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

Lymphoma Clinical Trial

Official title:

Zevalin And Rituxan For The Treatment Of Relapsed Or Refractory Diffuse Large B-Cell Non-Hodgkin's Lymphoma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00073957
• Other study ID #: 2003P000182
• Secondary ID: CDR0000341437
• Status: Completed
• Phase: Phase 2
• First received: December 10, 2003
• Last updated: December 21, 2017
• Start date: December 2003
• Est. completion date: January 1, 2012

Study information

• Verified date: December 2017
• Source: Beth Israel Deaconess Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 25
• Est. completion date: January 1, 2012
• Est. primary completion date: January 1, 2012
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 120 Years

Eligibility

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

Related Conditions & MeSH terms

• Lymphoma
• Lymphoma, B-Cell
• Lymphoma, Non-Hodgkin

Intervention

Biological:
• rituximab

Drug:
• cytarabine
to be used for CNS prophylaxis
• liposomal cytarabine
to be used as CNS prophylaxis

Radiation:
• yttrium Y 90 ibritumomab tiuxetan

Locations

Country	Name	City	State
United States	Beth Israel Deaconess Medical Center	Boston	Massachusetts
United States	Fletcher Allen Health Care - Medical Center Campus	Burlington	Vermont

Sponsors (1)

Lead Sponsor	Collaborator
Beth Israel Deaconess Medical Center

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Response Rate = Complete and Partial Response at 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	12 weeks
Primary	Best Response	This data is the best overall response achieved by patients by the 12 month period.	12 months
Secondary	Event Free Survival	the median time point at which a participants experienced and event or toxicity or progression	12 months