Trial of Low-Dose Methotrexate and I 131 Tositumomab for Previously Untreated, Advanced-Stage, Follicular Lymphoma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01389076
Recruitment Status : Terminated (Bexxar isn't being produced by the manufacturer as of Feb. 2014)
First Posted : July 7, 2011
Results First Posted : July 12, 2016
Last Update Posted : January 30, 2017
Information provided by (Responsible Party):
University of Michigan Cancer Center

July 5, 2011
July 7, 2011
June 2, 2016
July 12, 2016
January 30, 2017
July 2011
February 2014   (Final data collection date for primary outcome measure)
Rate of Early Onset HAMA (Human Anti-mouse Antibody) Conversion Following Treatment [ Time Frame: 7 weeks ]
The percentage of patients that experience early onset HAMA conversion following treatment. Early-onset HAMA is defined as antimouse antibody levels (in blood serum) of at least 5 times the level of detection, occurring at or prior to the 7th week of I-131 tositumomab therapy.
To determine the rate of early onset HAMA conversion in previously untreated patients with advanced stage, low-grade follicular lymphoma undergoing treatment with I-131 tositumomab accompanied by methotrexate prophylaxis. [ Time Frame: 6 months ]
Complete list of historical versions of study NCT01389076 on Archive Site
  • Percentage of Participants That Respond to Treatment [ Time Frame: 2 years ]

    The overall response rate (PR [partial response] + CR [complete response]) was determined.

    Partial response is defined as the regression of measurable disease with no new sites of disease.

    Complete response is defined as the disappearance of all evidence of disease.

  • The Percentage of Participants Alive at 2 Years [ Time Frame: 2 years ]
    Overall survival was examined at 2 years
  • Median Progression Free Survival (PFS) Time [ Time Frame: 2 Years ]
    The median time patients survived without progression.
  • Number of Participants That Experienced SAEs During Treatment. [ Time Frame: Up to week 13 ]
  • To determine the overall, complete, and partial response rates to this therapy. [ Time Frame: 2 years ]
  • To estimate the progression-free and overall survival in this patient population. [ Time Frame: 2 years ]
  • To assess the safety of combination treatment with methotrexate and I-131 tositumomab. [ Time Frame: 6 months ]
  • To characterize the effect of prophylactic dose methotrexate on blood lymphocyte subsets by flow cytometry. [ Time Frame: 1 year ]
Not Provided
Not Provided
Trial of Low-Dose Methotrexate and I 131 Tositumomab for Previously Untreated, Advanced-Stage, Follicular Lymphoma
Phase II Trial of Low-Dose Methotrexate and Iodine I 131 Tositumomab for Previously Untreated, Advanced-Stage, Follicular Lymphoma
Patients with a type of non-Hodgkin lymphoma, called follicular lymphoma and have not yet had previous systemic treatment, such as chemotherapy or immunotherapy will be invited to participate. This research study is being conducted in order to evaluate the combination of lowdose methotrexate and Iodine I 131 tositumomab (Bexxar) with regards to whether the combination will reduce the occurrence of the HAMA (Human Anti-Mouse Antibody) response. HAMA is an immune reaction against the tositumomab protein. Symptoms arising from HAMA can range from a mild form, like a rash, to a more extreme and possibly life-threatening level. HAMA can also decrease the effectiveness of the treatment, or create a future reaction if a patient is given another treatment containing mouse antibodies. In addition to evaluating the occurrence of HAMA, this research study will also look at the short and long-term effectiveness of this combination in the treatment of lymphoma, as well as its safety.
This is a single-arm, single institution, Phase II study to test the use of low-dose methotrexate in combination with I-131 tositumomab for its ability to lower the rate of (human anti-mouse antibody) HAMA formation in patients with previously untreated low-grade follicular lymphoma. Low-dose methotrexate will be given beginning 3 weeks prior to the first infusion of I-131 tositumomab (4 weekly doses) and continued for 6 weeks (10 total doses), the period of time during which the development of HAMA is most detrimental. A total of 61 patients will be enrolled. The primary endpoint of the study is the determination of the rate of HAMA conversion within the first seven weeks following treatment. The secondary endpoints include response rates, progression-free and overall survival, and safety.
Phase 2
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Follicular Lymphoma
  • Drug: Bexxar
    Iodine I 131 tositumomab (Bexxar) is a radioimmunotherapy (RIT) drug. RIT is a treatment strategy designed to target radiation specifically to cancer cells by attaching a radioactive atom to a monoclonal antibody, an immune system protein that binds to a particular protein. The Iodine I 131 tositumomab (Bexxar) therapeutic regimen is delivered in two sets of intravenous infusions given about 7 days apart. Nonradioactive Tositumomab is given before both the "dosimetric" infusion and the "therapeutic" infusion to improve distribution of these doses throughout the body.
    Other Name: Iodine I 131 tositumomab
  • Drug: Low Dose Methotrexate
    Methotrexate is an antifolate drug. It interferes with cells' ability to copy their DNA. This mainly affects cells that are dividing frequently, such as immune system cells and cancer cells. Methotrexate will be used in this study to try to prevent the occurrence of HAMA by limiting your body's ability to produce anti mouse antibodies.
Experimental: Treatment arm
Low dose methotrexate and Bexxar
  • Drug: Bexxar
  • Drug: Low Dose Methotrexate
Not Provided

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
June 2016
February 2014   (Final data collection date for primary outcome measure)

Inclusion Criteria:

  1. Patients must have a histologically-confirmed diagnosis of follicular non-Hodgkin's B-cell lymphoma, grade 1-2 (grade 1 or grade 2 by WHO classification prior to 2009).
  2. Patients must have Ann Arbor Stage III or IV extent of disease after complete staging.
  3. Patients must have a willingness and ability to follow prescribed radiation precautions
  4. Patients must not have had any previous treatment for low-grade lymphoma including chemotherapy or radiation. They may be newly diagnosed or observed without treatment after diagnosis. Symptomatic and asymptomatic patients will be eligible.
  5. Patients must have a performance status of 0-2 on the Eastern Cancer Oncology Group (ECOG) scale and an anticipated survival of at least 3 months.
  6. Patients must have an absolute neutrophil count >1500 cells/mm3 and a platelet count >100,000 cells/mm3 within 14 days of study entry. These blood counts must be sustained without support of hematopoietic cytokines or transfusion of blood products.
  7. Patients must have adequate renal function (defined as serum creatinine <2.0) and hepatic function (defined as total bilirubin <1.5 x ULN and Aspartate Aminotransferase (AST) <3 x ULN) within 14 days of study entry.
  8. Patients must have bi-dimensionally measurable disease.

Exclusion Criteria:

  1. Patients with follicular Grade 3a or 3b by WHO Classification.
  2. Patients with evidence of active infection requiring IV antibiotics at the time of study entry.
  3. Patients with New York Heart Association Class III or IV heart disease or other serious illness that would preclude evaluation.
  4. Patients with active obstructive hydronephrosis.
  5. Patients with prior malignancy other than lymphoma, except for adequately treated skin cancer, in situ cervical cancer, or other cancer for which the patient has been disease-free for 5 years.
  6. Patients with known HIV infection.
  7. Patients with known brain or leptomeningeal metastases.
  8. Patients who are pregnant or nursing. Patients of childbearing potential must undergo a pregnancy test within 7 days of study entry and methotrexate is not to be administered until a negative result is obtained. Males and females must agree to use effective contraception for 6 months following the radioimmunotherapy.
  9. Patients with previous allergic reactions to iodine. This does not include reacting to IV iodine-containing contrast materials.
  10. Patients with previous allergic reactions to methotrexate.
  11. Patients who were previously given any monoclonal antibody, regardless of species, for any condition.
  12. Detectable serum levels of HAMA.
  13. Patients who are concurrently receiving either approved or non-approved (through another protocol) anti-cancer drugs or biologics.
Sexes Eligible for Study: All
18 Years and older   (Adult, Older Adult)
Contact information is only displayed when the study is recruiting subjects
United States
UMCC 2010.098
HUM00043235 ( Other Identifier: University of Michigan IRBMED )
Not Provided
Not Provided
University of Michigan Cancer Center
University of Michigan Cancer Center
Principal Investigator: Mark Kaminski, M.D. University of Michigan
University of Michigan Cancer Center
December 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP