Brief Title
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
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
Brief Summary
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
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 Phase
Phase 1
Study Type
Interventional
Primary Outcome
Maximum tolerated dose/dose limiting toxicity
Secondary Outcome
Overall and progression-free survival rate
Condition
Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue
Intervention
fludarabine phosphate
Study Arms / Comparison Groups
Treatment (chemoradioimmunotherapy)
Description: 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.
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Drug
Estimated Enrollment
38
Start Date
January 2005
Primary Completion Date
June 2011
Eligibility 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
Gender
All
Ages
60 Years - N/A
Accepts Healthy Volunteers
No
Contacts
Ajay Gopal, ,
Location Countries
United States
Location Countries
United States
Administrative Informations
NCT ID
NCT00110071
Organization ID
1943.00
Secondary IDs
NCI-2009-01470
Responsible Party
Sponsor
Study Sponsor
Fred Hutchinson Cancer Center
Collaborators
National Cancer Institute (NCI)
Study Sponsor
Ajay Gopal, Principal Investigator, Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
Verification Date
August 2014