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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier:
NCT00058422
First received: April 7, 2003
Last updated: April 23, 2014
Last verified: April 2014
  Purpose

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.


Condition Intervention Phase
Lymphoma
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
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Study of R-CHOP and Ibritumomab Tiuxetan (Zevalin) for Elderly Patients With Previously Untreated Diffuse Large B-Cell Lymphoma

Resource links provided by NLM:


Further study details as provided by Memorial Sloan-Kettering Cancer Center:

Primary Outcome Measures:
  • Overall survival [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Progression-free survival [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Event-free survival [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • incidence of adverse experiences [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Enrollment: 65
Study Start Date: February 2003
Estimated Study Completion Date: February 2015
Estimated Primary Completion Date: February 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: R-CHOP and Ibritumomab Tiuxetan (Zevalin)

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

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.

  Eligibility

Ages Eligible for Study:   60 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00058422

Locations
United States, New York
Memorial Sloan-Kettering Cancer Center
New York, New York, United States, 10021
United States, Texas
M. D. Anderson Cancer Center at University of Texas
Houston, Texas, United States, 77030-4009
Sponsors and Collaborators
Memorial Sloan-Kettering Cancer Center
Investigators
Study Chair: Paul A. Hamlin, MD Memorial Sloan-Kettering Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier: NCT00058422     History of Changes
Other Study ID Numbers: 02-090, MSKCC-02090
Study First Received: April 7, 2003
Last Updated: April 23, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Memorial Sloan-Kettering Cancer Center:
noncontiguous stage II adult diffuse large cell lymphoma
stage III adult diffuse large cell lymphoma
stage IV adult diffuse large cell lymphoma

Additional relevant MeSH terms:
Lymphoma, B-Cell
Lymphoma
Lymphoma, Large B-Cell, Diffuse
Lymphoma, Non-Hodgkin
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Cyclophosphamide
Rituximab
Liposomal doxorubicin
Doxorubicin
Prednisone
Vincristine
Antibodies, Monoclonal
Darbepoetin alfa
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Antibiotics, Antineoplastic

ClinicalTrials.gov processed this record on October 01, 2014