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Phase II a Randomized Study of Iodine-131 Anti-b1 Antibody Versus Anti-b1 Antibody in Chemotherapy-relapsed/Refractory Low-grade or Transformed Low-grade Non-Hodgkin's Lymphoma (NHL)

Phase 2
18 Years
Not Enrolling
Lymphoma, Non-Hodgkin

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Trial Information

Phase II a Randomized Study of Iodine-131 Anti-b1 Antibody Versus Anti-b1 Antibody in Chemotherapy-relapsed/Refractory Low-grade or Transformed Low-grade Non-Hodgkin's Lymphoma (NHL)

This is a Phase II randomized, controlled, two-arm, open-label, multicenter study comparing
the safety and efficacy of tositumomab and iodine I 131 tositumomab to tositumomab for the
treatment of chemotherapy-relapsed or refractory low-grade or transformed low-grade B-cell

Treatment Arm A: Subject will undergo 2 phases of study. In the first phase, termed
"dosimetric dose", subjects will receive tositumomab (450 mg) followed by tositumomab (35
mg) that has been trace labeled with 5mCi) Iodine-131 tositumomab. 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 imaging time points, a subject-specific dose of
iodine I 131 tositumomab to deliver the desired total body dose of radiotherapy will be
calculated. In the second phase of the study, termed "therapeutic dose", subjects will
receive unlabeled tositumomab (450mg) followed by iodine tositumomab (35mg) labeled with
the subject-specific dose of iodine I-131 to deliver a whole body dose of 75 cGy to
subjects. Subjects with platelet counts of 100,001 - 149,999 cells/mm3, will receive 65
cGy and subjects who are obese will be doses based on 137% of their lean body mass.
Subjects will be treated with either saturated solution potassium iodide (SSKI), Lugol's
solution, or potassium iodide tablets starting at least 24 hours prior to the first infusion
of the Iodine-131 tositumomab (i.e., the dosimetric dose) and continuing for 14 days
following the last infusion of radiolabeled tositumomab (i.e., the therapeutic dose).

Treatment Arm B: Subjects will receive the same amount of unlabeled tositumomab (450 + 35
mg) administered over the same time-frame as Arm A on the study Days 0 and 7 (the day 7 dose
may be delayed but no longer than 14 days after the first dose).

Crossover treatment Arm B: Subjects in Arm B may crossover and receive Iodine-131
tositumomab following progression of their lymphoma if they still fulfill the protocol
inclusion exclusion criteria (except exclusion criteria#12) and are HAMA-negative.

Inclusion Criteria:

- Histologically confirmed low-grade or transformed NHL with evaluable, measurable

- Tumor had to express CD20 antigen

- One to three prior chemotherapy regimens

- Karnofsky performance score ≥60% and anticipated survival ≥3 months

- Absolute neutrophil count (ANC) >1500/mm3 and platelet count >100,000/mm3

- Adequate renal and hepatic function

- 18 years of age or older.

- Written informed consent and sign an IRB-approved Informed consent from prior to
study entry.

Exclusion Criteria:

- More than an average of 25% of the intratrabecular marrow space involved by lymphoma
in bone marrow biopsy specimens as assessed microscopically within 42 days of study
entry. Bilateral posterior iliac crest core biopsies are required if the percentage
of intratrabecular space involved exceeds 10% on a unilateral biopsy. The mean of
bilateral biopsies must be no more than 25%.

- Received cytotoxic chemotherapy, radiation therapy, immunosuppressants, or cytokine
treatment within FOUR weeks prior to study entry (6 weeks of 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.

- Have undergone prior stem cell transplant.

- Active obstructive hydronephrosis.

- Evidence of active infection requiring intravenous antibiotics at the time of study

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

- Prior malignancy other than lymphoma, except for adequately-treated skin cancer, in
situ cervical cancer, or other cancer for which subject has been disease-free for 5

- Known HIV infection.

- Known brain or leptomeningeal metastases.

- Pregnant or nursing. Subjects of childbearing potential must undergo pregnancy test
within 7 days of study entry and antibody is not to be administered until a negative
result is obtained. For those subjects in Arm B, the pregnancy test must be repeated
within 7 days of crossover. Male and female must agree to use effective contraception
for 6 months following the therapeutic dose, as applicable.

- Previous allergic reactions to iodine. This does not include reactions to intravenous
iodine-containing contrast materials.

- Previously given any monoclonal or polyclonal antibodies of any non-human species for
either diagnostic or therapeutic purpose. This includes engineered chimeric and
humanized antibodies.

- Previously received radioimmunotherapy .

- Progressive disease within one year of irradiation arising in a field that has been
previously irradiated with >3500 cGy.

- de novo intermediate or high-grade lymphoma.

- Received >3 chemotherapy regimens (different or identical agents).

Type of Study:


Study Design:

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

Outcome Measure:

Number of Participants (Par.) With Confirmed Response as Assessed by the Investigator

Outcome Description:

Responses had to be confirmed by 2 separate evaluations occurring >=4 weeks apart. Par. with confirmed 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), Clinical Complete Response (CCR: complete resolution of all disease-related symptoms; residual foci, thought to be residual scar tissue, 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:

Participants were evaluated for up to two years in Study BEX104515 and for up to 11.9 years in Study BEX104526.

Safety Issue:


Principal Investigator

GSK Clinical Trials

Investigator Role:

Study Director

Investigator Affiliation:



United States: Food and Drug Administration

Study ID:




Start Date:

September 1998

Completion Date:

April 2010

Related Keywords:

  • Lymphoma, Non-Hodgkin
  • Bexxar
  • Non-Hodgkin's Lymphoma
  • Tositumomab
  • Anti-B1 Antibody
  • Radioimmunotherapy
  • Iodine I-131
  • Iodine-131
  • Lymphoma
  • Lymphoma, Non-Hodgkin