RADIOIMMUNOTHERAPY CLINICAL TRIAL #2



Phase II Study of Iodine-131 Anti-B1 Antibody for Non-Hodgkin's Lymphoma Patients who have Previously Received Rituximab


Description and Study Design:
This is a single-arm, open-label, multi-center study of Iodine-131 Anti-B1 Antibody for the treatment of Non-Hodgkin's Lymphoma (NHL) patients who were previously treated with Rituximab antibody. The endpoints of this study are to determine the response rate, complete response rate, duration of response, time to progression, time to treatment failure, and safety profile of Iodine-131 Anti-B1 Antibody therapy in patients who have previously been treated with Rituximab.

Patients will receive two sequential doses of Anti-B1, the "dosimetric dose" and the "radioimmunotherapy dose". The dosimetric dose consists of an infusion of unlabeled Anti-B1 (450 mg) immediately followed by an infusion of Anti-B1 (35 mg) which has been trace labeled with five mCi of Iodine-131. The radiation dose to the whole body delivered by the dosimetric dose will be determined from radioactivity clearance data. Based upon tracer data calculations specific for each individual patient, a patient-specific radioimmunotherapy dose will be given consisting of an infusion of unlabeled Anti-B1 (450 mg) immediately followed by an infusion of 35 mg Anti-B1 including a patient-specific mCi of activity of 131-Iodine-Anti-B1 calculated to deliver a whole-body radiation dose of 75 cGy. Forty patients will receive study drug in this multi-center study.

ELIGIBILITY CRITERIA

Inclusion Criteria:
1. Patients must have a histologically confirmed diagnosis of low-grade non-Hodgkin's B-cell lymphoma {i.e., small lymphocytic, follicular small-cleaved or follicular mixed small-cleaved lymphoma}, low-grade lymphoma that has transformed to higher grade histology, or de novo follicular large cell lymphoma.

2. Patients must have evidence that their tumor tissue expresses the CD20 antigen. This will be done by staining paraffin-imbedded tissue with antibody known to bind to CD20.

3. Patients must have been previously treated with at least four doses of Rituximab at any time and failed to achieve an objective response or relapsed/progressed during treatment or following the completion of Rituximab.

4. Patients must have progressive disease [(at least a 25% increase in tumor size at one or more site(s) of disease, or new site(s) of disease)].

5. Patients must have an anticipated survival of at least three months , performance status of at least 60% on the Karnofsky scale, and be able to provide self care.

6. Patients must have an absolute granulocyte count of over 1,500/mm3 and a platelet count above 100,000/mm3 within seven days of study entry.

7. Patients must have normal renal function (creatinine < 1.5 X upper limit of normal) and hepatic function (bilirubin < 1.5 X upper limit of normal and transaminases (SGOT and SGPT) < 5 X upper limit of normal) within seven days of study entry.

8. Patients must have bi-dimensionally measurable disease with at least one lesion greater than or equal to 2 x 2 cm.

9. Patients must be at least 18 years of age.

10. Patients must give written informed consent and sign an approved informed consent form prior to study entry.

Exclusion Criteria:
1. Patients with more than an average of 25% of the marrow space involved by lymphoma in bone marrow biopsy specimens as assessed microscopically at study entry.

2. Patients with de novo intermediate or high grade lymphoma.

3. Patients who have received cytotoxic chemotherapy, radiation therapy, immunosuppressants, or cytokine treatment within FOUR weeks prior to study entry (six weeks for nitrosourea compounds) or who exhibit persistent clinical evidence of toxicity. The use of steroids must be discontinued at least 1 week prior to study entry.

4. Patients with prior hematologic stem cell transplant following high-dose chemotherapy or chemo/radiotherapy.

5. Patients with obstructive hydronephrosis.

6.Patients with evidence of active infection requiring intravenous antibiotics at the time of study entry.

7. Patients with New York Heart Association class 3 or 4 heart disease or other serious illness that would preclude evaluation.

8. Patients with prior malignancy other than lymphoma, except for adequately treated skin cancer, in situ cervical cancer, or other cancer for which patient has been disease-free for five years.

9. Patients with known HIV infection.

10. Patients with known brain or leptomeningeal metastases.

11. Patients who are pregnant or nursing. Patients of child-bearing potential must undergo a pregnancy test within seven days of study entry. Males and females must agree to use effective contraception for 6 months following the radioimmunotherapy dose.

12. Patients with previous allergic reactions to iodine. This does not include reactions to intravenous iodine-containing contrast materials.

13. Patients who previously received radioimmunotherapy.

14. Patients with progressive disease within one year of irradiation in a field previously irradiated with greater than 3500 cGy.

15. Patients who are HAMA-positive.

16. Patients who are on another protocol involving non-approved or approved anti-cancer drugs or biologics.

Required Documentation:

The following documentation needs to be submitted by mail and/or FAX for patient enrollment evaluation:

1. A copy of your original pathology report and any subsequent pathology reports. Please include any bone marrow biopsy reports.

2. A copy of any surgical reports related to your cancer diagnosis.

3. Chemotherapy records with start and stop dates.

4. Radiation therapy treatment summary (if applicable).

5. Your latest CT scan report. Copies of your previous CT scans must be available to us.

6. Recent bloodwork (especially CBC and chemistry panels).

7. Recent history and physical exam.

8. Send pathology slides (both stained and unstained) to Jeannette Saal for review and staining for CD20 reactivity by a pathologist here at Stanford Hospital. Our address is:

Stanford University Hospital
300 Pasteur Drive
Department of Radiation Oncology
Attn: Jeannette Saal, R.N. Room AO-48
Stanford, CA 94305-5302

Pricipal Investigator: Sandra J. Horning, M.D. - Medical Oncology
Investigators: S.J. Knox, Ph.D, M.D., M.L.Goris, Ph.D., M.D., Jennifer Lucas, M.D. and Steve Horwitz, M.D.
Contact Person: Jeannette Saal, R.N., Phone: (650) 725-1730, Fax: (650) 498-4093


Webmaster: Jeannette Saal jsaal@reyes.stanford.edu

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