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Ann Arbor Stage I Grade 1 Follicular LymphomaPhase 3NCT02320292

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

A Phase 3 study testing Quality-of-Life Assessment, Rituximab and Yttrium Y-90 Ibritumomab Tiuxetan in people with Ann Arbor Stage I Grade 1 Follicular Lymphoma and Ann Arbor Stage I Grade 2 Follicular Lymphoma, run by Mayo Clinic at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Quality-of-Life Assessment, Rituximab and Yttrium Y-90 Ibritumomab Tiuxetan
Could I receive a placebo?
No, everyone receives an active treatment
How many people
20 participants
Where
1 siteUnited States
Study dates
11 Feb 2015to 9 Nov 2023
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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):
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  • 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
  • No evidence of myelodysplasia
  • Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1, or 2
  • Absolute neutrophil count (ANC) >= 1500/mm^3 obtained =< 28 days prior to registration
  • Platelet count >= 100,000/mm^3 =< 28 days prior to registration
  • Hemoglobin > 10.0 g/dL =< 28 days prior to registration
  • Total bilirubin =< 1.5 x upper limit of normal (ULN) or if total bilirubin is > 1.5 x ULN, the direct bilirubin must be =< ULN =< 28 days prior to registration
  • Alkaline phosphatase =< 3 x ULN =< 28 days prior to registration
  • Aspartate transaminase (AST) =< 3 x ULN
  • Creatinine =< 2 x ULN =< 28 days prior to registration
  • Negative pregnancy test done =< 7 days prior to registration, for women of childbearing potential only
  • Provide informed written consent
  • Willing to travel to a radioimmunotherapy site for Zevalin, if necessary
  • Willing to return to the enrolling institution for follow-up (during the Active Monitoring Phase of the study); Note: during the Active Monitoring Phase of a study (i.e., active treatment and observation), participants must be willing to return to the consenting institution for follow-up
  • Willing to provide blood samples at baseline for correlative research purposes and tissue for central pathology review
  • < 25% bone marrow involvement of cellular marrow with lymphoma as determined by bilateral bone marrow aspirate and biopsy; NOTE: the percent involvement should be estimated by the hematopathologist using all of the biopsy material
  • Has insurance coverage or is willing to pay for protocol therapy (rituximab x 4 or Zevalin x 1)

Who cannot join

  • 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
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  • 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
  • Major surgery other than diagnostic surgery =< 4 weeks prior to registration
  • Any evidence of myelodysplastic syndrome or marrow chromosomal changes suggesting myelodysplasia (-7, -5 etc)
  • Corticosteroid therapy at the time the patient enters the protocol; NOTE: patients using prednisone or its equivalent for adrenal failure or using =< 10 mg of prednisone/day for other benign causes are accepted
  • Follicular grades IIIA or IIIB are not eligible
  • Marrow cellularity =< 15% (as determined on all bone marrow samples)
  • Seropositive for or active viral infection with hepatitis B virus (HBV):
  • Hepatitis B surface antigen (HBsAg) positive
  • HBsAg negative, anti-hepatitis B surface antibody (HBs) positive and/or anti-hepatitis B core antibody (HBc) positive and detectable viral deoxyribonucleic acid (DNA)
  • Notes:
  • Subjects who are HBsAg negative, anti-HBs positive, and/or anti-HBc positive, but viral DNA negative are eligible
  • Subjects who are seropositive because of HBV vaccination are eligible (HBV surface antibody positive, HBV core antibody negative, and HBV surface antigen negative)
  • Active infection with hepatitis C virus (HCV)

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Mayo Clinic in Rochester

    Rochester, Minnesota, 55905

Other trials in United States

About this study

Official title: The Asymptomatic Follicular Lymphoma (AFL) Trial: A Phase III Study of Single-Agent Rituximab Immunotherapy Versus Zevalin Radioimmunotherapy for Patients With New, Untreated Follicular Lymphoma Who Are Candidates for Observation

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.

Read the detailed description

PRIMARY OBJECTIVE:

  1. Test the hypothesis that a single dose of Zevalin (yttrium Y-90 ibritumomab tiuxetan) rituximab immunotherapy (RIT) will increase the complete remission (CR) rate over that achieved with standard rituximab in patients with untreated asymptomatic follicular lymphoma (FL).

SECONDARY OBJECTIVES:

  1. Test the hypothesis that Zevalin RIT will improve progression-free survival. II. Test the hypothesis that Zevalin RIT will improve time to next (any) therapy and time to next chemotherapy.

CORRELATIVE RESEARCH OBJECTIVES:

  1. Study the incidence of exon 2 B-cell leukemia/lymphoma 2 protein (bcl2) mutations in patients with asymptomatic follicular lymphoma (AFL).

II. Measure regulatory T cells (Tregs) and tissue monocytes in on-study FL tumor tissue.

III. Measure serum cytokines and vitamin D at on study and month 6. IV. Evaluate beta-2 microglobulin plus lactate dehydrogenase (LDH) score as a prognostic factor.

  1. Measure absolute lymphocyte count (ALC), absolute monocyte count (AMC), and ALC/AMC ratio at on study and after treatment.

VI. Compare quality of life as measured by the Functional Assessment of Cancer Therapy (FACT)-Lymphoma (Lym) between arms.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM A: Patients receive rituximab intravenously (IV) on days 1, 8, 15, and 22.

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

After completion of study treatment, patients are followed up at 3, 6, 9, 12, 18, 24, 30, 36, 48, and 60 months and then every 12 months for 5 years.

Being tested
Quality-of-Life Assessment, Rituximab, Yttrium Y-90 Ibritumomab Tiuxetan

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Quality-of-Life AssessmentOther

    Also called Quality of Life Assessment

    Ancillary studies

  • RituximabBiological

    Also called ABP 798, BI 695500, C2B8 Monoclonal Antibody, Chimeric Anti-CD20 Antibody

    Given IV

  • Yttrium Y-90 Ibritumomab TiuxetanRadiation

    Also called IDEC-Y2B8, IDEC-Y2B8 monoclonal antibody, Y 90 Ibritumomab Tiuxetan, Y 90 Zevalin

    Given IV

Study groups in NCT02320292
Study groupRoleWhat they receive
Arm A (rituximab)Active comparatorPatients receive rituximab IV on days 1, 8, 15, and 22.
Receives: Other: Quality-of-Life Assessment; Biological: Rituximab
Arm B (rituximab, yttrium Y-90 ibritumomab tiuxetan)ExperimentalPatients receive rituximab IV on days 1 and 8 and yttrium Y-90 ibritumomab tiuxetan over 10 minutes on day 8.
Receives: Other: Quality-of-Life Assessment; Biological: Rituximab; Radiation: Yttrium Y-90 Ibritumomab Tiuxetan

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: 6 months

Secondary outcomes (4)

  1. Progression-free Survival (PFS)

    The distribution of progression-free survival time will be estimated using the method of Kaplan-Meier within each arm and compared between the arms using a logrank test. The progression-free survival rates at 3 years and 5 years will be estimated in each arm.

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

  2. Time to Any Therapy (TTNT)

    The distribution of time to any therapy will be estimated using the method of Kaplan-Meier within each arm and compared between the arms using a log-rank test. The percentage of patients free of any therapy at 3 years and 5 years will be estimated in each arm.

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

  3. Time to Chemotherapy (TTC)

    The distribution of time to chemotherapy will be estimated using the method of Kaplan-Meier within each arm and compared between the arms using a log-rank test. The percentage of patients free of chemotherapy at 3 years and 5 years will be estimated in each arm.

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

  4. Incidence of Adverse Events

    Assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0. The maximum grade for each type of adverse event will be recorded for each patient, and frequency tables will be reviewed to determine patterns. Additionally, the relationship of the adverse event(s) to the study treatment will be taken into consideration. Rates of individual adverse events (grade 3 and higher) will be compared between arms using a Fisher's exact test.

    Measured: Up to 5 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted19 Dec 2014 (estimated)
  2. Study start11 Feb 2015
  3. Primary completion28 Feb 2021
  4. Study completion9 Nov 2023

Why it stopped: drug supply issues

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
20 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02320292
Sponsor's protocol ID
LS138D
Other IDs
NCI-2014-02476, LS138D, 14-003066
Status last verified
Nov 2023
First submitted
15 Dec 2014
Last updated
9 Jul 2025
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Quality-of-Life Assessment, Rituximab and Yttrium Y-90 Ibritumomab Tiuxetan in people with Ann Arbor Stage I Grade 1 Follicular Lymphoma and Ann Arbor Stage I Grade 2 Follicular Lymphoma, run by Mayo Clinic at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 31 inclusion and 27 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 9 Jul 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 18 Jul 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Complete Response (CR) Rate at the 6-month Disease Assessment (time frame: 6 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02320292.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Jul 2025.

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