A Multi-Center Study to Examine the Pharmacokinetics, Whole Body and Organ Dosimetry, and Biodistribution of Fission-Derived Iodine I 131 Tositumomab for Patients With Previously Untreated or Relapsed Follicular or Transformed Follicular Non-Hodgkin's Lymphoma
Inclusion Criteria
Inclusion criteria
1. At least 18 years of age
2. A histologically confirmed diagnosis of the following:
Follicular lymphoma, Grade 1, 2, or 3 or diffuse large cell lymphoma concurrent with
or following the diagnosis of follicular lymphoma (World Health Organization/Revised
European-American Lymphoma [WHO/REAL] classification).
International Working Formulation histological equivalents included:
Follicular, small-cleaved; Follicular, mixed small-cleaved and large-cell; Follicular
large-cell; or Transformed diffuse large-cell lymphoma following or concurrent with a
diagnosis of follicular lymphoma.
3. Stage III or IV disease at the time of study entry (based on Ann Arbor Staging
Classification)
4. Previously untreated or recurrent lymphoma after no more than 4 prior qualifying
therapy regimens; steroids alone, as treatment for lymphoma, not considered a
treatment regimen
5. Performance status of at least 70% on the Karnofsky Performance Scale and an
anticipated survival of at least 3 months.
6. Bi dimensionally measurable disease with at least one lesion measuring greater than
or equal to 2.0 cm x 2.0 cm (greater than or equal to 4.0 cm2) by computed tomography
(CT) scan
7. Absolute B lymphocyte count (as determined by CD19 reactivity [flow cytometric
determination of CD19+ B lymphocyte count]) of 30 to 350 cell/mm3 within 21 days
prior to study enrollment
8. Absolute neutrophil count greater than or equal to 1500 cells/mm3; platelet count
greater than or equal to 150,000/mm3; and hemoglobin greater than or equal to 10 g/dL
within 21 days prior to study enrollment; blood products and/or growth factors not
taken within 4 weeks prior to blood draw
9. Adequate renal function, defined as serum creatinine <1.5 x upper limit of normal
(ULN), and hepatic function, defined as total bilirubin <1.5 x ULN and aspartate
transaminase (AST) <5 x ULN, within 21 days of study enrollment
10. HAMA negative within 21 days prior to study enrollment
11. Signed IRB approved consent form prior to any study-specific procedures being
implemented
Exclusion criteria
1. Greater than 25% of the intratrabecular marrow space involved by lymphoma in bone
marrow biopsy specimens as assessed microscopically within 90 days of study
enrollment; a unilateral bone marrow biopsy was adequate; marrow core was greater
than or equal to 2.0 cm in length
2. Prior chemotherapy, biologic therapy, steroids, or radiation therapy as treatment for
NHL within 28 days prior to study enrollment; subjects receiving low doses of
steroids for non neoplastic disease acceptable to enter this study ("Low dose
steroids" was defined as less than or equal to 10 mg of prednisone or equivalent per
day.)
3. Prior rituximab therapy within 120 days prior to study enrollment
4. Prior radioimmunotherapy
5. Prior splenectomy
6. Splenomegaly defined as spleen mass greater than 700 grams, where splenic mass was
defined as follows:
Spleen mass = л(X x Y x Z)/6 Where X and Y are the greatest perpendicular diameters
in cm on any single CT scan slice, and Z is the number of CT scan slices upon which
the spleen is visible times the slice thickness in cm
7. Bulky disease as defined as any uni-dimensional measurement of lymphomatous mass
exceeding 7 cm
8. Prior malignancy other than lymphoma, except for adequately treated skin cancer, in
situ cervical cancer, or other cancer for which the subject had a generally accepted
risk of recurrence less than 20%
9. Central nervous system involvement by lymphoma
10. Evidence of active infection requiring IV antibiotics at the time of study enrollment
11. Known human immunodeficiency virus (HIV) infection
12. New York Heart Association Class III or IV heart disease or other serious illness
that would preclude evaluation.
13. Active obstructive hydronephrosis
14. Evidence of clinically significant ascites or pleural effusion observed on screening
physical examination or baseline CT scan
15. Prior myeloablative therapy
16. History of failed stem cell collection
17. Pregnant or nursing subjects (Subjects of childbearing potential had to have a
negative serum pregnancy test within 21 days of study enrollment. Males and females
of childbearing age had to agree to use effective contraception for up to 12 months
after the radioimmunotherapy.)