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 has been completed.
Sponsor:
Information provided by (Responsible Party):
Swiss Group for Clinical Cancer Research
ClinicalTrials.gov Identifier:
NCT00392691
First received: October 25, 2006
Last updated: July 9, 2013
Last verified: July 2013
  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:


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 ]

Enrollment: 20
Study Start Date: October 2006
Study Completion Date: May 2013
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
  • Dose level 1: 100 mg/m2
  • Dose level 2: 140 mg/m2
  • Dose level 3: 170 mg/m2
  • Dose level 4: 200 mg/m2
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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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: July 9, 2013
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
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 July 29, 2014