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

NCT00989664 | Completed Phase 2 Results

• 1 other identifier: 104504
• Study Type: interventional
• Target: 60
• Locations: 0 countries
• Sites: N/A

Brief Summary

The results from Phase 1/2 (RIT-I-000) and Phase 2 (RIT-II-001) studies of Tositumomab and Iodine I 131 Tositumomab (TST/I-131 TST) demonstrated that TST/ I-131 TST produced a high response rate in patients with chemotherapy-relapsed/refractory, low-grade or transformed low-grade Non-Hodgkin's Lymphoma (NHL). On the basis of these results this study was designed to compare the efficacy of TST/ I-131 TST to the last qualifying chemotherapy regimen in patients with chemotherapy-refractory, low-grade or transformed low-grade NHL.

Conditions

Lymphoma, Non-Hodgkin

Keywords

non-Hodgkin's Lymphoma; radioimmunotherapy; NHL; Bexxar; lymphoma; Tositumomab

Outcome Measures

Primary Outcomes (2)

• 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

  Par. with response are those with complete response (CR; complete resolution of all disease-related radiological abnormalities and the disappearance of all signs/symptoms related to disease), complete response unconfirmed (CRu; meets characteristics of CR, except the nodal size hasn't regressed sufficiently, or there is indeterminate bone marrow), or partial response (PR; \>=50% reduction in the sum of the products of the longest perpendicular diameters of all measurable lesions with no new lesions). Participants' LQCR was used as a comparator for subsequent treatment with Iodine I 131TST.

  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

• 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

  Duration of response is defined as the time from the first documented response (for par. with complete response, complete response unconfirmed, or partial response) until disease progression (DP). DP is defined as a \>=25% increase from the nadir value (lowest laboratory value recorded following administration of the study medication) of the sum of the products of the longest perpendicular diameters of all measurable lesions or the appearance of any new lesion. Individual lesions must be \>2 centimeters (cm) in diameter by radiographic evaluation or \>1 cm in diameter by physical examination.

  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 Outcomes (20)

• 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

  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

  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

  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

  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

  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

Study Arms (1)

open-label single arm

EXPERIMENTAL

Tositumomab and Iodine-131 Tositumomab radioimmunotherapy for chemotherapy-refractory low-grade B-cell lymphomas and low-grade lymphomas that have transformed to higher grade histologies.

Biological: Tositumomab and Iodine I 131 Tositumomab

Interventions

Tositumomab and Iodine I 131 Tositumomab BIOLOGICAL

Dosimetric Dose: 450 mg of TST infused over 70 minutes (inclusive of a 10-minute flush) immediately followed by I-131 TST (35 mg of TST, of which 1-2 mg had been labeled with 5 mCi of Iodine-131) infused over 30 minutes (inclusive of a 10-minute flush). Therapeutic Dose: 7 to 14 days after the dosimetric dose, 450 mg of TST infused over 70 minutes (inclusive of a 10-minute flush) immediately followed by I-131 TST (35 mg of TST labeled with enough Iodine-131 to administer the specified whole body radiation dose determined for the subject) infused over 30 minutes (inclusive of a 10-minute flush). The desired total body dose was 65 cGy for subjects with a baseline platelet count of 100,001-149,999/mm3 and 75 cGy for patients with a baseline platelet count ≥150,000/mm3. Obese patients received an attenuated dose by not including subject mass over 137% of their calculated lean body mass in their calculated lean body mass in the dose calculation.

open-label single arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• GlaxoSmithKline: lead

Related Publications (1)

• Kaminski MS, Zelenetz AD, Press OW, Saleh M, Leonard J, Fehrenbacher L, Lister TA, Stagg RJ, Tidmarsh GF, Kroll S, Wahl RL, Knox SJ, Vose JM. Pivotal study of iodine I 131 tositumomab for chemotherapy-refractory low-grade or transformed low-grade B-cell non-Hodgkin's lymphomas. J Clin Oncol. 2001 Oct 1;19(19):3918-28. doi: 10.1200/JCO.2001.19.19.3918.

  PMID: 11579112 BACKGROUND

Related Links

• Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.

MeSH Terms

Conditions

Lymphoma, Non-Hodgkin; Lymphoma

Interventions

tositumomab I-131

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR
• Expanded Access: Yes

Study Record Dates

• First Submitted: October 1, 2009
• First Posted: October 5, 2009
• Study Start: November 1, 1996
• Primary Completion: January 1, 2004
• Study Completion: September 1, 2008
• Last Updated: December 13, 2016
• Results First Posted: April 10, 2012

Record last verified: 2016-10

Data Sharing

• IPD Sharing: Will share