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

• Sponsor: Beth Israel Deaconess Medical Center (Other)
• Overall Status: Completed
• CT.gov ID: NCT00073957
• Collaborator: (none)
• Enrollment: 25
• Locations: 2
• Arm: 1
• Actual Duration (Months): 97
• Patients Per Site: 12.5
• Patients Per Site Per Month: 0.1

Study Details

Study Description

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 25 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Intervention Model Description: Standard Phase 2Standard 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: Dec 1, 2003
• Actual Primary Completion Date: Jan 1, 2012
• Actual Study Completion Date: Jan 1, 2012

Arms and Interventions

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 Names: Rituxan ; Drug: cytarabine; to be used for CNS prophylaxis; Other Names: cytosine arabinoside ; Drug: liposomal cytarabine; to be used as CNS prophylaxis; Other Names: Depocyte ; Radiation: yttrium Y 90 ibritumomab tiuxetan; Other Names: Zevalin

Outcome Measures

Primary Outcome Measures

1. Response Rate = Complete and Partial Response at 12 Weeks. [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 [12 months]

   This data is the best overall response achieved by patients by the 12 month period.

Secondary Outcome Measures

1. Event Free Survival [12 months]

   the median time point at which a participants experienced and event or toxicity or progression

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 120 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Beth Israel Deaconess Medical Center	Boston	Massachusetts	United States	02215
2	Fletcher Allen Health Care - Medical Center Campus	Burlington	Vermont	United States	05401

Sponsors and Collaborators

• Beth Israel Deaconess Medical Center

Investigators

• Study Chair: Robin Joyce, MD, Beth Israel Deaconess Medical Center

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Robin Joyce, Assistant Professor of Medicine, Beth Israel Deaconess Medical Center
• ClinicalTrials.gov Identifier: NCT00073957
• Other Study ID Numbers: 2003P000182; CDR0000341437
• First Posted: Dec 11, 2003
• Last Update Posted: Jan 23, 2018
• Last Verified: Dec 1, 2017

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• 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, Assistant Professor of Medicine, 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: Lymphoma; Lymphoma, Non-Hodgkin; Lymphoma, B-Cell; Cytarabine; Rituximab

Study Results

Participant Flow

Arm/Group Title	Yttrium Y 90 Ibritumomab Tiuxetan and Rituximab
Arm/Group Description	Yttrium Y 90 Ibritumomab Tiuxetan and Rituximab
Period Title: Overall Study
STARTED	25
COMPLETED	25
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Yttrium Y 90 Ibritumomab Tiuxetan and Rituximab
Arm/Group Description	Yttrium Y 90 Ibritumomab Tiuxetan and Rituximab
Overall Participants	25
Age (years) [Mean (Full Range) ]
Mean (Full Range) [years]	70
Sex: Female, Male (Count of Participants)
Female	11 44%
Male	14 56%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	2 8%
Not Hispanic or Latino	23 92%
Unknown or Not Reported	0 0%
Region of Enrollment (participants) [Number]
United States	25 100%

Outcome Measures

1. Primary Outcome

Title	Response Rate = Complete and Partial Response at 12 Weeks.
Description	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
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Yttrium Y 90 Ibritumomab Tiuxetan and Rituximab
Arm/Group Description	Yttrium Y 90 Ibritumomab Tiuxetan and Rituximab
Measure Participants	25
CR	5 20%
PR	3 12%
SD	2 8%
PD	15 60%

2. Primary Outcome

Title	Best Response
Description	This data is the best overall response achieved by patients by the 12 month period.
Time Frame	12 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Yttrium Y 90 Ibritumomab Tiuxetan and Rituximab
Arm/Group Description	Y 90 Ibritumomab Tiuxetan and Rituximab
Measure Participants	25
CR	8 32%
PR	1 4%
SD	1 4%
PD	15 60%

3. Secondary Outcome

Title	Event Free Survival
Description	the median time point at which a participants experienced and event or toxicity or progression
Time Frame	12 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Yttrium Y 90 Ibritumomab
Arm/Group Description	Yttrium Y 90 Ibritumomab Tiuxetan and Rituximab
Measure Participants	25
Median (Full Range) [months]	2.5

Adverse Events

Arm/Group Title	Yttrium Y 90 Ibritumomab Tiuxetan and Rituximab
Arm/Group Description	Yttrium Y 90 Ibritumomab Tiuxetan and Rituximab
All Cause Mortality
	Yttrium Y 90 Ibritumomab Tiuxetan and Rituximab
	Affected / at Risk (%)	# Events
Total	0/25 (0%)
Serious Adverse Events
	Yttrium Y 90 Ibritumomab Tiuxetan and Rituximab
	Affected / at Risk (%)	# Events
Total	0/25 (0%)
Other (Not Including Serious) Adverse Events
	Yttrium Y 90 Ibritumomab Tiuxetan and Rituximab
	Affected / at Risk (%)	# Events
Total	17/25 (68%)
Investigations
Thrombocytopenia	17/25 (68%)	17

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.