RADIOIMMUNOTHERAPY CLINICAL TRIAL #1



A randomized controlled study to compare the activity and safety of 131-Iodine-radiolabeled Anti-B1 (Murine) with unlabeled anti-B1 (Murine) in chemotherapy-refractory low grade NHL.


Description and Study Design:
This is a randomized study designed to compare the efficacy and safety of 131-Iodine-labeled anti-CD20 (131-I-anti-B1) with unlabeled anti-B1 as therapy for low-grade B-cell lymphoma. There will be two treatment arms, unlabeled and radiolabeled antibody. Patients receiving unlabeled antibody will be treated on an outpatient basis. This will involve two infusions of antibody requiring up to 6 hours of time. Patients randomized to receive radiolabeled antibody will be admitted for one to three days. As we expect that the unlabeled anti-B1 will be less efficacious, we have included a unilateral crossover where those initially treated with the unlabeled antibody will receive the radiolabeled version at time of disease progression and serve as their own control population.

The primary goals of this trial are to:
1) To determine the contribution of radiolabeling in anti-B1 therapy as defined by response rates, response durations, time to next treatment and survival following therapy, and,

2) To assess the safety profile of 131-I-anti-CD20 therapy as compared to unlabeled anti-B1.

ELIGIBILITY CRITERIA

Inclusion Criteria:
1. Patients must have a histologically confirmed diagnosis of low-grade non-Hodgkin's B-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 one chemotherapy regimen that included an anthracycline, an anthracenedione or an alkylating agent. Patients who have received greater than 3 different chemotherapy regimens are excluded.

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 within 12 months of their last chemotherapy)].

5. Patients must have an anticipated survival of at least three months 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 less than 2.0 mg/dL) and hepatic function (bilirubin less than 2.0 mg/dL) within seven days of study entry.

8. Patients must have valuable, 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.

4. Patients who have received greater than 3 different chemotherapeutic regimens.

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

6. Patients with obstructive hydronephrosis.

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

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

9. 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.

10. Patients with known HIV infection.

11. Patients with known brain or leptomeningeal metastases.

12. 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 during the study.

13. Patients with previous allergic reactions to iodine. This does not include i.v. reactions to iodine-containing contrast materials.

14. Patients who previously received radioimmunotherapy.

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

16. Patients who were previously given any monoclonal or polyclonal antibodies of any foreign species for either diagnostic or therapeutic purposes. This includes engineered chimeric and humanized antibodies.

17. 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

Investigators: S.J. Knox, Ph.D, M.D., R. Levy, M.D., M.L.Goris, Ph.D., 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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