Follicular LymphomaPhase 2NCT01389076
Trial of Low-Dose Methotrexate and I 131 Tositumomab for Previously Untreated, Advanced-Stage, Follicular Lymphoma
A Phase 2 study testing Bexxar and Low Dose Methotrexate in people with Follicular Lymphoma, run by University of Michigan Rogel Cancer Center at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Follicular Lymphoma
- What is being tested?
- Bexxar and Low Dose Methotrexate
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 22 participants
- Where
- 1 siteUnited States
- Study dates
- Jul 2011to Jun 2016
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: 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.
Read the 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.
- Conditions
- Follicular Lymphoma
- Being tested
- Bexxar, Low Dose Methotrexate
- Keywords
- Previously Untreated, Advanced-Stage, Follicular Lymphoma
- Medical subject headings
- Lymphoma, Follicular
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BexxarDrug
Also called Iodine I 131 tositumomab
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.
Low Dose MethotrexateDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| Treatment arm | Experimental | Low dose methotrexate and Bexxar Receives: Drug: Bexxar; Drug: Low Dose Methotrexate |
What is being measured
The primary outcome is the main question the study is designed to answer.
Rate of Early Onset HAMA (Human Anti-mouse Antibody) Conversion Following Treatment
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.
Measured: 7 weeks
Secondary outcomes (4)
Percentage of Participants That Respond to Treatment
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.
Measured: 2 years
The Percentage of Participants Alive at 2 Years
Overall survival was examined at 2 years
Measured: 2 years
Median Progression Free Survival (PFS) Time
The median time patients survived without progression.
Measured: 2 Years
Number of Participants That Experienced SAEs During Treatment.
Measured: Up to week 13
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Jul 2011 (estimated)
- Study startJul 2011
- Primary completionFeb 2014
- Study completionJun 2016
Why it stopped: Bexxar isn't being produced by the manufacturer as of Feb. 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Follicular LymphomaStudies of the same condition, open and under way.
- More trials run by University of Michigan Rogel Cancer CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 22 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Michigan Rogel Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- GlaxoSmithKline
- Responsible party
- Sponsor
- Investigators
- Mark Kaminski, M.D., Principal investigator, University of Michigan
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01389076
- Sponsor's protocol ID
- UMCC 2010.098
- Other IDs
- HUM00043235
- Status last verified
- Dec 2016
- First submitted
- 5 Jul 2011
- Last updated
- 30 Jan 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 30 Jan 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Trial of Low-Dose Methotrexate and Iodine I 131 Tositumomab for Previously Untreated, Advanced-Stage, Follicular Lymphoma
- ClinicalTrials.gov ID
- NCT01389076
- Acronym / sponsor ID
- UMCC 2010.098
- Conditions
- Follicular Lymphoma
- Keywords
- Previously Untreated, Advanced-Stage, Follicular Lymphoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Bexxar isn't being produced by the manufacturer as of Feb. 2014
- Enrolment
- 22 participants (actual)
- Lead sponsor
- University of Michigan Rogel Cancer CenterUniversity, hospital or other
- Collaborators
- GlaxoSmithKline
- Study start
- Jul 2011
- Primary completion
- Feb 2014 (actual)
- Study completion
- Jun 2016 (actual)
- First posted
- 7 Jul 2011 (estimated)
- Results
- Posted 12 Jul 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment arm | Experimental | Drug: Bexxar, Drug: Low Dose MethotrexateLow dose methotrexate and Bexxar |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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.
Key exclusion criteria (13 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BexxarAlso: Iodine I 131 tositumomabIodine 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. | Drug | Treatment arm |
| Low Dose MethotrexateMethotrexate 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. | Drug | Treatment arm |
Primary outcome
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.
4 secondary outcomes
Percentage of Participants That Respond to Treatment
Time frame: 2 years
The Percentage of Participants Alive at 2 Years
Time frame: 2 years
Median Progression Free Survival (PFS) Time
Time frame: 2 Years
Number of Participants That Experienced SAEs During Treatment.
Time frame: Up to week 13
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Jan 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Mark Kaminski, M.D. principal investigator
University of Michigan
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Bexxar and Low Dose Methotrexate in people with Follicular Lymphoma, run by University of Michigan Rogel Cancer Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 30 Jan 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 12 Jul 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Rate of Early Onset HAMA (Human Anti-mouse Antibody) Conversion Following Treatment (time frame: 7 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Jan 2017.