A Phase II Trial of Combined Weekly Bortezomib and Tositumomab I-131 in Patients With Relapsed or Refractory Follicular Non-Hodgkin's Lymphoma

U.S. FDA Resources

Estimated Enrollment:	20
Study Start Date:	May 2007
Study Completion Date:	September 2008
Primary Completion Date:	September 2008 (Final data collection date for primary outcome measure)

Inclusion Criteria:

• Previously treated or relapsed follicular lymphoma. One prior therapy required.
• Bi-dimensionally measurable disease with at least one lesion measuring > 2.0 X 2.0cm by CT scan or evaluable disease.
• CD20+ at time of diagnosis or subsequently.
• Platelet count > 100,000/uL, ANC > 1000/uL.
• Transaminases less than two-fold normal range.
• Adequate renal function defined as <1.5 X upper limit of normal
• HAMA negative
• ECOG performance status 0, 1, 2.
• Female subject is either post-menopausal or surgically sterilized or willing to use an acceptable method of birth control (i.e., a hormonal contraceptive, intra-uterine device, diaphragm with spermicide, condom with spermicide, or abstinence) for the duration of the study.
• Male subject agrees to use an acceptable method for contraception for the duration of the study.
• Negative Hepatitis profile screening

Exclusion Criteria:

• Myocardial infarction within 6 months prior to enrollment or has New York Heart Association (NYHA) Class III or IV heart failure (see section 8.4), uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities. Prior to study entry, any ECG abnormality at Screening has to be documented by the investigator as not medically relevant.
• Patient has hypersensitivity to boron or mannitol.
• Greater than 25% of the intratrabecular marrow space involved by lymphoma in bone marrow biopsy specimens
• Hypocellular bone marrow (≤15% cellularity or marked reduction in bone marrow precursors).
• Prior myeloablative therapy.
• History of failed stem cell collection.
• Prior radiotherapy to fields encompassing more than 25% of the blood-forming marrow.
• Prior chemotherapy, biologic therapy, radiation therapy or steroid therapy for NHL within three weeks prior to screening procedures. Six weeks for nitrosureas. Subjects receiving low doses of steroids for non-neoplastic indications may enter the study ("low dose steroids" is defined as ≤10 mg of prednisone or equivalent per day).
• Prior Radioimmunotherapy or bortezomib.
• Prior malignancy other than lymphoma, except for adequately treated basal cell or squamous cell skin cancer, in situ uterine cervical cancer, or other cancer for which the subject has been disease-free for five years.
• Evidence of active infection requiring intravenous antibiotics at the time of study enrollment.
• Known HIV infection.
• Known brain or leptomeningeal metastases.
• Active obstructive hydronephrosis.
• Known Type I hypersensitivity or anaphylactic reactions to murine proteins or any component of the Iodine I 131 tositumomab therapeutic regimen.
• Female subject is pregnant or breast-feeding. Confirmation that the subject is not pregnant must be established by a negative serum pregnancy test result obtained during screening. Pregnancy testing is not required for post-menopausal or surgically sterilized women.
• Patient has received other investigational drugs with 14 days before enrollment
• Serious medical or psychiatric illness likely to interfere with participation in this clinical study.
• Patient has Grade 2 peripheral neuropathy within 14 days before enrollment.

Rush University Medical Center

GlaxoSmithKline

Millennium Pharmaceuticals, Inc.

Non-Hodgkin's Lymphoma Follicular Non-Hodgkin's Lymphoma Lymphoma

Lymphoma Lymphoma, Follicular Lymphoma, Non-Hodgkin Neoplasms by Histologic Type Neoplasms Lymphoproliferative Disorders Lymphatic Diseases Immunoproliferative Disorders Immune System Diseases Iodine-131 anti-B1 antibody

Bortezomib Antibodies, Monoclonal Antineoplastic Agents Therapeutic Uses Pharmacologic Actions Immunologic Factors Physiological Effects of Drugs Protease Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action