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

Recurrent Mantle Cell Lymphoma Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00073918
• Other study ID #: 1368.00
• Secondary ID: NCI-2009-01469P0
• Status: Completed
• Phase: Phase 2
• First received: December 10, 2003
• Last updated: August 4, 2014
• Start date: February 1999

Study information

• Verified date: August 2014
• Source: Fred Hutchinson Cancer Research Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 112
• Est. primary completion date: July 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 60 Years

Eligibility

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 Design

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Anaplastic Large Cell Lymphoma
• Burkitt Lymphoma
• Cutaneous B-cell Non-Hodgkin Lymphoma
• Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue
• Lymphoma
• Lymphoma, B-Cell
• Lymphoma, B-Cell, Marginal Zone
• Lymphoma, Follicular
• Lymphoma, Large B-Cell, Diffuse
• Lymphoma, Large-Cell, Anaplastic
• Lymphoma, Large-Cell, Immunoblastic
• Lymphoma, Mantle-Cell
• Lymphoma, Non-Hodgkin
• Nodal Marginal Zone B-cell Lymphoma
• 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
• Splenic Marginal Zone Lymphoma
• Waldenstrom Macroglobulinemia
• Waldenström Macroglobulinemia

Intervention

Drug:
• cyclophosphamide
Given IV
• etoposide
Given IV

Radiation:
• iodine I 131 tositumomab
Given IV

Procedure:
• quality-of-life assessment
Ancillary study
• peripheral blood stem cell transplantation
Undergo ASCT given via central catheter

Locations

Country	Name	City	State
United States	Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium	Seattle	Washington

Sponsors (2)

Lead Sponsor	Collaborator
Fred Hutchinson Cancer Research Center	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression-free survival	Kaplan-Meier estimate of progression-free survival at 3 years will be used as the primary determinant of potential efficacy.	At year 3	No
Secondary	Overall survival	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	No
Secondary	Response rate	Response rates will be estimated as simple proportions. Associated confidence intervals will be provided as part of the analysis.	From date of transplant through date of relapse/progression or death, assessed up to 15 years	No
Secondary	Toxicity as assessed by Common Terminology Criteria (CTC) v 2.0	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%,, where these limits are estimated after every 10th patient is enrolled and followed sufficiently long to evaluate toxicity.	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	Yes