Iodine I 131 Tositumomab and Fludarabine Phosphate in Treating Older Patients Who Are Undergoing an Autologous or Syngeneic Stem Cell Transplant for Relapsed or Refractory Non-Hodgkin's Lymphoma

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Fred Hutchinson Cancer Research Center
ClinicalTrials.gov Identifier:
NCT00110071
First received: May 3, 2005
Last updated: August 4, 2014
Last verified: August 2014
  Purpose

This phase I trial studies the side effects and best dose of fludarabine (fludarabine phosphate) when given together with iodine I 131 tositumomab in treating older patients who are undergoing an autologous or syngeneic stem cell transplant for relapsed or refractory B-cell non-Hodgkin's lymphoma (NHL). Radiolabeled monoclonal antibodies, such as iodine I 131 tositumomab, can find cancer cells and carry cancer-killing substances to them without harming normal cells. Drugs used in chemotherapy, such as fludarabine, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. A peripheral stem cell transplant may be able to replace blood-forming cells that were destroyed by chemotherapy and radiation therapy. Giving iodine I 131 tositumomab together with fludarabine followed by autologous stem cell transplant may be an effective treatment for NHL


Condition Intervention Phase
Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue
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
Waldenström Macroglobulinemia
Drug: fludarabine phosphate
Procedure: peripheral blood stem cell transplantation
Radiation: iodine I 131 tositumomab
Other: laboratory biomarker analysis
Other: flow cytometry
Genetic: polymerase chain reaction
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Clinical Trial Evaluating I131-Tositumomab (Anti-CD20) With Escalating Doses of Fludarabine Followed by Autologous or Syngeneic Stem Cell Transplantation for Relapsed or Refractory B-cell Non-Hodgkin's Lymphoma in Patients 60 Years of Age and Older

Resource links provided by NLM:


Further study details as provided by Fred Hutchinson Cancer Research Center:

Primary Outcome Measures:
  • Maximum tolerated dose/dose limiting toxicity [ Time Frame: Up to 30 days post-transplant ] [ Designated as safety issue: Yes ]
    Assessed according to Bearman scale for Regimen-Related Toxicities.


Secondary Outcome Measures:
  • Overall and progression-free survival rate [ Time Frame: Up to 6 years ] [ Designated as safety issue: No ]
  • Response rate [ Time Frame: Up to 12 months ] [ Designated as safety issue: No ]
  • Toxicity/tolerability of study regimen [ Time Frame: Through day 100 post-transplant ] [ Designated as safety issue: Yes ]
    Type, frequency, and severity of adverse events grade 3 and above (assessed by National Cancer Institute (NCI) common terminology criteria for adverse events (CTCAE) v3.0.

  • Feasibility of concurrent high-dose radioimmunotherapy and chemotherapy [ Time Frame: Through day -7 prior to transplant ] [ Designated as safety issue: No ]
    Ability to administer complete course of I 131-tositumomab and fludarabine phosphate as descried in protocol.


Enrollment: 38
Study Start Date: January 2005
Primary Completion Date: June 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (chemoradioimmunotherapy)
Patients receive a dosimetric dose of iodine I 131 tositumomab IV over 40-60 minutes on day -24 followed by gamma camera imaging over the next 6 days. Patients then receive a therapeutic dose of iodine I 131 tositumomab via central line over 40-60 minutes on day -14. Patients also receive fludarabine phosphate IV QD on days -11 to -9 OR days -11 or -7. Patients undergo autologous or syngeneic peripheral blood stem cell transplantation on day 0.
Drug: fludarabine phosphate
Given IV
Other Names:
  • 2-F-ara-AMP
  • Beneflur
  • Fludara
Procedure: peripheral blood stem cell transplantation
Undergo transplantation (infusion of autologous or syngeneic PBSC via central line)
Other Names:
  • PBPC transplantation
  • PBSC transplantation
  • peripheral blood progenitor cell transplantation
  • transplantation, peripheral blood stem cell
Radiation: iodine I 131 tositumomab
Given IV (dosimetric dose) or via central line (therapeutic dose)
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
Other: laboratory biomarker analysis
Correlative studies
Other: flow cytometry
Correlative studies
Genetic: polymerase chain reaction
Correlative studies
Other Name: PCR

Detailed Description:

PRIMARY OBJECTIVES:

I. To estimate the maximally tolerated dose of fludarabine that can be combined with 131I-anti-CD20 (iodine I 131 tositumomab) delivering =< 27Gy to critical normal organs followed by autologous or syngeneic transplantation in patients >= 60 years of age with relapsed B-NHL.

SECONDARY OBJECTIVES:

I. To assess the overall and progression-free survival of the above regimen in such patients.

II. To evaluate the response rates of the above therapy.

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

IV. To evaluate the feasibility of delivering concurrent high-dose radioimmunotherapy (RIT) and chemotherapy.

OUTLINE: This is a dose-escalation study of fludarabine phosphate as used in combination with I 131 tositumomab and stem cell transplant.

Patients receive a dosimetric dose of iodine I 131 tositumomab intravenously (IV) over 40-60 minutes on day -24 followed by gamma camera imaging over the next 6 days. Patients then receive a therapeutic dose of iodine I 131 tositumomab via central line over 40-60 minutes on day -14. Patients also receive fludarabine phosphate IV once daily (QD) on days -11 to -9 OR days -11 or -7. Patients undergo autologous or syngeneic peripheral blood stem cell transplantation on day 0.

Patients with circulating lymphoma cells by peripheral smear receive tositumomab IV over 1 hour OR rituximab IV over 1 hour followed by tositumomab IV over 1 hour before the dosimetric iodine I 131 tositumomab infusion.

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

  Eligibility

Ages Eligible for Study:   60 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients must have a histologically confirmed diagnosis of lymphoma expressing the CD20 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
  • Creatinine (Cr) < 2.0
  • Bilirubin < 1.5 mg/dL, with the exception of patients thought to have Gilbert's syndrome, whom may have a total bilirubin above 1.5 mg/dL
  • All patients eligible for therapeutic study must have (>= 2x10^6 CD34/kg) autologous hematopoietic stem cells harvested and cryopreserved, or this number of cells harvested from a syngeneic donor
  • Patients must have an expected survival of > 60 days and must be free of major infection
  • DONOR: Syngeneic donors must be confirmed syngeneic by ABO typing, human leukocyte antigen (HLA) typing, and variable number tandem repeat (VNTR) analysis
  • DONOR: Syngeneic donors must meet eligibility under Standard Practice Guidelines/Standard Treatment

Exclusion Criteria:

  • Circulating anti-mouse antibody (HAMA) (to be determined before both dosimetry and therapy)
  • Systemic anti-lymphoma therapy given in the previous 30 days before the scheduled therapy dose
  • Inability to understand or give an informed consent
  • Prior radiation > 20 Gy to any critical normal organ (e.g., lung, liver, spinal cord, > 25% of red marrow)
  • Central nervous system lymphoma
  • Other serious medical conditions considered to represent contraindications to bone marrow transplant (BMT) (e.g., abnormally decreased cardiac ejection fraction, diffusing capacity (DLCO) < 50% predicted, patient on supplemental oxygen, acquired Immunodeficiency syndrome [AIDS], etc.)
  • Pregnancy
  • Prior bone marrow or stem cell transplant
  • South West Oncology Group (SWOG) performance status >= 2
  • Unable to perform self-care during radiation isolation
  • Patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma/well differentiated lymphocytic lymphoma
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00110071

Locations
United States, Washington
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
Seattle, Washington, United States, 98109
Sponsors and Collaborators
Fred Hutchinson Cancer Research Center
Investigators
Principal Investigator: Ajay Gopal Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
  More Information

No publications provided

Responsible Party: Fred Hutchinson Cancer Research Center
ClinicalTrials.gov Identifier: NCT00110071     History of Changes
Other Study ID Numbers: 1943.00, NCI-2009-01470, P01CA044991
Study First Received: May 3, 2005
Last Updated: August 4, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Lymphoma, Non-Hodgkin
Lymphoma, B-Cell
Lymphoma, Follicular
Burkitt Lymphoma
Lymphoma, Large-Cell, Immunoblastic
Waldenstrom Macroglobulinemia
Lymphoma, B-Cell, Marginal Zone
Lymphoma, Mantle-Cell
Lymphoma, Large B-Cell, Diffuse
Lymphoma
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Epstein-Barr Virus Infections
Herpesviridae Infections
DNA Virus Infections
Virus Diseases
Tumor Virus Infections
Neoplasms, Experimental
Neoplasms, Plasma Cell
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders

ClinicalTrials.gov processed this record on September 16, 2014