A Phase II Trial of Combined Weekly Bortezomib and Tositumomab I-131 in Patients With Relapsed or Refractory Follicular Non-Hodgkin's Lymphoma
Condition: Follicular Lymphoma
MeSH terms: Lymphoma
Intervention: Bortezomib and Tositumomab I-131
Intervention MeSH terms: Bortezomib; Tositumomab I-131
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 1.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Non-Hodgkin's Lymphoma; Follicular Non-Hodgkin's Lymphoma; Lymphoma

Summary:

      The purpose of this study is to determine what dose of bortezomib in combination with
      tositumomab I-131 is tolerable whether bortezomib and Tositumomab I-131 are effective in the
      treatment of relapsed or refractory non-hodgkin's lymphoma (NHL). Both agents are effective
      in treating relapsed and refractory NHL. Administer of the agents together may sensitize the
      cells to the radiation from Tositumomab I-131.
    

Eligibility criteria:

        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.