A Phase I Trial Combining IDEC-Y2B8 And High-Dose Beam Chemotherapy With Hematopoietic Progenitor Cell Transplant In Patients With Relapsed Or Refractory B-Cell Non-Hodgkin's Lymphoma
17 Years
N/A
Both
Lymphoma
Trial Information
A Phase I Trial Combining IDEC-Y2B8 And High-Dose Beam Chemotherapy With Hematopoietic Progenitor Cell Transplant In Patients With Relapsed Or Refractory B-Cell Non-Hodgkin's Lymphoma
OBJECTIVES:
- Determine the maximum tolerated dose of yttrium Y 90 ibritumomab tiuxetan, in terms of
absorbed radiation to critical organs, when administered with high-dose chemotherapy
followed by autologous peripheral blood stem cell transplantation in patients with
relapsed or refractory B-cell non-Hodgkin's lymphoma.
- Determine whether the residual radioactivity detected at the time of stem cell
reinfusion affects the reinfused cells and delays engraftment in patients treated with
this regimen.
- Determine the duration of response and survival of patients treated with this regimen.
OUTLINE: This is a dose-escalation study of yttrium Y 90 ibritumomab tiuxetan (IDEC-Y2B8).
- Radioimmunotherapy: Patients receive rituximab IV followed by indium In 111 ibritumomab
tiuxetan (for imaging) IV over 10 minutes on day -22. Patients then receive rituximab
IV and IDEC-Y2B8 IV over 10 minutes on day -14.
Cohorts of 3-6 patients receive escalating doses of IDEC-Y2B8 until the maximum tolerated
dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 3
of 6 patients experience dose-limiting toxicity.
- High-dose conditioning regimen: Patients receive BEAM chemotherapy comprising
carmustine IV over 2 hours on day -6, etoposide IV over 2 hours twice daily and
cytarabine IV over 1 hour twice daily on days -5 to -2, and melphalan IV over 1 hour on
day -1.
- Autologous stem cell transplantation: Autologous peripheral blood stem cells are
reinfused on day 0. Patients receive filgrastim (G-CSF) subcutaneously daily beginning
on day 0 and continuing until blood counts recover.
Patients are followed at 30 days, 3 and 6 months, and then annually for 5 years.
PROJECTED ACCRUAL: A maximum of 42 patients will be accrued for this study.
Inclusion Criteria
DISEASE CHARACTERISTICS:
- Histologically confirmed B-cell non-Hodgkin's lymphoma
- Relapsed or refractory disease
- CD20-positive disease
- Must have received at least 1 prior treatment regimen
- Complete remission with prior conventional salvage chemotherapy is allowed
- No more than 25% lymphoma in bone marrow
- No circulating malignant cells on blood smear
- No CNS involvement by lymphoma
- No HIV- or AIDS-related lymphoma
PATIENT CHARACTERISTICS:
Age
- Over 17
Performance status
- ECOG 0-2
Life expectancy
- At least 3 months
Hematopoietic
- Platelet count at least 100,000/mm^3
- Absolute neutrophil count at least 1,500/mm^3
Hepatic
- Transaminases less than 2 times normal
Renal
- Creatinine clearance greater than 50 mL/min
Cardiovascular
- LVEF at least 45%
Pulmonary
- Corrected DLCO at least 70% of predicted
- FEV_1 or FVC greater than 60%
Other
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
- No active infection
- No serious nonmalignant disease or other condition that would preclude study
participation
PRIOR CONCURRENT THERAPY:
Biologic therapy
- More than 4 weeks since prior rituximab and recovered
- No other prior murine antibodies
- No prior stem cell transplantation
- No prior radioimmunoconjugate therapy
Chemotherapy
- See Disease Characteristics
- More than 6 weeks since prior nitrosoureas or mitomycin and recovered
Endocrine therapy
- No concurrent systemic corticosteroids
Radiotherapy
- Recovered from prior radiotherapy
- No prior external beam irradiation to more than 25% of the active bone marrow
Surgery
- More than 4 weeks since prior major surgery and recovered
Other
- More than 3 weeks since prior anticancer therapy
Type of Study:
Interventional
Study Design:
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Determine the maximum tolerated dose of absorbed radiation to critical organs delivered with this combination of study treatments
Outcome Description:
Dose limiting toxicities observed during and up to 30 days after the last study treatment resulting in the determination of the maximum tolerated dose of absorbed radiation to critical organs delivered by Y2B8 in combination with high-dose BEAM chemotherapy with autologous mobilized peripheral blood progenitor cell transplant
Outcome Time Frame:
From first study treatment until 30 days after last study treatment.
Safety Issue:
Yes
Principal Investigator
Jane N. Winter, MD
Investigator Role:
Study Chair
Investigator Affiliation:
Robert H. Lurie Cancer Center
Authority:
United States: Federal Government
Study ID:
NU 99H11
NCT ID:
NCT00058292
Start Date:
April 2000
Completion Date:
March 2009
Related Keywords:
- Lymphoma
- recurrent grade 1 follicular lymphoma
- recurrent grade 2 follicular lymphoma
- recurrent grade 3 follicular lymphoma
- recurrent adult diffuse large cell lymphoma
- recurrent adult diffuse mixed cell lymphoma
- recurrent adult Burkitt lymphoma
- recurrent adult immunoblastic large cell lymphoma
- recurrent mantle cell lymphoma
- recurrent adult lymphoblastic lymphoma
- recurrent adult diffuse small cleaved cell lymphoma
- recurrent marginal zone lymphoma
- recurrent small lymphocytic lymphoma
- extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue
- nodal marginal zone B-cell lymphoma
- splenic marginal zone lymphoma
- Lymphoma
- Lymphoma, Non-Hodgkin
- Lymphoma, B-Cell
Name | Location |
|---|---|
| Mayo Clinic Cancer Center | Rochester, Minnesota 55905 |
| Robert H. Lurie Comprehensive Cancer Center at Northwestern University | Chicago, Illinois 60611 |
| Hematology-Oncology Associates of Illinois | Chicago, Illinois 60611-2998 |
