- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01389076
Trial of Low-Dose Methotrexate and I 131 Tositumomab for Previously Untreated, Advanced-Stage, Follicular Lymphoma
December 1, 2016 updated by: University of Michigan Rogel Cancer Center
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.
Study Overview
Status
Terminated
Conditions
Intervention / Treatment
Detailed Description
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.
Study Type
Interventional
Enrollment (Actual)
22
Phase
- Phase 2
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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Michigan
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Ann Arbor, Michigan, United States, 48109
- University of Michigan
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
Inclusion Criteria:
- 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).
- Patients must have Ann Arbor Stage III or IV extent of disease after complete staging.
- Patients must have a willingness and ability to follow prescribed radiation precautions
- 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.
- 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.
- 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.
- 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.
- Patients must have bi-dimensionally measurable disease.
Exclusion Criteria:
- Patients with follicular Grade 3a or 3b by WHO Classification.
- Patients with evidence of active infection requiring IV antibiotics at the time of study entry.
- Patients with New York Heart Association Class III or IV heart disease or other serious illness that would preclude evaluation.
- Patients with active obstructive hydronephrosis.
- 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.
- Patients with known HIV infection.
- Patients with known brain or leptomeningeal metastases.
- 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.
- Patients with previous allergic reactions to iodine. This does not include reacting to IV iodine-containing contrast materials.
- Patients with previous allergic reactions to methotrexate.
- Patients who were previously given any monoclonal antibody, regardless of species, for any condition.
- Detectable serum levels of HAMA.
- Patients who are concurrently receiving either approved or non-approved (through another protocol) anti-cancer drugs or biologics.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
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 arm
Low dose methotrexate and Bexxar
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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 Names:
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.
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Rate of Early Onset HAMA (Human Anti-mouse Antibody) Conversion Following Treatment
Time Frame: 7 weeks
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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.
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7 weeks
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Percentage of Participants That Respond to Treatment
Time Frame: 2 years
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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. |
2 years
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The Percentage of Participants Alive at 2 Years
Time Frame: 2 years
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Overall survival was examined at 2 years
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2 years
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Median Progression Free Survival (PFS) Time
Time Frame: 2 Years
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The median time patients survived without progression.
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2 Years
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Number of Participants That Experienced SAEs During Treatment.
Time Frame: Up to week 13
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Up to week 13
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Collaborators
Investigators
- Principal Investigator: Mark Kaminski, M.D., University of Michigan
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
July 1, 2011
Primary Completion (Actual)
February 1, 2014
Study Completion (Actual)
June 1, 2016
Study Registration Dates
First Submitted
July 5, 2011
First Submitted That Met QC Criteria
July 6, 2011
First Posted (Estimate)
July 7, 2011
Study Record Updates
Last Update Posted (Estimate)
January 30, 2017
Last Update Submitted That Met QC Criteria
December 1, 2016
Last Verified
December 1, 2016
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Immune System Diseases
- Neoplasms by Histologic Type
- Neoplasms
- Lymphoproliferative Disorders
- Lymphatic Diseases
- Immunoproliferative Disorders
- Lymphoma, Non-Hodgkin
- Lymphoma
- Lymphoma, Follicular
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Nucleic Acid Synthesis Inhibitors
- Enzyme Inhibitors
- Antirheumatic Agents
- Antimetabolites, Antineoplastic
- Antimetabolites
- Antineoplastic Agents
- Immunosuppressive Agents
- Immunologic Factors
- Dermatologic Agents
- Reproductive Control Agents
- Abortifacient Agents, Nonsteroidal
- Abortifacient Agents
- Folic Acid Antagonists
- Tositumomab I-131
- Methotrexate
Other Study ID Numbers
- UMCC 2010.098
- HUM00043235 (Other Identifier: University of Michigan IRBMED)
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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