Iodine I 131 Tositumomab, Etoposide and Cyclophosphamide Followed by Autologous Stem Cell Transplant in Treating Patients With Relapsed or Refractory Non-Hodgkin's Lymphoma

July 21, 2017 updated by: Ajay Gopal, Fred Hutchinson Cancer Center

A Phase II Trial Evaluating The Efficacy of Radioiodinated Tositumomab (Anti-CD20) Antibody, Etoposide and Cyclophosphamide Followed by Autologous Transplantation, for Relapsed or Refractory Non-Hodgkin's Lymphoma

This phase II trial is studying how well giving iodine I 131 tositumomab together with etoposide and cyclophosphamide followed by autologous stem cell transplant works in treating patients with relapsed or refractory non-Hodgkin's lymphoma. Radiolabeled monoclonal antibodies, such as iodine I 131 tositumomab, can find cancer cells and deliver radioactive cancer-killing substances to them without harming normal cells. Drugs used in chemotherapy, such as etoposide and cyclophosphamide, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Combining a radiolabeled monoclonal antibody with combination chemotherapy before autologous stem cell transplant may kill more cancer cells

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

PRIMARY OBJECTIVES:

I. To assess the progression-free survival of patients receiving 131 I labeled tositumomab antibody, etoposide (VP-16) and cyclophosphamide (CY) followed by autologous transplantation.

II. To examine the potential efficacy of 131 I labeled tositumomab antibody, etoposide (VP-16) and cyclophosphamide (CY) followed by autologous transplantation.

SECONDARY OBJECTIVES:

I. To assess the overall survival of patients receiving 131 I labeled tositumomab antibody, etoposide (VP-16) and cyclophosphamide (CY) followed by autologous transplantation.

II. To evaluate the toxicity and tolerability of the above therapy.

OUTLINE:

RADIOIMMUNOTHERAPY: Patients receive a test dose of iodine I 131 tositumomab intravenously (IV) on day -24 to determine biodistribution. Patients then receive therapeutic iodine I 131 tositumomab IV over approximately 40-60 minutes on day -14 and are entered into radiation isolation until day -4.

CHEMOTHERAPY: Patients receive etoposide IV on day -4 and cyclophosphamide IV on day -2.

AUTOLOGOUS STEM CELL TRANSPLANTATION: Patients undergo autologous peripheral blood stem cell transplant on day 0.

After completion of study treatment, patients are followed at 1, 3, 6, and 12 months and then annually thereafter.

Study Type

Interventional

Enrollment (Actual)

111

Phase

  • Phase 2

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

  • United States
    • Washington
      • Seattle, Washington, United States, 98109
        • Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

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

18 years to 60 years (ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Patients must have a histologically confirmed diagnosis of lymphoma expressing the cluster of differentiation (CD)20 antigen and generally must have failed at least one prior standard systemic therapy; the exception will be mantle cell lymphoma (MCL) patients, who may be enrolled while in first complete remission (CR) in accordance with current transplant standard of care for these patients
  • Note: Patients with clinically non-transformed follicular lymphomas do not require repeat biopsies for immunophenotyping since these tumors are uniformly reactive with the tositumomab antibody
  • Patients must have tumor burdens < 500cc by computed tomography (CT) or magnetic resonance (MRI) volumetric measurements and must not have splenomegaly at the time of enrollment; splenomegaly will be defined as a spleen volume > 2 standard deviations of the mean spleen volume to body weight ratio (mean = 3.84 cc/kg, SD = 1.53 cc/kg); thus, patients with > 6.9cc/kg will be defined as having splenomegaly; patients with splenomegaly that is thought to be due to G CSF/GM-CSF effect and not due to lymphomatous involvement of the spleen can been deemed eligible with the approval of an investigator
  • Patients must have normal renal function (creatinine [Cr] < 2.0)
  • Patients must have normal hepatic function (bilirubin < 1.5mg/dL), with the exception of patients thought to have Gilbert's syndrome, who may have a total bilirubin above 1.5mg/dL
  • All patients eligible for therapeutic study must have autologous hematopoietic stem cells (2 x 10^6 CD34+ cells/kg) harvested and cryopreserved
  • Patients must have an expected survival of > 60 days and must be free of major infection

Exclusion Criteria:

  • Circulating anti-mouse antibody (HAMA)
  • Systemic anti-lymphoma therapy given within 30 days prior to anticipated treatment date
  • Inability to understand or give an informed consent
  • Prior radiation > 20 Gy to any critical normal organ (e.g., lung, liver, spinal cord, or over 25% of red marrow)
  • Central nervous system lymphoma
  • Other serious medical conditions considered to represent contraindications to autologous stem cell transplant (ASCT) (e.g., active coronary artery disease, pulmonary dysfunction [forced expiratory volume in 1 second (FEV1) < 70% expected, Vital Capacity < 70% expected, diffusing capacity of the lung for carbon monoxide (DLCO) < 50%, patient on supplemental oxygen], AIDS, etc.)
  • Pregnancy
  • Prior bone marrow or stem cell transplant
  • Presence of circulating lymphoma cells by morphology or flow cytometry (>= 0.1%) at or near the time of peripheral blood stem cell (PBSC) collection if unpurged PBSC are to be used
  • Southwest Oncology Group (SWOG) performance status >= 2.0
  • Unable to perform self-care during radiation isolation
  • Patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma/well differentiated lymphocytic lymphoma (ineligible because these tumors express very low surface densities of CD20)

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: NA
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: Treatment (radio labeled monoclonal antibody, chemotherapy)

RADIOIMMUNOTHERAPY: Patients receive a test dose of iodine I 131 tositumomab IV on day -24 to determine biodistribution. Patients then receive therapeutic iodine I 131 tositumomab IV over approximately 40-60 minutes on day -14 and are entered into radiation isolation until day -4.

CHEMOTHERAPY: Patients receive etoposide IV on day -4 and cyclophosphamide IV on day -2.

AUTOLOGOUS STEM CELL TRANSPLANTATION: Patients undergo autologous peripheral blood stem cell transplantation on day 0.
Drug: cyclophosphamide
Given IV
Other Names:
  • Cytoxan
  • Endoxan
  • CPM
  • CTX
  • Endoxana
Drug: etoposide
Given IV
Other Names:
  • EPEG
  • VP-16
  • VP-16-213
Procedure: quality-of-life assessment
Ancillary study
Other Names:
  • quality of life assessment
Radiation: iodine I 131 tositumomab
Given IV
Other Names:
  • 131-I-anti-B1 antibody
  • 131-I-anti-B1 monoclonal antibody
  • I131-MOAB-B1
  • iodine I 131 MOAB anti-B1
  • iodine I 131 monoclonal antibody anti-B1
Procedure: peripheral blood stem cell transplantation
Undergo ASCT given via central catheter
Other Names:
  • PBPC transplantation
  • PBSC transplantation
  • peripheral blood progenitor cell transplantation
  • transplantation, peripheral blood stem cell

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression-free Survival
Time Frame: At year 3
Kaplan-Meier estimate of progression-free survival at 3 years will be used as the primary determinant of potential efficacy.
At year 3

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
5 Year Overall Survival
Time Frame: Up to 15 years
Survival will be estimated using the method of Kaplan and Meier. Associated confidence intervals will be provided as part of the analysis.
Up to 15 years
Response Rate
Time Frame: From date of transplant through date of relapse/progression or death, assessed up to 15 years
Response rates will be estimated as the percentage of patients
From date of transplant through date of relapse/progression or death, assessed up to 15 years
Toxicity as Assessed by Common Terminology Criteria (CTC) v 2.0
Time Frame: From date of first exposure to study drug, through date of relapse/progression or other significant medical event confounding further assessment, assessed up to 15 years
Grade 3-4 Bearman non-hematologic toxicity will be carefully monitored throughout this study. The protocol will be terminated due to safety concerns if there exists sufficient evidence suggesting that the true rate of grade 3-4 nonhematologic toxicity exceeds 25%. All patients, regardless of histology, will be evaluated together for purposes of toxicity. Sufficient evidence will be taken to be a lower limit to the appropriate 90% one-sided confidence interval in excess of 25%
From date of first exposure to study drug, through date of relapse/progression or other significant medical event confounding further assessment, assessed up to 15 years

Collaborators and Investigators

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

Sponsor

Fred Hutchinson Cancer Center

Collaborators

National Cancer Institute (NCI)

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

February 1, 1999

Primary Completion (ACTUAL)

October 2, 2011

Study Completion (ACTUAL)

October 2, 2011

Study Registration Dates

First Submitted

December 10, 2003

First Submitted That Met QC Criteria

December 10, 2003

First Posted (ESTIMATE)

December 11, 2003

Study Record Updates

Last Update Posted (ACTUAL)

August 18, 2017

Last Update Submitted That Met QC Criteria

July 21, 2017

Last Verified

July 1, 2017

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 1368.00
  • P01CA044991 (U.S. NIH Grant/Contract)
  • NCI-2009-01469 (REGISTRY: CTRP (Clinical Trial Reporting Program))

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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