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

Brief Title

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

Official Title

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

Brief Summary

      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
    

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 Phase

Phase 2

Study Type

Interventional

Primary Outcome

Progression-free Survival

Secondary Outcome

 5 Year Overall Survival

Condition

Anaplastic Large Cell Lymphoma

Intervention

cyclophosphamide

Study Arms / Comparison Groups

 Treatment (radio labeled monoclonal antibody, chemotherapy)

Description:  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.

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Status

Drug

Estimated Enrollment

111

Start Date

February 1999

Completion Date

October 2, 2011

Primary Completion Date

October 2, 2011

Eligibility Criteria

        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)
      

Gender

All

Ages

18 Years - 60 Years

Accepts Healthy Volunteers

No

Contacts

Ajay Gopal, , 

Location Countries

United States

Location Countries

United States

NCT ID

NCT00073918

Organization ID

1368.00

Secondary IDs

NCI-2009-01469

Responsible Party

Principal Investigator

Study Sponsor

Fred Hutchinson Cancer Research Center

Collaborators

 National Cancer Institute (NCI)

Study Sponsor

Ajay Gopal, Principal Investigator, Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

Verification Date

July 2017