-90 ibritumomab tiuxetan in treating follicular lymphoma.

Conditions

Ann Arbor Stage I Grade 1 Follicular Lymphoma; Ann Arbor Stage I Grade 2 Follicular Lymphoma; Ann Arbor Stage II Grade 1 Contiguous Follicular Lymphoma; Ann Arbor Stage II Grade 1 Non-Contiguous Follicular Lymphoma; Ann Arbor Stage II Grade 2 Contiguous Follicular Lymphoma; Ann Arbor Stage II Grade 2 Non-Contiguous Follicular Lymphoma; Ann Arbor Stage III Grade 1 Follicular Lymphoma; Ann Arbor Stage III Grade 2 Follicular Lymphoma; Ann Arbor Stage IV Grade 1 Follicular Lymphoma; Ann Arbor Stage IV Grade 2 Follicular Lymphoma

Outcome Measures

Primary Outcomes (1)

• Complete Response (CR) Rate at the 6-month Disease Assessment

  Will be compared between the two arms. The percentage of patients in each response category (e.g., CR, partial remission, stable disease, relapse/progressive disease) will also be tabulated by arm. The proportion of patients who have a CR at 6 months will be evaluated and compared between the two treatment regimens using a two-sided alpha=0.05 continuity corrected Cochran-Mantel-Haenszel test with stratification factors.

  6 months

Secondary Outcomes (4)

• Progression-free Survival (PFS)

  Time from registration to the earliest date documentation of disease progression or death due to any cause, assessed up to 5 years

• Time to Any Therapy (TTNT)

  Time from registration to the date of initiation of any treatment for follicular lymphoma, assessed up to 5 years

• Time to Chemotherapy (TTC)

  Time from registration to the date of initiation of chemotherapy for follicular lymphoma, assessed up to 5 years

• Incidence of Adverse Events

  Up to 5 years

Other Outcomes (9)

• Incidence of Exon 2 bcl2 Mutations

  Baseline

• Change in Quantification of Tissue Tregs and Tissue Monocytes on Study Tumor Biopsies

  Baseline to 6 months

• Change in Serum Cytokines

  Baseline to 6 months

Study Arms (2)

Arm A (rituximab)

ACTIVE COMPARATOR

Patients receive rituximab IV on days 1, 8, 15, and 22.

Other: Quality-of-Life Assessment; Biological: Rituximab

Arm B (rituximab, yttrium Y-90 ibritumomab tiuxetan)

EXPERIMENTAL

Patients receive rituximab IV on days 1 and 8 and yttrium Y-90 ibritumomab tiuxetan over 10 minutes on day 8.

Other: Quality-of-Life Assessment; Biological: Rituximab; Radiation: Yttrium Y-90 Ibritumomab Tiuxetan

Interventions

Quality-of-Life Assessment OTHER

Ancillary studies

Also known as: Quality of Life Assessment

Arm A (rituximab); Arm B (rituximab, yttrium Y-90 ibritumomab tiuxetan)

Rituximab BIOLOGICAL

Given IV

Also known as: ABP 798, BI 695500, C2B8 Monoclonal Antibody, Chimeric Anti-CD20 Antibody, CT-P10, IDEC-102, IDEC-C2B8, IDEC-C2B8 Monoclonal Antibody, MabThera, Monoclonal Antibody IDEC-C2B8, PF-05280586, Rituxan, Rituximab ABBS, 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 TQB2303, rituximab-abbs, RTXM83, Truxima

Arm A (rituximab); Arm B (rituximab, yttrium Y-90 ibritumomab tiuxetan)

Yttrium Y-90 Ibritumomab Tiuxetan RADIATION

Given IV

Also known as: IDEC-Y2B8, IDEC-Y2B8 monoclonal antibody, Y 90 Ibritumomab Tiuxetan, Y 90 Zevalin, Yttrium Y 90 Ibritumomab Tiuxetan, yttrium Y90 ibritumomab tiuxetan

Arm B (rituximab, yttrium Y-90 ibritumomab tiuxetan)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histological confirmation of follicular lymphoma grades I, II diagnosed within 12 months (365 days) prior to registration; NOTE: the day of biopsy should be used as day 1 of diagnosis for this calculation
• Stage I, II, III, or IV disease; NOTE: stage I disease are eligible only if the disease is not amenable to external beam radiation therapy
• No indication for chemotherapy; candidate for observation
• Measurable disease by tumor imaging with at least one lesion \>= 1.5 cm in at least one dimension
• Previously untreated; NOTE: this includes any chemotherapy or immunotherapy or RIT; patients who received corticosteroids for diseases other than lymphoma are eligible as long as prednisone dose is =\< 10 mg/day
• Low tumor burden as defined by Groupe d'Etudes des Lymphomes Folliculaires (GELF) criteria (2):
• No tumor mass (nodal or extranodal) \>= 7 cm in one dimension on computed tomography (CT)
• Fewer than 3 (2 or less) nodal masses \> 3 cm
• No systemic or B symptoms
• No splenomegaly greater than 16 cm by CT scan
• No risk of organ compression - ureteral, orbital, neurological, gastrointestinal
• No leukemic phase (\> 5.0 x 10\^9/L circulating FL cells in the blood as detected by complete blood count \[CBC\] with differential and smear)
• No cytopenias - absolute neutrophil count (ANC) \< 1000 or platelets \< 100,000
• Meet standard criteria for RIT:
• \< 25% marrow involvement with FL

You may not qualify if:

• Any of the following because this study involves an agent whose genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn are unknown:
• Pregnant women
• Nursing women
• Men or women of childbearing potential who are unwilling to employ adequate contraception for at least three months after completing study treatment
• Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens
• Patients known to be human immunodeficiency virus (HIV) positive and currently receiving antiretroviral therapy
• NOTE: These patients are excluded because it is unknown what effects prolonged B-cell depletion will have on these patient's immune system
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, uncontrolled cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
• Receiving any other investigational agent that would be considered as a treatment for the lymphoma
• Active other malignancy requiring treatment that would interfere with the assessments of response of the lymphoma to protocol treatment and would interfere with follow-up assessments through year 5
• Presence of central nervous system (CNS) lymphoma
• Known to have lymphoma related to HIV or acquired immune deficiency syndrome (AIDS)
• Abnormal renal function (serum creatinine \> 2 x ULN)
• Received prior external beam radiation therapy for another reason to \> 25% of active bone marrow
• Serious non-malignant disease such as active infection or other condition which in the opinion of the investigator would compromise other protocol objectives

Sponsors & Collaborators

• Mayo Clinic: lead

Study Sites (1)

Mayo Clinic in Rochester

Rochester, Minnesota, 55905, United States

Location

MeSH Terms

Interventions

Rituximab; CT-P10; ibritumomab tiuxetan

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Dr. Thomas E Witzig
• Organization: Mayo Clinic

witzig.thomas@mayo.edu

507-266-4994

Study Officials

• Thomas E. Witzig, M.D.

  Mayo Clinic in Rochester

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 15, 2014
• First Posted: December 19, 2014
• Study Start: February 11, 2015
• Primary Completion: February 28, 2021
• Study Completion: November 9, 2023
• Last Updated: July 9, 2025
• Results First Posted: July 18, 2023

Record last verified: 2023-11

Locations

US (1)