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Phase II Multicenter Study of CVP Followed by Iodine-131 Anti-B1 Antibody for Subjects With Untreated Low-Grade Non Hodgkin's Lymphoma.

Phase 2
18 Years
Not Enrolling
Lymphoma, Non-Hodgkin

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Trial Information

Phase II Multicenter Study of CVP Followed by Iodine-131 Anti-B1 Antibody for Subjects With Untreated Low-Grade Non Hodgkin's Lymphoma.

This is a phase II, open-label, multicenter study of the efficacy and safety sequential
administration of cycolophosphamide, vacristine, and prednisone (CVP) x6 cycles followed by
tositumomab and iodine I 131 tositumomab for previously untreated subjects with low-grade
Non-Hodgkin's Lymphoma (NHL). CVP will be repeated every 21 days for a total of six cycles.
tositumomab and iodine I 131 tositumomab will begin within 56 days following the first day
of the sixth cycle of CVP. Subjects will undergo two dosing phase for the tositumomab and
iodine I 131 tositumomab therapy. In the first phase, "dosimetric dose", patients will
receive an infusion of unlabeled Anti-B1 Antibody (450mg) over 60 minutes followed by a 30
minute infusion (including a 10-minutes flush) of Anti-B1 (35mg) containing 5mCi of
Iodine-131. Whole body gamma camera scans will be obtained on Day 0; Day 2, 3, or 4 and Day
6 or 7 following the dosimetric dose. Using the dosimetric data from three time points, a
patient-specific dose of Iodine-131 will be calculated to deliver the desired total body
dose of radiotherapy. In the second phase, termed the "therapeutic dose", patients will
receive 60-minute infusion of unlabeled Anti-B1 Antibody (450 mg) followed by a 30-minute
infusion (including a 10-minute flush) of 35 mg Anti-B1 Antibody labeled with the subjects
-specific dose of Iodine-131 calculate to deliver a 75cGy total body radiation dose.
Subjects who have platelet counts of 100,000-149,999 cells/mm3 will receive 65 cGy; obese
patients will be dosed base upon 137% of their lean body mass. Subjects will be treated with
saturated solution potassium iodide (SSKI), Lugol's solution, or potassium iodide tablets
starting at least 24 hours prior to the first infusion of the tositumomab and iodine I 131
tositumomab (i.e., the dosimetric dose) and continuing for 14 days following the least
infusion of tositumomab and iodine I 131 tositumomab (i.e., the therapeutic dose).

Inclusion Criteria:

- Subjects must have a histologically confirmed initial diagnosis of low-grade
non-Hodgkin's B-cell lymphoma according to the International Working Formulation
(IWF) (32) (i.e., small lymphocytic with or without plasmacytoid differentiation;
follicular small cleaved cell; or follicular, mixed small cleaved and large cell).

- Subjects must have Ann Arbor Stage III, Stage IV, or bulky Stage II disease at
diagnosis. Bulky Stage II is defined as a mediastinal mass greater than one-third of
the maximum chest diameter, or any other mass greater than or equal to 10 cm in
maximum diameter.

- Subjects must have evidence that their tumor tissue expresses the CD20 antigen.
Immunoperoxidase stains of paraffin-embedded tissue showing positive reactivity with
L26 antibody or immunoperoxidase stains of frozen tissue showing positive reactivity
with Anti B1 Antibody (Coulter Clone®) or similar commercially available CD20
antibody or evidence of CD20 positivity by flow cytometry are acceptable evidence of
CD20 positivity. Testing of tumor tissue from any time in the course of the
patient's disease is acceptable.

- Subjects must have a performance status of at least 60% on the Karnofsky Performance
Scale and an anticipated survival of at least 3 months.

- Subjects must have an ANC≥1500 cells/mm3 and a platelet count ≥100,000 cells/mm3
within 14 days of study enrollment. These blood counts must be sustained without
support of hematopoietic cytokines or transfusion of blood products.

- Subjects must have adequate renal function (defined as serum creatinine <1.5 times
the upper limit of normal) and hepatic function (defined as total bilirubin <1.5
times the upper limit of normal and AST <5 times the upper limit of normal) within 14
days of study enrollment.

- Subjects must have bi-dimensionally measurable disease. At least one lesion must be
≥2.0x2.0 cm by computerized tomography scan.

- Subjects must be at least 18 years of age.

- Subjects of childbearing potential must have a negative serum pregnancy test within 7
days prior to study enrollment.

- Subjects must give written informed consent and sign an IRB-approved informed consent
form prior to study enrollment.

Exclusion Criteria:

- Subjects who have received prior chemotherapy, biologic therapy, steroids, or
radiation therapy as treatment for their NHL.

- Subjects with active obstructive hydronephrosis.

- Subjects with New York Heart Association class III or IV heart disease or other
serious illness that would preclude evaluation.

- Subjects with prior malignancy other than lymphoma, except for adequately treated
skin cancer, in situ cervical cancer, or other cancer for which the patient has been
disease-free for 5 years. Patients who have been disease-free of another cancer for
greater than 5 years must be carefully assessed at the time of study entry to rule
out recurrent disease.

- Subjects with known HIV infection.

- Subjects who are HAMA positive.

- Subjects with known brain or leptomeningeal metastases.

- Subjects who are pregnant or breastfeeding. Males and females must agree to use a
contraceptive method from enrollment to 6 months after receiving Iodine 131 Anti B1

- Subjects with active infection requiring IV anti-infectives at the time of study

- Subjects with intermediate- or high-grade NHL.

Type of Study:


Study Design:

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Number of Participants (Par.) With Unconfirmed Response (Complete Response, Complete Response/Unconfirmed, or Partial Response), as Assessed by the Investigator

Outcome Description:

Par. with response include those with Complete Response (CR: complete resolution of all disease-related radiological abnormalities and the disappearance of all signs and symptoms related to the disease), Complete Response/unconfirmed (CRu: complete resolution of all disease-related symptoms; residual lymph node mass >1.5 centimeters in the greatest transverse diameter that has regressed by >75%, indeterminate bone marrow, are present), or Partial Response (PR: >=50% reduction in the sum of the products of the longest perpendicular diameters of all measurable lesions; no new lesions).

Outcome Time Frame:

Par. were evaluated until death/disease progression or for 2 years in Study BEX104514. Par. who completed 2 years in Study BEX104514 were followed in Study BEX104528 for up to 130 months. Data are included from Study BEX104514 and Study BEX104528.

Safety Issue:


Principal Investigator

GSK Clinical Trials

Investigator Role:

Study Director

Investigator Affiliation:



United States: Food and Drug Administration

Study ID:




Start Date:

February 2000

Completion Date:

February 2012

Related Keywords:

  • Lymphoma, Non-Hodgkin
  • Non-Hodgkin's Lymphoma
  • tositumomab and iodine I 131 tositumomab
  • Bexxar
  • cycolophosphamide, vacristine, and pednisone
  • Lymphoma
  • Lymphoma, Non-Hodgkin