Rituximab and Combination Chemotherapy Combined With Yttrium Y 90 Ibritumomab Tiuxetan in Treating Older Patients With Previously Untreated B-Cell Lymphoma

NCT00058422 | Completed Phase 2 Results

• 2 other identifiers: 02-090MSKCC-02090
• Study Type: interventional
• Target: 65
• Locations: 1 country
• Sites: 2

Brief Summary

RATIONALE: Monoclonal antibodies such as rituximab and yttrium Y 90 ibritumomab tiuxetan can locate cancer cells and either kill them or deliver radioactive cancer-killing substances to them without harming normal cells. Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Combining rituximab and combination chemotherapy with yttrium Y 90 ibritumomab tiuxetan may kill more cancer cells. PURPOSE: Phase II trial to study the effectiveness of combining rituximab and combination chemotherapy with yttrium Y 90 ibritumomab tiuxetan in treating older patients who have B-cell lymphoma that has not been previously treated.

Conditions

Lymphoma

Keywords

noncontiguous stage II adult diffuse large cell lymphoma; stage III adult diffuse large cell lymphoma; stage IV adult diffuse large cell lymphoma

Outcome Measures

Primary Outcomes (4)

• Overall Survival

  2 years

• Progression-free Survival

  2 years

• Event-free Survival

  2 years

• Incidence of Adverse Experiences

  Determine the incidence of adverse experiences, hematologic toxicity (WBC, hemoglobin, and platelet nadirs; and transfusion requirements), cardiac toxicity (incidence of left ventricular dysfunction and cardiomyopathy by echocardiography), and the development of human antimouse antibody/human anti-chimeric antibody in patients treated with this regimen.

  2 years

Secondary Outcomes (1)

• Conversion Rate to Complete Remission

  2 years

Study Arms (1)

R-CHOP and Ibritumomab Tiuxetan (Zevalin)

EXPERIMENTAL

Chemotherapy: Patients receive rituximab IV over 2-5 hours, cyclophosphamide IV, doxorubicin IV, and vincristine IV on day 1; oral prednisone on days 1-5 or 2-6; and filgrastim (G-CSF) subcutaneously (SC) on days 7-15. Patients also receive darbepoetin alfa SC on day 1. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Radioimmunotherapy: Patients receive rituximab IV over 3-5 hours and indium In 111 ibritumomab tiuxetan (IDEC-In2B8) IV over 10 minutes on day 0. Patients undergo gamma camera imaging at 2-24 hours and 48-72 hours after the injection of IDEC-In2B8 to observe the flow of ibritumomab tiuxetan. If the flow is deemed safe, then patients receive yttrium Y 90 ibritumomab tiuxetan IV over 10 minutes on day 7. Quality of life is assessed at baseline, before course 5 of chemotherapy, before radioimmunotherapy, and at 3 months. Patients are followed every 3 months for 1 year and then every 6 months for 4 years.

Biological: darbepoetin alfa; Biological: filgrastim; Biological: rituximab; Drug: cyclophosphamide; Drug: doxorubicin hydrochloride; Drug: prednisone; Drug: vincristine sulfate; Radiation: indium In 111 ibritumomab tiuxetan; Radiation: yttrium Y 90 ibritumomab tiuxetan

Interventions

darbepoetin alfa BIOLOGICAL

R-CHOP and Ibritumomab Tiuxetan (Zevalin)

filgrastim BIOLOGICAL

R-CHOP and Ibritumomab Tiuxetan (Zevalin)

rituximab BIOLOGICAL

R-CHOP and Ibritumomab Tiuxetan (Zevalin)

cyclophosphamide DRUG

R-CHOP and Ibritumomab Tiuxetan (Zevalin)

doxorubicin hydrochloride DRUG

R-CHOP and Ibritumomab Tiuxetan (Zevalin)

prednisone DRUG

R-CHOP and Ibritumomab Tiuxetan (Zevalin)

vincristine sulfate DRUG

R-CHOP and Ibritumomab Tiuxetan (Zevalin)

indium In 111 ibritumomab tiuxetan RADIATION

R-CHOP and Ibritumomab Tiuxetan (Zevalin)

yttrium Y 90 ibritumomab tiuxetan RADIATION

R-CHOP and Ibritumomab Tiuxetan (Zevalin)

Eligibility Criteria

• Age: 60 Years - 120 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

DISEASE CHARACTERISTICS: * Histologically confirmed diffuse large B-cell lymphoma, including any of the following subtypes: * Centroblastic * Immunoblastic * T-cell/histiocyte-rich * Lymphomatoid granulomatosis type * Anaplastic large B-cell * Plasmablastic * Mediastinal * Intravascular large B-cell lymphoma * Previously untreated * High-intermediate or high-risk disease, defined by an age-adjusted international prognostic index score of 2 or 3 (with 1 point each assigned for a ECOG greater than 1/Karnofsky less than 80%, lactate dehydrogenase greater than normal, and stage III or IV) * Lymphomas with discordant histology and a diffuse large B-cell component are eligible * Must have an initial diagnostic specimen that is CD20+ * At least Ann Arbor stage II disease * No confinement of disease to an involved-field radiotherapy port (stage I or limited stage II disease) * Bidimensionally measurable disease with at least 1 lymph node at least 2.0 cm by 2.0 cm by physical examination, CT scan, or positron-emission tomography * Bone marrow cellularity greater than 15% * No known brain or leptomeningeal metastases * No primary effusion lymphomas PATIENT CHARACTERISTICS: Age * 60 and over\* NOTE: \*Patients 60 to 65 years of age must be deemed ineligible for autologous stem cell transplantation Performance status * Karnofsky 50-100% Life expectancy * Not specified Hematopoietic * Not specified Hepatic * Bilirubin no greater than 2.0 mg/dL (except for Gilbert's disease) Renal * Creatinine no greater than 1.5 mg/dL\* OR * Creatinine clearance greater than 50 mL/min\* NOTE: \*Patients not meeting either criterion but who have renal insufficiency directly related to lymphomatous involvement of the kidneys or renal collecting system are allowed Cardiovascular * Cardiac ejection fraction at least 50% by echocardiogram * No acute myocardial infarction within the past 3 months * No uncontrolled hypertension * No New York Heart Association class III or IV congestive heart failure * No unstable angina pectoris Other * Not pregnant or nursing * Fertile patients must use effective contraception * HIV negative * B12 and folate greater than the lower limit of normal * Transferrin saturation at least 15% * Ferritin greater than 10 µg/L * At least 6 weeks since prior RBC donation * No active seizure disorder * Prior seizure disorder allowed if free of antiseizure medication and evidence of seizure activity for the past 5 years * No concurrent uncontrolled medical problems that would preclude administration of chemotherapy or radioimmunotherapy * No other concurrent malignancy treated with chemotherapy or radiotherapy except adequately treated basal cell or squamous cell skin cancer or carcinoma in situ of the cervix PRIOR CONCURRENT THERAPY: Biologic therapy * At least 4 weeks since prior RBC transfusion * No prior biologic therapy * No other concurrent biologic therapy Chemotherapy * No prior chemotherapy (one course of R-CHOP allowed) * No other concurrent standard or investigational chemotherapy Endocrine therapy * No more than 7 consecutive days of prior steroids (premedication allowed for prior intravenous contrast allergy) * No other concurrent corticosteroids Radiotherapy * No prior radiotherapy Surgery * Not specified

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Memorial Sloan Kettering Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (2)

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

M. D. Anderson Cancer Center at University of Texas

Houston, Texas, 77030-4009, United States

Location

Related Links

• Memorial Sloan Kettering Cancer Center

MeSH Terms

Conditions

Lymphoma; Lymphoma, Large B-Cell, Diffuse

Interventions

Darbepoetin alfa; Filgrastim; Rituximab; Cyclophosphamide; Doxorubicin; Prednisone; Vincristine; Indium; ibritumomab tiuxetan

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Lymphoma, B-Cell; Lymphoma, Non-Hodgkin

Intervention Hierarchy (Ancestors)

Erythropoietin; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Proteins; Amino Acids, Peptides, and Proteins; Granulocyte Colony-Stimulating Factor; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Biological Factors; Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Polycyclic Compounds; Aminoglycosides; Glycosides; Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines; Metals, Heavy; Elements; Inorganic Chemicals; Metals

Results Point of Contact

• Title: Paul A. Hamlin, M.D.
• Organization: Memorial Sloan Kettering Cancer Center

hamlinp@mskcc.org

646-608-1667

Study Officials

• Paul A. Hamlin, MD

  Memorial Sloan Kettering Cancer Center

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 7, 2003
• First Posted: April 9, 2003
• Study Start: February 10, 2003
• Primary Completion: November 14, 2019
• Study Completion: November 14, 2019
• Last Updated: November 12, 2020
• Results First Posted: November 12, 2020

Record last verified: 2020-10

Locations

US (2)