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

Primary Purpose

Lymphoma

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
darbepoetin alfa
filgrastim
rituximab
cyclophosphamide
doxorubicin hydrochloride
prednisone
vincristine sulfate
indium In 111 ibritumomab tiuxetan
yttrium Y 90 ibritumomab tiuxetan
Sponsored by
Memorial Sloan Kettering Cancer Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Lymphoma focused on measuring noncontiguous stage II adult diffuse large cell lymphoma, stage III adult diffuse large cell lymphoma, stage IV adult diffuse large cell lymphoma

Eligibility Criteria

60 Years - 120 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Memorial Sloan Kettering Cancer Center
  • M. D. Anderson Cancer Center at University of Texas

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

R-CHOP and Ibritumomab Tiuxetan (Zevalin)

Arm Description

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.

Outcomes

Primary Outcome Measures

Overall Survival
Progression-free Survival
Event-free Survival
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.

Secondary Outcome Measures

Conversion Rate to Complete Remission

Full Information

First Posted
April 7, 2003
Last Updated
October 19, 2020
Sponsor
Memorial Sloan Kettering Cancer Center
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT00058422
Brief Title
Rituximab and Combination Chemotherapy Combined With Yttrium Y 90 Ibritumomab Tiuxetan in Treating Older Patients With Previously Untreated B-Cell Lymphoma
Official Title
A Phase II Study of R-CHOP and Ibritumomab Tiuxetan (Zevalin) for Elderly Patients With Previously Untreated Diffuse Large B-Cell Lymphoma
Study Type
Interventional

2. Study Status

Record Verification Date
October 2020
Overall Recruitment Status
Completed
Study Start Date
February 10, 2003 (Actual)
Primary Completion Date
November 14, 2019 (Actual)
Study Completion Date
November 14, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Memorial Sloan Kettering Cancer Center
Collaborators
National Cancer Institute (NCI)

4. Oversight

5. Study Description

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.
Detailed Description
OBJECTIVES: Determine the progression-free and overall survival of patients age 60 and over with previously untreated diffuse large B-cell lymphoma treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) combined with yttrium Y 90 ibritumomab tiuxetan. 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. Determine the predictive value of detecting minimal residual disease by molecular techniques for future relapse/recurrence in patients treated with this regimen. Determine the response rate of patients treated with this regimen. Determine the red blood cell transfusion requirements, change in hemoglobin from baseline, and incidence of anemia with prophylactic darbepoetin alfa support in patients treated with this regimen. Determine the conversion rate to complete remission in patients treated with ibritumomab tiuxetan who achieve a partial remission post-R-CHOP. Determine the effect of darbepoetin alfa on the quality of life of these patients. OUTLINE: This is an open-label, nonrandomized study. 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. PROJECTED ACCRUAL: A total of 65 patients will be accrued for this study.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Lymphoma
Keywords
noncontiguous stage II adult diffuse large cell lymphoma, stage III adult diffuse large cell lymphoma, stage IV adult diffuse large cell lymphoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
65 (Actual)

8. Arms, Groups, and Interventions

Arm Title
R-CHOP and Ibritumomab Tiuxetan (Zevalin)
Arm Type
Experimental
Arm Description
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.
Intervention Type
Biological
Intervention Name(s)
darbepoetin alfa
Intervention Type
Biological
Intervention Name(s)
filgrastim
Intervention Type
Biological
Intervention Name(s)
rituximab
Intervention Type
Drug
Intervention Name(s)
cyclophosphamide
Intervention Type
Drug
Intervention Name(s)
doxorubicin hydrochloride
Intervention Type
Drug
Intervention Name(s)
prednisone
Intervention Type
Drug
Intervention Name(s)
vincristine sulfate
Intervention Type
Radiation
Intervention Name(s)
indium In 111 ibritumomab tiuxetan
Intervention Type
Radiation
Intervention Name(s)
yttrium Y 90 ibritumomab tiuxetan
Primary Outcome Measure Information:
Title
Overall Survival
Time Frame
2 years
Title
Progression-free Survival
Time Frame
2 years
Title
Event-free Survival
Time Frame
2 years
Title
Incidence of Adverse Experiences
Description
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.
Time Frame
2 years
Secondary Outcome Measure Information:
Title
Conversion Rate to Complete Remission
Time Frame
2 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
60 Years
Maximum Age & Unit of Time
120 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Paul A. Hamlin, MD
Organizational Affiliation
Memorial Sloan Kettering Cancer Center
Official's Role
Study Chair
Facility Information:
Facility Name
Memorial Sloan Kettering Cancer Center
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States
Facility Name
M. D. Anderson Cancer Center at University of Texas
City
Houston
State/Province
Texas
ZIP/Postal Code
77030-4009
Country
United States

12. IPD Sharing Statement

Links:
URL
https://www.mskcc.org/
Description
Memorial Sloan Kettering Cancer Center

Learn more about this trial

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

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