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
This study is ongoing, but not recruiting participants.
Sponsor:
Swiss Group for Clinical Cancer Research
Information provided by (Responsible Party):
Swiss Group for Clinical Cancer Research
ClinicalTrials.gov Identifier:
NCT00392691
First received: October 25, 2006
Last updated: November 27, 2012
Last verified: November 2012
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Purpose
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 | Intervention | Phase |
|---|---|---|
|
Lymphoma |
Drug: ibritumomab tiuxetan Drug: rituximab Drug: melphalan Drug: vinorelbine tartrate / G-CSF Procedure: autologous hematopoietic stem cell harvesting and transplantation |
Phase 1 |
| Study Type: | Interventional |
| Study Design: | Endpoint Classification: Safety Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment |
| 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 |
Resource links provided by NLM:
Drug Information available for:
Melphalan
Melphalan hydrochloride
Vinorelbine
Vinorelbine tartrate
Granulocyte colony-stimulating factor
Rituximab
Ibritumomab tiuxetan
U.S. FDA Resources
Further study details as provided by Swiss Group for Clinical Cancer Research:
Primary Outcome Measures:
- Dose-limiting toxicity of high-dose melphalan in combination with yttrium Y 90 ibritumomab tiuxetan [ Time Frame: within 8 weeks after application of melphalan ] [ Designated as safety issue: Yes ]
Secondary Outcome Measures:
- Toxicity [ Time Frame: 100 days (+/- 5 days) after reinfusion of stem cells ] [ Designated as safety issue: Yes ]
- Event occurrence up to 100 days after transplantation [ Time Frame: up to 100 days after transplantation ] [ Designated as safety issue: No ]
- Complete remission 100 days after transplantation [ Time Frame: 100 days after transplantation ] [ Designated as safety issue: No ]
| Estimated Enrollment: | 24 |
| Study Start Date: | October 2006 |
| Estimated Study Completion Date: | April 2013 |
| Estimated Primary Completion Date: | December 2012 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
| 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
Drug: rituximab
250 mg/m2
Other Name: MabThera
Drug: melphalan
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. |
Detailed Description:
OBJECTIVES:
- 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.
Eligibility| Ages Eligible for Study: | 65 Years and older |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
Criteria
DISEASE CHARACTERISTICS:
- Histologically confirmed non-Hodgkin's lymphoma of any type
- CD20-positive disease
- Achieved partial or complete response to salvage treatment for relapse or refractory disease within the past 10 weeks
- Must have an indication for autologous stem cell transplantation
- Bone marrow infiltration < 25%
- No evidence of CNS involvement
PATIENT CHARACTERISTICS:
- WHO performance status 0-1
- Bilirubin ≤ 2 times upper limit of normal (ULN)
- Alkaline phosphatase ≤ 2 times ULN
- AST ≤ 2 times ULN
- Creatinine clearance > 50 mL/min
No clinically significant cardiac disease, including any of the following:
- Unstable angina pectoris
- Significant arrhythmia
- Myocardial infarction within the past 3 months
- LVEF > 50%
- No clinically significant urinary tract obstruction
- No clinically significant pulmonary disease
- No serious underlying medical condition that would preclude study participation
- No other malignancy within the past 5 years except nonmelanoma skin cancer or adequately treated in situ cervical cancer
PRIOR CONCURRENT THERAPY:
- See Disease Characteristics
- At least 30 days since prior participation in another clinical trial
- No prior stem cell transplantation
- No prior radiolabeled antibodies, including for induction of disease remission
- No prior radiotherapy to ≥ 25% of the bone marrow
- No concurrent radiotherapy
- No other concurrent anticancer drugs
- No other concurrent investigational drugs
Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00392691
Locations
| Switzerland | |
| Kantonsspital Aarau | |
| Aarau, Switzerland, CH-5001 | |
| Saint Claraspital AG | |
| Basel, Switzerland, 4016 | |
| Universitaetsspital-Basel | |
| Basel, Switzerland, CH-4031 | |
| Istituto Oncologico della Svizzera Italiana - Ospedale Regionale Bellinzona e Valli | |
| Bellinzona, Switzerland, 6500 | |
| Kantonsspital Liestal | |
| Bern, Switzerland, CH-3008 | |
| Inselspital Bern | |
| Bern, Switzerland, 3010 | |
| Kantonsspital Bruderholz | |
| 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 | |
Sponsors and Collaborators
Swiss Group for Clinical Cancer Research
Investigators
| 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 |
More Information
No publications provided
| Responsible Party: | Swiss Group for Clinical Cancer Research |
| ClinicalTrials.gov Identifier: | NCT00392691 History of Changes |
| Other Study ID Numbers: | SAKK 37/05, SWS-SAKK-37/05, EU-20648, SPRI-SWS-SAKK-37/05, CDR0000511915 |
| Study First Received: | October 25, 2006 |
| Last Updated: | November 27, 2012 |
| Health Authority: | Switzerland: Swissmedic |
Keywords provided by Swiss Group for Clinical Cancer Research:
|
recurrent adult Burkitt lymphoma recurrent adult diffuse large cell lymphoma recurrent adult diffuse mixed cell lymphoma recurrent adult diffuse small cleaved cell lymphoma recurrent adult immunoblastic large cell lymphoma recurrent adult lymphoblastic lymphoma recurrent grade 1 follicular lymphoma recurrent grade 2 follicular lymphoma |
recurrent grade 3 follicular lymphoma recurrent mantle 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 Waldenström macroglobulinemia |
Additional relevant MeSH terms:
|
Lymphoma Lymphoma, Non-Hodgkin Neoplasms by Histologic Type Neoplasms Lymphoproliferative Disorders Lymphatic Diseases Immunoproliferative Disorders Immune System Diseases Melphalan Vinorelbine Rituximab Vinblastine Antibodies, Monoclonal Myeloablative Agonists |
Immunosuppressive Agents Immunologic Factors Physiological Effects of Drugs Pharmacologic Actions Antineoplastic Agents Therapeutic Uses Antineoplastic Agents, Alkylating Alkylating Agents Molecular Mechanisms of Pharmacological Action Antineoplastic Agents, Phytogenic Tubulin Modulators Antimitotic Agents Mitosis Modulators Antirheumatic Agents |
ClinicalTrials.gov processed this record on May 16, 2013