Lymphoma
Conditions
Keywords
recurrent adult diffuse large cell lymphoma, recurrent adult immunoblastic large cell lymphoma, anaplastic large cell lymphoma
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.
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.
Interventions
BIOLOGICALrituximab
DRUGcytarabine
to be used for CNS prophylaxis
to be used as CNS prophylaxis
RADIATIONyttrium Y 90 ibritumomab tiuxetan
Sponsors
Beth Israel Deaconess Medical Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Standard Phase 2
Eligibility
Sex/Gender
ALL
Age
18 Years to 120 Years
Healthy volunteers
No
Inclusion 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| Best Response | 12 months | This data is the best overall response achieved by patients by the 12 month period. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Event Free Survival | 12 months | the median time point at which a participants experienced and event or toxicity or progression |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Yttrium Y 90 Ibritumomab Tiuxetan and Rituximab Yttrium Y 90 Ibritumomab Tiuxetan and Rituximab | 25 |
| Total | 25 |
Baseline characteristics
| Characteristic | Yttrium Y 90 Ibritumomab Tiuxetan and Rituximab |
|---|---|
| Age, Continuous | 70 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 23 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Region of Enrollment United States | 25 participants |
| Sex: Female, Male Female | 11 Participants |
| Sex: Female, Male Male | 14 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 25 |
| other Total, other adverse events | 17 / 25 |
| serious Total, serious adverse events | 0 / 25 |
Outcome results
Primary
Best Response
This data is the best overall response achieved by patients by the 12 month period.
Time frame: 12 months
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Yttrium Y 90 Ibritumomab Tiuxetan and Rituximab | Best Response | CR | 8 Participants |
| Yttrium Y 90 Ibritumomab Tiuxetan and Rituximab | Best Response | PR | 1 Participants |
| Yttrium Y 90 Ibritumomab Tiuxetan and Rituximab | Best Response | SD | 1 Participants |
| Yttrium Y 90 Ibritumomab Tiuxetan and Rituximab | Best Response | PD | 15 Participants |
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
Time frame: 12 weeks
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Yttrium Y 90 Ibritumomab Tiuxetan and Rituximab | Response Rate = Complete and Partial Response at 12 Weeks. | SD | 2 participants |
| Yttrium Y 90 Ibritumomab Tiuxetan and Rituximab | Response Rate = Complete and Partial Response at 12 Weeks. | PD | 15 participants |
| Yttrium Y 90 Ibritumomab Tiuxetan and Rituximab | Response Rate = Complete and Partial Response at 12 Weeks. | CR | 5 participants |
| Yttrium Y 90 Ibritumomab Tiuxetan and Rituximab | Response Rate = Complete and Partial Response at 12 Weeks. | PR | 3 participants |
Secondary
Event Free Survival
the median time point at which a participants experienced and event or toxicity or progression
Time frame: 12 months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Yttrium Y 90 Ibritumomab Tiuxetan and Rituximab | Event Free Survival | 2.5 months |