Pivotal Study of Iodine I 131 Tositumomab for Chemotherapy-refractory Low-grade or Transformed Low-grade B-cell Non-Hodgkin's Lymphoma

• Register: ClinicalTrials.gov
• Last refreshed on: 17 October 2012
• Main ID: NCT00989664
• Date of registration: 01/10/2009
• Primary sponsor: GlaxoSmithKline
• Public title: Pivotal Study of Iodine I 131 Tositumomab for Chemotherapy-refractory Low-grade or Transformed Low-grade B-cell Non-Hodgkin's Lymphoma
• Scientific title: Multicenter, Pivotal Phase III Study of Iodine-131 Anti-B1 Antibody (Murine) Radioimmunotherapy for Chemotherapy Refractory Low Grade B Cell Lymphomas and Low Grade Lymphomas That Have Transformed to Higher Grade Histologies
• Date of first enrolment: November 1996
• Target sample size: 60
• Recruitment status: Completed
• URL: http://clinicaltrials.gov/show/NCT00989664
• Study type: Interventional
• Study design: Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Contacts

• Name: GSK Clinical Trials
• Affiliation: GlaxoSmithKline

Key inclusion & exclusion criteria

Inclusion Criteria:

- Male and female subjects =18 years of age with histologically confirmed at initial
diagnosis, previously treated (at least 2 prior chemotherapy regimens), low-grade NHL
or low-grade lymphoma that had transformed to intermediate- or high-grade histology.

Exclusion Criteria:

- Subjects with 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 intratrebecular space involved exceeds 10% in a
unilateral biopsy. The mean of bilateral biopsies must be no more than 25%.

- Cytotoxic chemotherapy, radiation therapy, immunosuppressants, or cytokine treatment
within 4 weeks prior to study entry or persistent clinical evidence of toxicity.

- Prior stem cell transplant.

- Active obstructive hydronephrosis.

- Evidence of active infection requiring intravenous (IV) antibiotics at the time of
study entry.

- 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 the subject has been disease-free for
5 years.

- Known HIV infection.

- Known brain or leptomeningeal metastases.

- Subjects who are pregnant or nursing.

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

- Prior exposure to monoclonal or polyclonal antibodies of any non-human species for
either diagnostic or therapeutic purposes, including engineered chimeric and
humanized antibodies.

- Prior radioimmunotherapy.

- Progressive disease within 1 year of irradiation arising in a field that has been
previously irradiated with >3500 cGy.

- Current use of either approved or non-approved (through another protocol) anti-cancer
drugs or biologics

- De novo intermediate- or high-grade lymphoma.



Age minimum: 18 Years
Age maximum: N/A
Gender: Both

Health Condition(s) or Problem(s) studied

Lymphoma, Non-Hodgkin

Intervention(s)

Biological: Tositumomab and Iodine I 131 Tositumomab

Primary Outcome(s)

Duration of Response for Par. Receiving TST and I 131 TST With a Response >=30 Days Versus the Number of Par. With a Response >=30 Days After Their LQCR, as Assessed by the MIRROR Panel [Time Frame: Participants were evaluated for up to 99.1 months in Study 104504 or were followed in the long-term follow-up study for up to 141.5 months]

Number of Participants (Par.) Receiving TST and I 131 TST With a Response >=30 Days Versus Par. With a Response >=30 Days After Their Last Qualifying Chemotherapy Regimen (LQCR), Masked Independent Randomized Radiology and Oncology Review (MIRROR) Panel [Time Frame: Participants were evaluated for up to 99.1 months in Study 104504 or were followed in the long-term follow-up study for up to 141.5 months]

Secondary Outcome(s)

Number of Participants Who Were Negative for Human Anti-murine Antibodies (HAMA) at Baseline (Before Receiving the Dosimetric Dose) But Positive or Negative After Receiving the Dosimetric Dose [Time Frame: HAMA was measured at baseline; Day5; Weeks 7, 17, 25; and then every 12 months while in study BEX104526. Participants were evaluated for up to 99.1 months in Study 104504 or were followed in the long-term follow-up study for up to 141.5 months]

Number of Participants With an Infection for Which Anti-infectives Were Administered [Time Frame: Participants were evaluated for up to 99.1 months in Study 104504 or were followed in the long-term follow-up study for up to 141.5 months]

Number of Participants With Any Confirmed Response (CR, CCR, or PR), Confirmed CR, Confirmed CCR, Confirmed CR+CCR, and Confirmed PR, as Assessed by Investigator [Time Frame: Participants were evaluated for up to 99.1 months in Study 104504 or were followed in the long-term follow-up study for up to 141.5 months]

Number of Participants With Any Uncofirmed Response (CR, Clinical Complete Response [CCR], or PR), CR, CCR, CR+CCR, and PR), as Assessed by the Investigator [Time Frame: Participants were evaluated for up to 99.1 months in Study 104504 or were followed in the long-term follow-up study for up to 141.5 months]

Number of Participants With Hypothyroidism Prior to Therapy and After the Therapeutic Dose [Time Frame: Participants were evaluated for up to 99.1 months in Study 104504 or were followed in the long-term follow-up study for up to 141.5 months]

Number of Participants With Responses of CR, CCR, CR+CCR, and PR Following TST and I 131 TST and Following the LQCR, as Assessed by the Investigator [Time Frame: Participants were evaluated for up to 99.1 months in Study 104504 or were followed in the long-term follow-up study for up to 141.5 months]

Number of Participants With the Indicated Adverse Events (AE) Related to Study Drug Experienced by at Least 5% of Participants [Time Frame: Participants were evaluated for up to 99.1 months in Study 104504 or were followed in the long-term follow-up study for up to 141.5 months]

Number of Participants With the Indicated Fatal SAEs Related to Study Drug [Time Frame: Participants were evaluated for up to 99.1 months in Study 104504 or were followed in the long-term follow-up study for up to 141.5 months]

Number of Participants With the Indicated Fatal Serious Adverse Events (SAE) Unrelated to Study Drug [Time Frame: Participants were evaluated for up to 99.1 months in Study 104504 or were followed in the long-term follow-up study for up to 141.5 months]

Number of Participants With the Indicated Grade 3 or Grade 4 AEs Experienced by at Least 5% of Participants [Time Frame: Participants were evaluated for up to 99.1 months in Study 104504 or were followed in the long-term follow-up study for up to 141.5 months]

Number of Participants With the Indicated Grade 3 or Grade 4 AEs Related to Study Drug and Experienced by at Least 5% of Participants [Time Frame: Participants were evaluated for up to 99.1 months in Study 104504 or were followed in the long-term follow-up study for up to 141.5 months]

Number of Participants With the Indicated Grade 3 or Grade 4 Hematologic Toxicities [Time Frame: Participants were evaluated for up to 99.1 months in Study 104504 or were followed in the long-term follow-up study for up to 141.5 months]

Number of Participants With the Indicated Primary Cause of Death [Time Frame: Participants were evaluated for up to 99.1 months in Study 104504 or were followed in the long-term follow-up study for up to 141.5 months]

Number of Participants With the Indicated SAEs Related to Study Drug [Time Frame: Participants were evaluated for up to 99.1 months in Study 104504 or were followed in the long-term follow-up study for up to 141.5 months]

Number of Participants With the Indicated Time to Death From the Last Dose of Study Drug [Time Frame: Participants were evaluated for up to 99.1 months in Study 104504 or were followed in the long-term follow-up study for up to 141.5 months]

Number of Participants With the Indicated Type of Infection [Time Frame: Participants were evaluated for up to 99.1 months in Study 104504 or were followed in the long-term follow-up study for up to 141.5 months]

Overall Survival [Time Frame: Participants were evaluated for up to 99.1 months in Study 104504 or were followed in the long-term follow-up study for up to 141.5 months]

Time to HAMA Positivity From the First Dosimetric Dose [Time Frame: HAMA was measured at baseline; Day5; Weeks 7, 17, 25; and then every 12 months while in study BEX104526. Participants were evaluated for up to 99.1 months in Study 104504 or were followed in the long-term follow-up study for up to 141.5 months]

Time to Progression of Disease or Death, as Assessed by the Investigator [Time Frame: Participants were evaluated for up to 99.1 months in Study 104504 or were followed in the long-term follow-up study for up to 141.5 months]

Time to Treatment Failure, as Assessed by the Investigator [Time Frame: Participants were evaluated for up to 99.1 months in Study 104504 or were followed in the long-term follow-up study for up to 141.5 months]

Secondary ID(s)

104504

RIT-II-004

Source(s) of Monetary Support

Please refer to primary and secondary sponsors