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

NCT01389076 | Terminated Phase 2 Results DMC

• 2 other identifiers: UMCC 2010.098HUM00043235
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 1

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.

Conditions

Follicular Lymphoma

Keywords

Previously Untreated, Advanced-Stage, Follicular Lymphoma

Outcome Measures

Primary Outcomes (1)

• 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.

  7 weeks

Secondary Outcomes (4)

• Percentage of Participants That Respond to Treatment

  2 years

• The Percentage of Participants Alive at 2 Years

  2 years

• Median Progression Free Survival (PFS) Time

  2 Years

• Number of Participants That Experienced SAEs During Treatment.

  Up to week 13

Study Arms (1)

Treatment arm

EXPERIMENTAL

Low dose methotrexate and Bexxar

Drug: Bexxar; Drug: Low Dose Methotrexate

Interventions

Bexxar DRUG

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.

Also known as: Iodine I 131 tositumomab

Treatment arm

Low Dose Methotrexate DRUG

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.

Treatment arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Michigan Rogel Cancer Center: lead
• GlaxoSmithKline: collaborator

Study Sites (1)

University of Michigan

Ann Arbor, Michigan, 48109, United States

Location

MeSH Terms

Conditions

Lymphoma, Follicular

Interventions

tositumomab I-131; Methotrexate

Condition Hierarchy (Ancestors)

Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Limitations and Caveats

This trial was abandoned prematurely due to the withdrawal of Bexxar by the manufacturer and failure to find another supplier.

Results Point of Contact

• Title: Dr. Mark Kaminski, M.D.
• Organization: University of Michigan Comprehensive Cancer Center

mkaminsk@umich.edu

734-936-5310

Study Officials

• Mark Kaminski, M.D.

  University of Michigan

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 5, 2011
• First Posted: July 7, 2011
• Study Start: July 1, 2011
• Primary Completion: February 1, 2014
• Study Completion: June 1, 2016
• Last Updated: January 30, 2017
• Results First Posted: July 12, 2016

Record last verified: 2016-12

Locations

US (1)