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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

Primary Purpose

Lymphoma

Status
Completed
Phase
Phase 1
Locations
Switzerland
Study Type
Interventional
Intervention
ibritumomab tiuxetan
rituximab
melphalan
vinorelbine tartrate / G-CSF
autologous hematopoietic stem cell harvesting and transplantation
Sponsored by
Swiss Group for Clinical Cancer Research
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Lymphoma focused on measuring 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

Eligibility Criteria

65 Years - 120 Years (Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Kantonsspital Aarau
  • Saint Claraspital AG
  • Universitaetsspital-Basel
  • Istituto Oncologico della Svizzera Italiana - Ospedale Regionale Bellinzona e Valli
  • Inselspital Bern
  • Kantonsspital Liestal
  • Kantonsspital Bruderholz
  • Hopital Cantonal Universitaire de Geneve
  • Centre Hospitalier Universitaire Vaudois
  • Kantonsspital - St. Gallen

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Zevalin, Rituximab, Melphalan

Arm Description

Outcomes

Primary Outcome Measures

Dose-limiting toxicity of high-dose melphalan in combination with yttrium Y 90 ibritumomab tiuxetan

Secondary Outcome Measures

Toxicity
Event occurrence up to 100 days after transplantation
Complete remission 100 days after transplantation

Full Information

First Posted
October 25, 2006
Last Updated
May 13, 2019
Sponsor
Swiss Group for Clinical Cancer Research
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1. Study Identification

Unique Protocol Identification Number
NCT00392691
Brief Title
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
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 Type
Interventional

2. Study Status

Record Verification Date
May 2019
Overall Recruitment Status
Completed
Study Start Date
October 2006 (undefined)
Primary Completion Date
December 2012 (Actual)
Study Completion Date
May 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Swiss Group for Clinical Cancer Research

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Lymphoma
Keywords
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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
20 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Zevalin, Rituximab, Melphalan
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
ibritumomab tiuxetan
Other Intervention Name(s)
ZEVALIN
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
rituximab
Other Intervention Name(s)
MabThera
Intervention Description
250 mg/m2
Intervention Type
Drug
Intervention Name(s)
melphalan
Other Intervention Name(s)
Alkeran
Intervention Description
Dose level 1: 100 mg/m2 Dose level 2: 140 mg/m2 Dose level 3: 170 mg/m2 Dose level 4: 200 mg/m2
Intervention Type
Drug
Intervention Name(s)
vinorelbine tartrate / G-CSF
Other Intervention Name(s)
Navelbine
Intervention Description
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
Intervention Type
Procedure
Intervention Name(s)
autologous hematopoietic stem cell harvesting and transplantation
Intervention Description
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.
Primary Outcome Measure Information:
Title
Dose-limiting toxicity of high-dose melphalan in combination with yttrium Y 90 ibritumomab tiuxetan
Time Frame
within 8 weeks after application of melphalan
Secondary Outcome Measure Information:
Title
Toxicity
Time Frame
100 days (+/- 5 days) after reinfusion of stem cells
Title
Event occurrence up to 100 days after transplantation
Time Frame
up to 100 days after transplantation
Title
Complete remission 100 days after transplantation
Time Frame
100 days after transplantation

10. Eligibility

Sex
All
Minimum Age & Unit of Time
65 Years
Maximum Age & Unit of Time
120 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Michele Voegeli, MD
Organizational Affiliation
Kantonsspital Liestal
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Michele Ghielmini, Prof
Organizational Affiliation
IOSI, Ospedale San Giovanni
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Angelika Bischof Delaloye, Prof
Organizational Affiliation
Faculté de biologie et de médecine de l' Université de Lausanne
Official's Role
Study Chair
Facility Information:
Facility Name
Kantonsspital Aarau
City
Aarau
ZIP/Postal Code
CH-5001
Country
Switzerland
Facility Name
Saint Claraspital AG
City
Basel
ZIP/Postal Code
4016
Country
Switzerland
Facility Name
Universitaetsspital-Basel
City
Basel
ZIP/Postal Code
CH-4031
Country
Switzerland
Facility Name
Istituto Oncologico della Svizzera Italiana - Ospedale Regionale Bellinzona e Valli
City
Bellinzona
ZIP/Postal Code
6500
Country
Switzerland
Facility Name
Inselspital Bern
City
Bern
ZIP/Postal Code
3010
Country
Switzerland
Facility Name
Kantonsspital Liestal
City
Bern
ZIP/Postal Code
CH-3008
Country
Switzerland
Facility Name
Kantonsspital Bruderholz
City
Bruderholz
ZIP/Postal Code
4101
Country
Switzerland
Facility Name
Hopital Cantonal Universitaire de Geneve
City
Geneva
ZIP/Postal Code
CH-1211
Country
Switzerland
Facility Name
Centre Hospitalier Universitaire Vaudois
City
Lausanne
ZIP/Postal Code
CH-1011
Country
Switzerland
Facility Name
Kantonsspital - St. Gallen
City
St. Gallen
ZIP/Postal Code
CH-9007
Country
Switzerland

12. IPD Sharing Statement

Citations:
PubMed Identifier
27677906
Citation
Voegeli M, Rondeau S, Berardi Vilei S, Lerch E, Wannesson L, Pabst T, Rentschler J, Bargetzi M, Jost L, Ketterer N, Bischof Delaloye A, Ghielmini M. Y90 -Ibritumomab tiuxetan (Y90 -IT) and high-dose melphalan as conditioning regimen before autologous stem cell transplantation for elderly patients with lymphoma in relapse or resistant to chemotherapy: a feasibility trial (SAKK 37/05). Hematol Oncol. 2017 Dec;35(4):576-583. doi: 10.1002/hon.2348. Epub 2016 Sep 28.
Results Reference
result

Learn more about this trial

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

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