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

May 13, 2019 updated by: Swiss Group for Clinical Cancer Research

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

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.

Study Overview

Status

Completed

Conditions

Intervention / 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.

Study Type

Interventional

Enrollment (Actual)

20

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Switzerland
      • Aarau, Switzerland, CH-5001
        • Kantonsspital Aarau
      • Basel, Switzerland, CH-4031
        • Universitaetsspital-Basel
      • Basel, Switzerland, 4016
        • Saint Claraspital AG
      • Bellinzona, Switzerland, 6500
        • Istituto Oncologico della Svizzera Italiana - Ospedale Regionale Bellinzona e Valli
      • Bern, Switzerland, 3010
        • Inselspital Bern
      • Bern, Switzerland, CH-3008
        • Kantonsspital Liestal
      • Bruderholz, Switzerland, 4101
        • Kantonsspital Bruderholz
      • Geneva, Switzerland, CH-1211
        • Hôpital Cantonal Universitaire de Genève
      • Lausanne, Switzerland, CH-1011
        • Centre Hospitalier Universitaire Vaudois
      • St. Gallen, Switzerland, CH-9007
        • Kantonsspital - St. Gallen

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

65 years to 120 years (Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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 Names:
  • ZEVALIN
Drug: rituximab
250 mg/m2
Other Names:
  • 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 Names:
  • 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 Names:
  • 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Dose-limiting toxicity of high-dose melphalan in combination with yttrium Y 90 ibritumomab tiuxetan
Time Frame: within 8 weeks after application of melphalan
within 8 weeks after application of melphalan

Secondary Outcome Measures

Outcome Measure
Time Frame
Toxicity
Time Frame: 100 days (+/- 5 days) after reinfusion of stem cells
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
up to 100 days after transplantation
Complete remission 100 days after transplantation
Time Frame: 100 days after transplantation
100 days after transplantation

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

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

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

October 1, 2006

Primary Completion (Actual)

December 1, 2012

Study Completion (Actual)

May 1, 2013

Study Registration Dates

First Submitted

October 25, 2006

First Submitted That Met QC Criteria

October 25, 2006

First Posted (Estimate)

October 26, 2006

Study Record Updates

Last Update Posted (Actual)

May 15, 2019

Last Update Submitted That Met QC Criteria

May 13, 2019

Last Verified

May 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • SAKK 37/05
  • SWS-SAKK-37/05
  • EU-20648
  • SPRI-SWS-SAKK-37/05
  • CDR0000511915

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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