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

Primary Purpose

Follicular Lymphoma

Status

Terminated

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

Bexxar

Low Dose Methotrexate

About this trial

This is an interventional treatment trial for Follicular Lymphoma focused on measuring Previously Untreated, Advanced-Stage, Follicular Lymphoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

University of Michigan

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment arm

Arm Description

Low dose methotrexate and Bexxar

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.

The Percentage of Participants Alive at 2 Years

Overall survival was examined at 2 years

Median Progression Free Survival (PFS) Time

The median time patients survived without progression.

Number of Participants That Experienced SAEs During Treatment.

Full Information

NCT ID

NCT01389076

First Posted

July 5, 2011

Last Updated

December 1, 2016

Sponsor

University of Michigan Rogel Cancer Center

Collaborators

GlaxoSmithKline

1. Study Identification

Unique Protocol Identification Number

NCT01389076

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

December 2016

Overall Recruitment Status

Terminated

Why Stopped

Bexxar isn't being produced by the manufacturer as of Feb. 2014

Study Start Date

July 2011 (undefined)

Primary Completion Date

February 2014 (Actual)

Study Completion Date

June 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

University of Michigan Rogel Cancer Center

Collaborators

GlaxoSmithKline

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief 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. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Follicular Lymphoma

Keywords

Previously Untreated, Advanced-Stage, Follicular Lymphoma

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

22 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Treatment arm

Arm Type

Experimental

Arm Description

Low dose methotrexate and Bexxar

Intervention Type

Drug

Intervention Name(s)

Bexxar

Other Intervention Name(s)

Iodine I 131 tositumomab

Intervention Description

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.

Intervention Type

Drug

Intervention Name(s)

Low Dose Methotrexate

Intervention Description

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.

Primary Outcome Measure Information:

Title

Rate of Early Onset HAMA (Human Anti-mouse Antibody) Conversion Following Treatment

Description

Time Frame

7 weeks

Secondary Outcome Measure Information:

Title

Percentage of Participants That Respond to Treatment

Description

Time Frame

2 years

Title

The Percentage of Participants Alive at 2 Years

Description

Overall survival was examined at 2 years

Time Frame

2 years

Title

Median Progression Free Survival (PFS) Time

Description

The median time patients survived without progression.

Time Frame

2 Years

Title

Number of Participants That Experienced SAEs During Treatment.

Time Frame

Up to week 13

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Mark Kaminski, M.D.

Organizational Affiliation

University of Michigan

Official's Role

Principal Investigator

Facility Information:

Facility Name

University of Michigan

City

Ann Arbor

State/Province

Michigan

ZIP/Postal Code

48109

Country

United States

12. IPD Sharing Statement

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

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