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 - Full Text View

Sponsored by:	Swiss Group for Clinical Cancer Research
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00392691

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: filgrastim Drug: ibritumomab tiuxetan Drug: melphalan Drug: rituximab Drug: vinorelbine ditartrate Drug: yttrium Y 90 ibritumomab tiuxetan Procedure: autologous hematopoietic stem cell transplantation Procedure: peripheral blood stem cell transplantation	Phase I

MedlinePlus related topics: Cancer Lymphoma

Drug Information available for: Filgrastim Melphalan Vinorelbine Vinorelbine tartrate Rituximab Ibritumomab tiuxetan Melphalan hydrochloride Sarcolysin

U.S. FDA Resources

Study Type:	Interventional
Study Design:	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

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Dose-limiting toxicity of high-dose melphalan in combination with yttrium Y 90 ibritumomab tiuxetan [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Toxicity [ Designated as safety issue: Yes ]
Event occurrence up to 100 days after transplantation [ Designated as safety issue: No ]
Complete remission 100 days after transplantation [ Designated as safety issue: No ]
Successful stem cell harvest [ Designated as safety issue: No ]

Estimated Enrollment:	24
Study Start Date:	October 2006

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
Centre Hospitalier Universitaire Vaudois	Recruiting
Lausanne, Switzerland, CH-1011
Contact: Nicolas Ketterer, MD 41-21-314-0169
Inselspital Bern	Recruiting
Bern, Switzerland, CH-3010
Contact: Thomas Pabst, MD 41-31-632-2111
Kantonspital Aarau	Recruiting
Aarau, Switzerland, CH-5001
Contact: Mario Bargetzi, MD 41-62-838-6050 mario.bargetzi@ksa.ch
Ospedale Civico	Recruiting
Lugano, Switzerland, CH-6903
Contact: Michele Ghielmini, MD 41-91-811-6111
Kantonsspital Liestal	Recruiting
Bern, Switzerland, CH-3008
Contact: Michele Voegeli, MD 41-61-925-2716
Kantonsspital - St. Gallen	Recruiting
St. Gallen, Switzerland, CH-9007
Contact: Felicitas Hitz, MD 41-71-494-1066

Sponsors and Collaborators

Swiss Group for Clinical Cancer Research

Investigators

Study Chair:

Michele Voegeli, MD

Kantonsspital Liestal

More Information

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

Study ID Numbers:	CDR0000511915, SWS-SAKK-37/05, EU-20648, SPRI-SWS-SAKK-37/05
Study First Received:	October 25, 2006
Last Updated:	December 2, 2008
ClinicalTrials.gov Identifier:	NCT00392691
Health Authority:	Unspecified

Keywords provided by National Cancer Institute (NCI):

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
Waldenstrom macroglobulinemia

Study placed in the following topic categories:

Melphalan
Lymphoma, Mantle-Cell
Lymphoma, Follicular
Lymphoma, small cleaved-cell, diffuse
Vinblastine
Lymphoma, B-Cell, Marginal Zone
Lymphoma, large-cell, immunoblastic
Antibodies, Monoclonal
Lymphoma, B-Cell
Lymphoma, large-cell
Burkitt's lymphoma
Leukemia, Lymphocytic, Chronic, B-Cell
Lymphoma, Large-Cell, Immunoblastic
Waldenstrom macroglobulinemia
Lymphoma

Immunoglobulins
Chronic lymphocytic leukemia
Lymphoma, Large B-Cell, Diffuse
Immunoproliferative Disorders
Rituximab
Leukemia, B-cell, chronic
Lymphoblastic lymphoma
Mantle cell lymphoma
Recurrence
Lymphatic Diseases
Antibodies
Waldenstrom Macroglobulinemia
Vinorelbine
Burkitt Lymphoma
B-cell lymphomas

Additional relevant MeSH terms:

Neoplasms by Histologic Type
Immune System Diseases
Immunologic Factors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Mitosis Modulators
Physiological Effects of Drugs
Antimitotic Agents
Immunosuppressive Agents

Pharmacologic Actions
Neoplasms
Therapeutic Uses
Tubulin Modulators
Myeloablative Agonists
Antineoplastic Agents, Alkylating
Antirheumatic Agents
Antineoplastic Agents, Phytogenic
Alkylating Agents

ClinicalTrials.gov processed this record on January 14, 2009