Neoplasms

Blood and Lymph Conditions

Immune System Diseases

All Conditions

Rare Diseases

Lymphoma

Lymphoma, Follicular

Neoplasms by Histologic Type

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Lymphoma, Non-Hodgkin

Lymphosarcoma

Follicular Lymphoma

All Drugs and Chemicals

Antineoplastic Agents

Antirheumatic Agents

Antibodies

Antibodies, Monoclonal

Rituximab

Immunomodulating Agents

Immunoglobulins

Antineoplastic Agents, Immunological

Immunoglobulins, Intravenous

Immunologic Factors

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

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

Quality-of-Life Assessment

Yttrium Y-90 Ibritumomab Tiuxetan

Thomas E. Witzig, M.D.

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.

PRIMARY OBJECTIVE:

I. 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:

I. 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:

I. 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.

V. 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.

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

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

Will be evaluated in each arm independently and may also be compared between the two arms. Values may be investigated with respect to response (CR vs. less than CR) chi-square tests. Relationship with time to event measures (PFS, TTNT, TTC) will be evaluated using Kaplan-Meier methods and log-rank statistics (categorical measures).

Will be evaluated in each arm independently and may also be compared between the two arms. Values may be investigated with respect to response (CR vs. less than CR) chi-square tests. Relationship with time to event measures (PFS, TTNT, TTC) will be evaluated using Kaplan-Meier methods and log-rank statistics (categorical measures). For values collected at more than one time point, changes over time will be evaluated using paired-t-tests.

Each cytokine will be evaluated in reference to normal controls and levels will be categorized as normal, elevated, or suppressed. Will be evaluated in each arm independently and may also be compared between the two arms. Values may be investigated with respect to response (CR vs. less than CR) chi-square tests. Relationship with time to event measures (PFS, TTNT, TTC) will be evaluated using Kaplan-Meier methods and log-rank statistics (categorical measures). For values collected at more than one time point, changes over time will be evaluated using paired-t-tests.

Vitamin D level will be categorized as normal (sufficient) vs. abnormal (insufficient). Will be evaluated in each arm independently and may also be compared between the two arms. Values may be investigated with respect to response (CR vs. less than CR) chi-square tests. Relationship with time to event measures (PFS, TTNT, TTC) will be evaluated using Kaplan-Meier methods and log-rank statistics (categorical measures). For values collected at more than one time point, changes over time will be evaluated using paired-t-tests.

Will be categorized at baseline as low risk (both factors =\< 150% ULN), intermediate risk (one factor =\< 150% IULN and the other factor \> 150% ULN), or high risk (both factors \> 150% IULN). The prognostic value of B2m plus LDH score in relation to PFS will be evaluated using Kaplan-Meier methods and log-rank statistics. Will be evaluated in each arm independently and may also be compared between the two arms.

Both the absolute and relative change will be summarized for each measure. Will be evaluated in each arm independently and may also be compared between the two arms. Values may be investigated with respect to response (CR vs. less than CR) chi-square tests. Relationship with time to event measures (PFS, TTNT, TTC) will be evaluated using Kaplan-Meier methods and log-rank statistics (categorical measures). For values collected at more than one time point, changes over time will be evaluated using paired-t-tests.

As assessed by Functional Assessment of Cancer Therapy (FACT). Mean FACT will be graphically presented by arm using a mean plot with standard deviation error bars including all available data with patients according to the randomized treatment assignment. Baseline characteristics will be compared between arms within the subject of patients who provide QOL data at one or more time points using t-tests for continuous variables and chi-squared tests for categorical variables.

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.

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.

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.

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.

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.

National Cancer Institute (NCI)

Mayo Clinic

Arm A (Rituximab)

Yttrium Y-90 Ibritumomab Tiuxetan: Given IV

Arm B (Rituximab, Yttrium Y-90 Ibritumomab Tiuxetan)

Patients receive rituximab IV on days 1, 8, 15, and 22.\> \> Quality-of-Life Assessment: Ancillary studies\>

\> Rituximab: Given IV

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

\> Quality-of-Life Assessment: Ancillary studies\>

\> Rituximab: Given IV\>

\> Yttrium Y-90 Ibritumomab Tiuxetan: Given IV

Total

Age, Continuous

18-29

30-39

40-49

50-59

60-69

Age, Customized

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

Normal

Abnormal

Beta-2 Microglobulin

< 3 months

3-12 months

Time from Diagnosis to Registration

Lactate Dehydrongenase

Follicular Lymp Grade 1

Follicular Lymp Grade 2

An indolent (slow-growing) type of non-Hodgkin lymphoma marked by enlarged lymph nodes and a mix of large cells and small cells that have cleaved (u-shaped) nuclei. Grade 1 is better, Grade 2 is worse.

NHL Type

Low Risk

Intermediate Risk

High Risk

FLIPI2 score

Dr. Thomas E Witzig

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

Progression-free Survival (PFS)

Time to Any Therapy (TTNT)

Time to Chemotherapy (TTC)

Incidence of Adverse Events

Incidence of Exon 2 bcl2 Mutations

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

Change in Serum Cytokines

Change in Vitamin D

Beta-2 Microglobulin (B2m) Plus LDH Score

Change in Absolute Lymphocyte Count (ALC)

Change in Absolute Monocyte Count (AMC) Ratio

Change in ALC/AMC Ratio

Quality of Life (QOL)

Overall Study

Lenalidomide

Angiogenesis Inhibitors

Growth Inhibitors

Patients receive lenalidomide PO QD on days 1-21. Treatment with lenalidomide repeats every 28 days for 12 courses in the absence of disease progression or unacceptable toxicity. Patients also receive rituximab IV on days 1, 8, 15, and 22 and in weeks 13, 21, 29, and 37 in the absence of disease progression or unacceptable toxicity.

Laboratory Biomarker Analysis

Peter Martin

This phase II trial studies how well lenalidomide and rituximab work in treating patients with previously untreated stage II, stage III, or stage IV follicular non-Hodgkin lymphoma. Biological therapies, such as lenalidomide, may stimulate or suppress the immune system in different ways and stop cancer cells from growing. Monoclonal antibodies, such as rituximab, may interfere with the ability of cancer cells to grow and spread. Giving lenalidomide together with rituximab may kill more cancer cells.

PRIMARY OBJECTIVES:

I. To determine the response rate (overall and complete) to lenalidomide + rituximab in follicular non-Hodgkin lymphoma (NHL) patients who have received no prior systemic therapy.

II. To determine the time to progression after lenalidomide + rituximab in previously untreated patients with cluster of differentiation (CD)20+ follicular NHL.

SECONDARY OBJECTIVES:

I. To determine the toxicity profile of lenalidomide + rituximab therapy in previously untreated patients with CD20+ follicular NHL.

II. To establish whether the therapeutic effects of lenalidomide + rituximab combination are sufficiently promising to warrant evaluation in a subsequent randomized trial (in comparison to rituximab alone).

III. To correlate fragment crystallizable gamma (Fcg) receptor polymorphism profiling with response to lenalidomide + rituximab in previously untreated patients with follicular NHL.

IV. To determine the impact of lenalidomide on immune parameters in patients with previously untreated follicular lymphoma.

V. To determine the impact of lenalidomide on angiogenic parameters in patients with previously untreated follicular lymphoma.

VI. To correlate lymphoma-associated macrophages (LAM) and forkhead box P3 (FOXP3), granzyme B (GzB), CD10, multiple myeloma oncogene 1 (MUM1), and B-cell lymphoma 2 (BCL2) expression with response to rituximab + lenalidomide in previously untreated patients with follicular lymphoma.

VII. Determine whether immune gene signatures previously identified as prognostic factors in follicular lymphoma (FL) can be applied to paraffin-embedded tissues in rituximab treated patients; evaluate micro ribonucleic acid (RNA) signatures associated with these gene signatures and outcome; to validate immunohistochemical markers associated with outcome in FL (CD68 LAMs, FOXP3, CD10, BCL6, FOXP1, MUM1); and investigate whether markers of angiogenesis may be of value in prognosis of FL.

OUTLINE:

Patients receive lenalidomide orally (PO) once daily (QD) on days 1-21. Treatment with lenalidomide repeats every 28 days for 12 courses in the absence of disease progression or unacceptable toxicity. Patients also receive rituximab intravenously (IV) on days 1, 8, 15, and 22 and on weeks 13, 21, 29, and 37 in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 4 months for 2 years and then every 6 months for up to 8 years.

Lenalidomide and Rituximab in Treating Patients With Previously Untreated Stage II, Stage III, or Stage IV Follicular Non-Hodgkin Lymphoma

A Phase II Trial of Lenalidomide (Revlimid (TM), CC-5013) (NSC #703813) Plus Rituximab in Previously Untreated Follicular Non-Hodgkin Lymphoma (NHL)

Response is assessed by investigator according to International Working Group (IWG) criteria. Complete response requires disappearance of all evidence of disease.

Data will be summarized using frequency tables.

Kaplan-Meier method will be used. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.

Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.

Treatment (Lenalidomide, Rituximab)

Patients receive oral lenalidomide (20mg) once daily on days 1-21. Treatment with lenalidomide repeats every 28 days for 12 courses in the absence of disease progression or unacceptable toxicity. Patients also receive rituximab (375mg/m\^2) IV in weeks 1, 2, 3, 4, 12, 20, 28, and 36 in the absence of disease progression or unacceptable toxicity.\> \> rituximab: Given IV\>

\> lenalidomide: Given orally

United States

Region of Enrollment

Follicular Lymphoma International Prognostic Index (FLIPI) (abstracted from Solal-Céligny et al., Blood, 2004. 104(5): p. 1258-1265)\>

\> Factors (1 point for each variable present): \>

* Age \> 60y\>
* Ann Arbor Stage III-IV (range I-IV, with III and IV indicating highest risk)\>
* Hemoglobin level \< 12 g/dL\>
* Lactate dehydrogenase (LDH) level \> upper limit of normal (ULN)\>
* \>= 4 nodal sites of disease\>

Risk category (factors):\>

* Low risk (0 or 1)\>
* Intermediate risk (2)\>
* High risk (\> 3)

Follicular Lymphoma International Prognostic Index (FLIPI)

Includes one participant did not start protocol treatment after baseline and was dropped from all analyses.

Peter Martin, M.D.

Number of Participants Who Achieved a Complete Response

Grade 1-2 Fatigue

Grade 1-2 Diarrhea

Grade 1-2 Rash

Grade 1-2 Febrile neutropenia

Grade 3-4 Neutropenia

Grade 3-4 Lymphopenia

Grade 3-4 Thrombocytopenia

Grade 3-4 Infection

Grade 3-4 Rash

Patients receive oral lenalidomide (20mg) once daily on days 1-21. Treatment with lenalidomide repeats every 28 days for 12 courses in the absence of disease progression or unacceptable toxicity. Patients also receive rituximab (375mg/m\^2) IV in weeks 1, 2, 3, 4, 12, 20, 28, and 36 in the absence of disease progression or unacceptable toxicity.\> \>\>

\>

\>\> rituximab: Given IV\>

\>\>

\>

\>\> lenalidomide: Given orally

Toxicity of Study Treatment, Assessed by the NCI Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0

2 Years PFS

3 Years PFS

4 Years PFS

5 Years PFS

Patients receive lenalidomide PO QD on days 1-21. Treatment with lenalidomide repeats every 28 days for 12 courses in the absence of disease progression or unacceptable toxicity. Patients also receive rituximab IV on days 1, 8, 15, and 22 and in weeks 13, 21, 29, and 37 in the absence of disease progression or unacceptable toxicity.\>

\> Laboratory Biomarker Analysis: Correlative studies\>

\> Lenalidomide: Given PO\>

\> Rituximab: Given IV

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Rituximab With or Without Yttrium Y-90 Ibritumomab Tiuxetan in Treating Patients With Untreated Follicular Lymphoma	NCT02320292	Ann Arbor Stage... Ann Arbor Stage... Ann Arbor Stage... Ann Arbor Stage... Ann Arbor Stage... Ann Arbor Stage... Ann Arbor Stage... Ann Arbor Stage... Ann Arbor Stage... Ann Arbor Stage...	Quality-of-Life... Rituximab Yttrium Y-90 Ib...	18 Years -	Mayo Clinic
Lenalidomide and Rituximab in Treating Patients With Previously Untreated Stage II, Stage III, or Stage IV Follicular Non-Hodgkin Lymphoma	NCT01145495	Ann Arbor Stage... Ann Arbor Stage... Ann Arbor Stage... Ann Arbor Stage... Ann Arbor Stage... Ann Arbor Stage... Ann Arbor Stage... Ann Arbor Stage... Ann Arbor Stage... Ann Arbor Stage... Ann Arbor Stage... Ann Arbor Stage...	Laboratory Biom... Lenalidomide Rituximab	18 Years -	National Cancer Institute (NCI)
Rituximab With or Without Yttrium Y-90 Ibritumomab Tiuxetan in Treating Patients With Untreated Follicular Lymphoma	NCT02320292	Ann Arbor Stage... Ann Arbor Stage... Ann Arbor Stage... Ann Arbor Stage... Ann Arbor Stage... Ann Arbor Stage... Ann Arbor Stage... Ann Arbor Stage... Ann Arbor Stage... Ann Arbor Stage...	Quality-of-Life... Rituximab Yttrium Y-90 Ib...	18 Years -	Mayo Clinic
Lenalidomide and Rituximab in Treating Patients With Previously Untreated Stage II, Stage III, or Stage IV Follicular Non-Hodgkin Lymphoma	NCT01145495	Ann Arbor Stage... Ann Arbor Stage... Ann Arbor Stage... Ann Arbor Stage... Ann Arbor Stage... Ann Arbor Stage... Ann Arbor Stage... Ann Arbor Stage... Ann Arbor Stage... Ann Arbor Stage... Ann Arbor Stage... Ann Arbor Stage...	Laboratory Biom... Lenalidomide Rituximab	18 Years -	National Cancer Institute (NCI)

Spots Global Cancer Trial Database for ann arbor stage ii grade 2 contiguous follicular lymphoma