Melphalan, Yttrium Y 90 Ibritumomab Tiuxetan, and Rituximab Followed by Autologous Stem Cell Transplant in Treating Older Patients With Non-Hodgkin's Lymphoma That Has Relapsed or Not Responded to Previous Treatment
|ClinicalTrials.gov Identifier: NCT00392691|
Recruitment Status : Completed
First Posted : October 26, 2006
Last Update Posted : July 10, 2013
RATIONALE: Giving chemotherapy drugs, such as melphalan, before an autologous stem cell transplant helps stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Also, monoclonal antibodies, such as yttrium Y 90 ibritumomab tiuxetan and rituximab, can find cancer cells and carry cancer-killing substances to them without harming normal cells. Chemotherapy and monoclonal antibody therapy also prepares the patient's bone marrow for the stem cell transplant. Giving colony-stimulating factors, such as G-CSF, and vinorelbine helps stem cells move from the bone marrow to the blood so they can be collected and stored. The stem cells are returned to the patient to replace the blood-forming cells that were destroyed by the chemotherapy and monoclonal antibody therapy.
PURPOSE: This phase I trial is studying the side effects and best dose of melphalan when given together with yttrium Y 90 ibritumomab tiuxetan and rituximab followed by autologous stem cell transplant in treating older patients with non-Hodgkin's lymphoma that has relapsed or not responded to previous treatment.
|Condition or disease||Intervention/treatment||Phase|
|Lymphoma||Drug: ibritumomab tiuxetan Drug: rituximab Drug: melphalan Drug: vinorelbine tartrate / G-CSF Procedure: autologous hematopoietic stem cell harvesting and transplantation||Phase 1|
- Determine the maximum tolerated dose of high-dose melphalan when given together with yttrium Y 90 ibritumomab tiuxetan and rituximab as a conditioning regimen followed by vinorelbine ditartrate- and filgrastim (G-CSF)-mobilized autologous stem cell transplantation in elderly patients with relapsed or refractory CD20-positive non-Hodgkin's lymphoma.
- Evaluate the feasibility and safety of this regimen in these patients.
- Determine the feasibility of stem cell mobilization with vinorelbine ditartrate in patients treated with this regimen.
OUTLINE: This is a multicenter, dose-escalation study of high-dose melphalan.
- Stem cell harvest and mobilization: Patients receive vinorelbine ditartrate IV on day -36 and filgrastim (G-CSF) subcutaneously (SC) twice daily on days -33 to -29. Patients undergo peripheral blood stem cell harvest on days -29 to -26.
- Radioimmunotherapy: Patients receive rituximab IV. Within 4 hours after completion of rituximab, patients receive indium In 111 ibritumomab tiuxetan (imaging dose) IV over 10 minutes on day -25. Patients undergo assessment of biodistribution, imaging, and dosimetry on days -25, -22, and optionally on day -20. Patients with acceptable biodistribution of indium In 111 ibritumomab tiuxetan receive rituximab IV followed by yttrium Y 90 ibritumomab tiuxetan (therapeutic dose) IV over 10 minutes on day -18.
- High-dose chemotherapy: Patients receive high-dose melphalan IV on day -1. Cohorts of 3-6 patients receive escalating doses of high-dose melphalan until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity.
- Autologous stem cell transplantation (ASCT): Patients undergo ASCT on day 0. Patients receive G-CSF SC beginning on day 5 and continuing until blood counts recover.
After completion of study treatment, patients are followed for 100 days.
PROJECTED ACCRUAL: A total of 24 patients will be accrued for this study.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||20 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Ibritumomab Tiuxetan and High-Dose Melphalan as Conditioning Regimen Before Autologous Stem Cell Transplantation for Elderly Patients With Lymphoma in Relapse or Resistant to Chemotherapy. A Multicenter Phase I Trial|
|Study Start Date :||October 2006|
|Actual Primary Completion Date :||December 2012|
|Actual Study Completion Date :||May 2013|
|Experimental: Zevalin, Rituximab, Melphalan||
Drug: ibritumomab tiuxetan
185 MBq (5mCi) of 111In-Zevalin will be used for radioimaging. and the dose is 14.8 MBq/kg (0.4 mCi/kg) total body weight of 90Y-Zevalin (max. 1184 MBq or 32 mCi at patients > 80kg) for imaging.
Other Name: ZEVALIN
Other Name: MabThera
Other Name: Alkeran
Drug: vinorelbine tartrate / G-CSF
on day 1: 35 mg/m2 day 4-8 (longer if required) G-CSF 5 μg/kg s.c. morning and 5 μg/kg s.c. evening for at least 5 days
Other Name: Navelbine
Procedure: autologous hematopoietic stem cell harvesting and transplantation
Optimal mobilization usually takes place on day 8. A minimum of 2.5x106 CD34+ cells/kg should be collected (optimal 5x106 CD34+ cells/kg). If not enough CD34+ cells can be collected on day 8, it is recommended to continue with G-CSF until a sufficient collection (a minimum of 2.5x106 CD34+ cells/kg) can be obtained.
Stem cells will be reinfused approximately 24 hours after the melphalan administration. The infusion will be performed with a minimum of 2.5x106 CD34+ cells/kg body weight according to local guidelines. G-CSF (5 μg/kg/d) will be given from day 5 and continued until neutrophils > 0.5x109/l for at least 2 consecutive days.
- Dose-limiting toxicity of high-dose melphalan in combination with yttrium Y 90 ibritumomab tiuxetan [ Time Frame: within 8 weeks after application of melphalan ]
- Toxicity [ Time Frame: 100 days (+/- 5 days) after reinfusion of stem cells ]
- Event occurrence up to 100 days after transplantation [ Time Frame: up to 100 days after transplantation ]
- Complete remission 100 days after transplantation [ Time Frame: 100 days after transplantation ]
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00392691
|Aarau, Switzerland, CH-5001|
|Saint Claraspital AG|
|Basel, Switzerland, 4016|
|Basel, Switzerland, CH-4031|
|Istituto Oncologico della Svizzera Italiana - Ospedale Regionale Bellinzona e Valli|
|Bellinzona, Switzerland, 6500|
|Bern, Switzerland, 3010|
|Bern, Switzerland, CH-3008|
|Bruderholz, Switzerland, 4101|
|Hopital Cantonal Universitaire de Geneve|
|Geneva, Switzerland, CH-1211|
|Centre Hospitalier Universitaire Vaudois|
|Lausanne, Switzerland, CH-1011|
|Kantonsspital - St. Gallen|
|St. Gallen, Switzerland, CH-9007|
|Study Chair:||Michele Voegeli, MD||Kantonsspital Liestal|
|Study Chair:||Michele Ghielmini, Prof||IOSI, Ospedale San Giovanni|
|Study Chair:||Angelika Bischof Delaloye, Prof||Faculté de biologie et de médecine de l' Université de Lausanne|