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Y 90 Ibritumomab Tiuxetan &Rituximab Relapsed or Refractory Diffuse Large B-Cell Non-Hodgkin's Lymphoma

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ClinicalTrials.gov Identifier: NCT00073957
Recruitment Status : Completed
First Posted : December 11, 2003
Results First Posted : January 23, 2018
Last Update Posted : January 23, 2018
Sponsor:
Information provided by (Responsible Party):
Robin Joyce, Beth Israel Deaconess Medical Center

Brief Summary:

RATIONALE: Monoclonal antibodies, such as yttrium Y 90 ibritumomab tiuxetan and rituximab, can locate cancer cells and either kill them or deliver radioactive cancer-killing substances to them without harming normal cells. Combining yttrium Y 90 ibritumomab tiuxetan with rituximab may kill more cancer cells.

PURPOSE: Phase II trial to study the effectiveness of combining yttrium Y 90 Ibritumomab tiuxetan with rituximab in treating patients who have relapsed or refractory diffuse large B-cell non-Hodgkin's lymphoma.


Condition or disease Intervention/treatment Phase
Lymphoma Biological: rituximab Drug: cytarabine Drug: liposomal cytarabine Radiation: yttrium Y 90 ibritumomab tiuxetan Phase 2

Detailed Description:

OBJECTIVES:

  • Determine the best overall response in patients with relapsed or refractory diffuse large B-cell non-Hodgkin's lymphoma treated with yttrium Y 90 ibritumomab tiuxetan and rituximab.
  • Determine the event-free survival of patients treated with this regimen.
  • Determine the toxicity of this regimen in these patients.

OUTLINE: This is an open-label, multicenter study.

  • Radioimmunotherapy: Patients receive indium In 111 ibritumomab tiuxetan IV over 10 minutes on day 1 (for imaging only); yttrium Y 90 ibritumomab tiuxetan IV over 10 minutes on day 8; and rituximab IV over 3-4 hours on days 1, 8, 15, 22, 29, and 36.
  • CNS ( central nervous system)prophylaxis: Patients receive CNS prophylaxis comprising intrathecal (IT) methotrexate or IT cytarabine on days 15, 22, 29, and 36 OR IT cytarabine (liposomal) on days 15 and 29.
  • Maintenance rituximab: Patients are assessed for response at week 14. Beginning at month 6, patients with stable or responding disease receive maintenance therapy comprising rituximab IV over 3-4 hours once weekly for 4 weeks. Maintenance therapy repeats every 6 months for 2 years (total of 4 courses) in the absence of disease progression or unacceptable toxicity.

Patients are followed every 3 months for 2 years and then every 6 months for 2 years.

PROJECTED ACCRUAL: A total of 40 patients will be accrued for this study within 2 years.


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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 25 participants
Intervention Model: Single Group Assignment
Intervention Model Description: Standard Phase 2
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Zevalin And Rituxan For The Treatment Of Relapsed Or Refractory Diffuse Large B-Cell Non-Hodgkin's Lymphoma
Actual Study Start Date : December 2003
Actual Primary Completion Date : January 1, 2012
Actual Study Completion Date : January 1, 2012


Arm Intervention/treatment
Experimental: Y-90 Ibritumomab Tiuxetan
Yttrium Y 90 Ibritumomab Tiuxetan and Rituximab and central nervous system prophylaxis with Cytarabine or liposomal cytarabine
Biological: rituximab
Other Name: Rituxan

Drug: cytarabine
to be used for CNS prophylaxis
Other Name: cytosine arabinoside

Drug: liposomal cytarabine
to be used as CNS prophylaxis
Other Name: Depocyte

Radiation: yttrium Y 90 ibritumomab tiuxetan
Other Name: Zevalin




Primary Outcome Measures :
  1. Response Rate = Complete and Partial Response at 12 Weeks. [ Time Frame: 12 weeks ]
    Definition Nodal Masses Spleen, Liver Bone Marrow CR Disappearance of all evidence of disease Partial response Regression and no new sites ≥ 50% decrease in sum of the perpendicular dimension of up to 6 largest dominant masses; no increase in size of other nodes Stable disease Failure to attain CR/PR or Progressive disease or Relapsed disease : the appearance of any new lesion or the (a) FDG-avid or PET positive prior to therapy; PET positive at prior sites of disease and no new sites on CT or PET Any new lesion or increase by ≥ 50% of previously involved sites from nadir Appearance of a new lesion(s) > 1.5 cm in any axis, ≥ 50% increase in SPD of more than one node, or ≥ 50% increase in longest diameter of a previously identified node > 1 cm in short axis > 50% increase from nadir in the SPD of any previous lesions New or recurrent involvement Lesions PET positive if FDG-avid lymphoma or PET positive prior to therapy

  2. Best Response [ Time Frame: 12 months ]
    This data is the best overall response achieved by patients by the 12 month period.


Secondary Outcome Measures :
  1. Event Free Survival [ Time Frame: 12 months ]
    the median time point at which a participants experienced and event or toxicity or progression



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 120 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Histologically confirmed diffuse large B-cell non-Hodgkin's lymphoma, including any of the following:

    • B-cell diffuse large cell variant
    • Immunoblastic
    • Mediastinal (thymic) large cell
    • T-cell/histiocyte-rich
    • Anaplastic large B-cell
    • Intravascular large B-cell
    • Lymphomatoid granulomatosis
  • Relapsed or refractory disease after at least 1 prior chemotherapy regimen and requires further treatment

    • Relapsed disease, defined as the following:

      • Appearance of any new lesion OR increase of at least 50% in the size of a previously involved site
      • 50% increase in greatest diameter of any previously identified node greater than 1 cm in the short axis OR in the sum of the perpendicular diameter (SPD) of more than 1 node
    • Progressive disease, defined as the following:

      • 50% increase from nadir in the SPD of any previously identified abnormal node
      • Appearance of any new lesion during or at the end of therapy
  • CD20-positive disease by immunohistochemistry
  • Bidimensionally measurable disease

    • At least 1 lesion at least 2.0 cm by CT scan
  • Less than 25% bone marrow involvement by lymphoma
  • No transformed lymphoma from indolent to aggressive
  • No HIV- or AIDS-related lymphoma
  • No hypocellular bone marrow
  • No marked reduction in bone marrow precursors of 1 or more cell lines (e.g., granulocytic, megakaryocytic, or erythroid)
  • No CNS lymphoma
  • Ineligible for myeloablative therapy OR refused transplantation
  • Ineligible for any other open yttrium Y 90 ibritumomab tiuxetan investigational protocols

PATIENT CHARACTERISTICS:

Age

  • 18 and over

Performance status

  • WHO 0-2

Life expectancy

  • At least 3 months

Hematopoietic

  • Absolute neutrophil count at least 1,500/mm^3
  • Lymphocyte count no greater than 5,000/mm^3 (for patients with small lymphocytic lymphoma)
  • Platelet count at least 100,000/mm^3

Hepatic

  • Bilirubin no greater than 2.0 mg/dL

Renal

  • Creatinine no greater than 2.0 mg/dL

Other

  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception during and for 1 year after study participation
  • No concurrent serious nonmalignant disease or infection that would preclude study participation
  • No human antimurine antibody reactivity

PRIOR CONCURRENT THERAPY:

Biologic therapy

  • See Disease Characteristics
  • No prior autologous bone marrow transplantation
  • No prior peripheral blood stem cell rescue
  • No prior failed stem cell collection
  • Prior rituximab within the past 90 days allowed provided patient has fludeoxyglucose-avid disease that is also indium In 111 ibritumomab tiuxetan-avid disease in at least 1 lesion
  • More than 2 weeks since prior filgrastim (G-CSF) or sargramostim (GM-CSF)

Chemotherapy

  • See Disease Characteristics

Endocrine therapy

  • Not specified

Radiotherapy

  • No prior radioimmunotherapy
  • No prior external beam radiotherapy (involved field or regional) to more than 25% of active bone marrow

Surgery

  • More than 4 weeks since prior major surgery (except diagnostic surgery)

Other

  • Recovered from all prior therapy
  • More than 4 weeks since prior therapy for lymphoma
  • More than 8 weeks since prior phase II investigational drugs
  • No other concurrent antineoplastic therapy

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00073957


Locations
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United States, Massachusetts
Beth Israel Deaconess Medical Center
Boston, Massachusetts, United States, 02215
United States, Vermont
Fletcher Allen Health Care - Medical Center Campus
Burlington, Vermont, United States, 05401
Sponsors and Collaborators
Beth Israel Deaconess Medical Center
Investigators
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Study Chair: Robin Joyce, MD Beth Israel Deaconess Medical Center

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Responsible Party: Robin Joyce, Assistant Professor of Medicine, Beth Israel Deaconess Medical Center
ClinicalTrials.gov Identifier: NCT00073957     History of Changes
Other Study ID Numbers: 2003P000182
CDR0000341437 ( Registry Identifier: PDQ (Physician Data Query) )
First Posted: December 11, 2003    Key Record Dates
Results First Posted: January 23, 2018
Last Update Posted: January 23, 2018
Last Verified: December 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No

Keywords provided by Robin Joyce, Beth Israel Deaconess Medical Center:
recurrent adult diffuse large cell lymphoma
recurrent adult immunoblastic large cell lymphoma
anaplastic large cell lymphoma

Additional relevant MeSH terms:
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Lymphoma
Lymphoma, Non-Hodgkin
Lymphoma, B-Cell
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Rituximab
Cytarabine
Antibodies, Monoclonal
Antineoplastic Agents, Immunological
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antiviral Agents
Anti-Infective Agents
Immunosuppressive Agents