- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00110071
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
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
Study Overview
Status
Conditions
- 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
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.
Study Type
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Locations
-
-
Washington
-
Seattle, Washington, United States, 98109
- Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
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.
|
Correlative studies
Given IV
Other Names:
Undergo transplantation (infusion of autologous or syngeneic PBSC via central line)
Other Names:
Given IV (dosimetric dose) or via central line (therapeutic dose)
Other Names:
Correlative studies
Correlative studies
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Maximum tolerated dose/dose limiting toxicity
Time Frame: Up to 30 days post-transplant
|
Assessed according to Bearman scale for Regimen-Related Toxicities.
|
Up to 30 days post-transplant
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Overall and progression-free survival rate
Time Frame: Up to 6 years
|
Up to 6 years
|
|
Response rate
Time Frame: Up to 12 months
|
Up to 12 months
|
|
Toxicity/tolerability of study regimen
Time Frame: Through day 100 post-transplant
|
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.
|
Through day 100 post-transplant
|
Feasibility of concurrent high-dose radioimmunotherapy and chemotherapy
Time Frame: Through day -7 prior to transplant
|
Ability to administer complete course of I 131-tositumomab and fludarabine phosphate as descried in protocol.
|
Through day -7 prior to transplant
|
Collaborators and Investigators
Sponsor
Collaborators
Publications and helpful links
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Pathologic Processes
- Cardiovascular Diseases
- Vascular Diseases
- Virus Diseases
- Infections
- Immune System Diseases
- Neoplasms by Histologic Type
- Neoplasms
- Lymphoproliferative Disorders
- Lymphatic Diseases
- Immunoproliferative Disorders
- Disease Attributes
- Hematologic Diseases
- Hemorrhagic Disorders
- Hemostatic Disorders
- Paraproteinemias
- Blood Protein Disorders
- DNA Virus Infections
- Tumor Virus Infections
- Neoplasms, Plasma Cell
- Leukemia, Lymphoid
- Leukemia
- Epstein-Barr Virus Infections
- Herpesviridae Infections
- Lymphoma
- Lymphoma, Follicular
- Lymphoma, B-Cell
- Lymphoma, Large B-Cell, Diffuse
- Recurrence
- Lymphoma, Non-Hodgkin
- Burkitt Lymphoma
- Lymphoma, Mantle-Cell
- Lymphoma, B-Cell, Marginal Zone
- Precursor Cell Lymphoblastic Leukemia-Lymphoma
- Lymphoma, Large-Cell, Immunoblastic
- Plasmablastic Lymphoma
- Waldenstrom Macroglobulinemia
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Anti-Infective Agents, Local
- Anti-Infective Agents
- Antimetabolites, Antineoplastic
- Antimetabolites
- Antineoplastic Agents
- Immunosuppressive Agents
- Immunologic Factors
- Trace Elements
- Micronutrients
- Antibodies
- Immunoglobulins
- Antibodies, Monoclonal
- Iodine
- Cadexomer iodine
- Antineoplastic Agents, Immunological
- Fludarabine
- Fludarabine phosphate
- Tositumomab I-131
Other Study ID Numbers
- 1943.00
- NCI-2009-01470 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
- P01CA044991 (U.S. NIH Grant/Contract)
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
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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