NCT00073918

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

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
111

participants targeted

Target at P50-P75 for phase_2

Timeline
Completed

Started Feb 1999

Longer than P75 for phase_2

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

February 1, 1999

Completed
4.9 years until next milestone

First Submitted

Initial submission to the registry

December 10, 2003

Completed
1 day until next milestone

First Posted

Study publicly available on registry

December 11, 2003

Completed
7.8 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

October 2, 2011

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

October 2, 2011

Completed
5.3 years until next milestone

Results Posted

Study results publicly available

January 27, 2017

Completed
Last Updated

August 18, 2017

Status Verified

July 1, 2017

Enrollment Period

12.7 years

First QC Date

December 10, 2003

Results QC Date

December 2, 2016

Last Update Submit

July 21, 2017

Conditions

Anaplastic Large Cell LymphomaCutaneous B-cell Non-Hodgkin LymphomaExtranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid TissueNodal Marginal Zone B-cell LymphomaRecurrent Adult Burkitt LymphomaRecurrent Adult Diffuse Large Cell LymphomaRecurrent Adult Diffuse Mixed Cell LymphomaRecurrent Adult Diffuse Small Cleaved Cell LymphomaRecurrent Adult Immunoblastic Large Cell LymphomaRecurrent Adult Lymphoblastic LymphomaRecurrent Grade 1 Follicular LymphomaRecurrent Grade 2 Follicular LymphomaRecurrent Grade 3 Follicular LymphomaRecurrent Mantle Cell LymphomaRecurrent Marginal Zone LymphomaSplenic Marginal Zone LymphomaWaldenström Macroglobulinemia

Outcome Measures

Primary Outcomes (1)

  • 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

Secondary Outcomes (3)

  • 5 Year Overall Survival

    Up to 15 years

  • Response Rate

    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

    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

Study Arms (1)

Treatment (radio labeled monoclonal antibody, chemotherapy)

EXPERIMENTAL

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: cyclophosphamideDrug: etoposideRadiation: iodine I 131 tositumomabProcedure: quality-of-life assessmentProcedure: peripheral blood stem cell transplantation

Interventions

cyclophosphamideDRUG

Given IV

Also known as: CPM, CTX, Cytoxan, Endoxan, Endoxana
Treatment (radio labeled monoclonal antibody, chemotherapy)
etoposideDRUG

Given IV

Also known as: EPEG, VP-16, VP-16-213
Treatment (radio labeled monoclonal antibody, chemotherapy)
iodine I 131 tositumomabRADIATION

Given IV

Also known as: 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
Treatment (radio labeled monoclonal antibody, chemotherapy)
quality-of-life assessmentPROCEDURE

Ancillary study

Also known as: quality of life assessment
Treatment (radio labeled monoclonal antibody, chemotherapy)
peripheral blood stem cell transplantationPROCEDURE

Undergo ASCT given via central catheter

Also known as: PBPC transplantation, PBSC transplantation, peripheral blood progenitor cell transplantation, transplantation, peripheral blood stem cell
Treatment (radio labeled monoclonal antibody, chemotherapy)

Eligibility Criteria

Age18 Years - 60 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64)

You may qualify if:

  • 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

You may not qualify if:

  • 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)

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

Seattle, Washington, 98109, United States

Location

MeSH Terms

Conditions

Lymphoma, Large-Cell, AnaplasticLymphoma, B-Cell, Marginal ZoneBurkitt LymphomaLymphoma, Large B-Cell, DiffuseLymphoma, Non-HodgkinLymphoma, Large-Cell, ImmunoblasticPrecursor Cell Lymphoblastic Leukemia-LymphomaLymphoma, FollicularLymphoma, Mantle-CellWaldenstrom Macroglobulinemia

Interventions

CyclophosphamideEtoposidetositumomab I-131Peripheral Blood Stem Cell Transplantation

Condition Hierarchy (Ancestors)

Lymphoma, T-CellLymphomaNeoplasms by Histologic TypeNeoplasmsLymphoproliferative DisordersLymphatic DiseasesHemic and Lymphatic DiseasesImmunoproliferative DisordersImmune System DiseasesLymphoma, B-CellEpstein-Barr Virus InfectionsHerpesviridae InfectionsDNA Virus InfectionsVirus DiseasesInfectionsTumor Virus InfectionsLeukemia, LymphoidLeukemiaHematologic DiseasesNeoplasms, Plasma CellHemostatic DisordersVascular DiseasesCardiovascular DiseasesParaproteinemiasBlood Protein DisordersHemorrhagic Disorders

Intervention Hierarchy (Ancestors)

Phosphoramide MustardsNitrogen Mustard CompoundsMustard CompoundsHydrocarbons, HalogenatedHydrocarbonsOrganic ChemicalsPhosphoramidesOrganophosphorus CompoundsPodophyllotoxinTetrahydronaphthalenesNaphthalenesPolycyclic Aromatic HydrocarbonsHydrocarbons, AromaticHydrocarbons, CyclicPolycyclic CompoundsGlucosidesGlycosidesCarbohydratesHematopoietic Stem Cell TransplantationStem Cell TransplantationCell TransplantationCell- and Tissue-Based TherapyBiological TherapyTherapeuticsTransplantationSurgical Procedures, Operative

Results Point of Contact

Title
Ajay K. Gopal, MD
Organization
Fred Hutchinson Cancer Research Center
agopal@u.washington.edu
206-288-2037

Study Officials

  • Ajay Gopal

    Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

    PRINCIPAL INVESTIGATOR

Publication Agreements

PI is Sponsor Employee
Yes

Study Design

Study Type
interventional
Phase
phase 2
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Principal Investigator

Study Record Dates

First Submitted

December 10, 2003

First Posted

December 11, 2003

Study Start

February 1, 1999

Primary Completion

October 2, 2011

Study Completion

October 2, 2011

Last Updated

August 18, 2017

Results First Posted

January 27, 2017

Record last verified: 2017-07

Locations

US(1)