Rituximab With or Without Yttrium Y-90 Ibritumomab Tiuxetan in Treating Patients With Untreated Follicular Lymphoma
Condition: 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
MeSH terms: Lymphoma; Lymphoma, Follicular
Intervention: Quality-of-Life Assessment; Rituximab; Yttrium Y-90 Ibritumomab Tiuxetan
Intervention description: Ancillary studies; Given IV; Given IV
Intervention MeSH terms: Rituximab; Antineoplastic Agents, Immunological; Antibodies; Immunoglobulins; Antibodies, Monoclonal
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 20.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

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.
    

Eligibility criteria:

        Inclusion Criteria:

          -  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

               -  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)

        Exclusion Criteria:

          -  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

          -  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)