Clinical Trial: Study of Iodine 131 Anti B1 Antibody for 1st or 2nd Relapsed Indolent B-Cell Lymphomas or B-Cell Lymphomas That Have Transformed to a More Aggressive Histology

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: Phase II Study of Iodine 131 Anti B1 Antibody for 1st or 2nd Relapsed Indolent B-Cell Lymphomas or B-Cell Lymphomas That Have Transformed to a More Aggressive Histology

Brief Summary:

This is a single-arm, open-label study of Iodine 131 Anti B1 Antibody for the treatment of 1st or 2nd relapsed indolent B cell lymphomas or B cell lymphomas that have transformed to a more aggressive histology. The primary endpoint of the study is to determine the response rate. Secondary endpoints of the study is to determine the duration of response, time to progression, time-to-treatment failure, safety, and survival.

Forty patients will receive therapy on this study at the 2 clinical sites. Patients will undergo 2 phases of the study. In the first phase, termed the "dosimetric dose", patients will receive an infusion of unlabeled Anti B1 Antibody (450 mg) over 70 minutes (including a 10 minute flush) immediately followed by a 30 minute infusion (including a 10 minute flush) of Anti B1 Antibody (35 mg) which has been trace-labeled with 5 mCi of Iodine 131. Whole body gamma camera scans will be obtained on 1) Day 0; 2) Day 2, 3, or 4; and 3) Day 6 or 7 following the dosimetric dose. Using the dosimetric data from the 3 imaging timepoints, a patient-specific dose of Iodine 131 Anti B1 Antibody to deliver the desired total body dose of radiotherapy will be calculated. In the second phase, termed the "radioimmunotherapeutic dose", patients will receive a 70 minute infusion (including a 10 minute flush) of unlabeled Anti B1 Antibody (450 mg) immediately followed by a 30 minute infusion (including a 10 minute flush) of 35 mg Anti B1 Antibody labeled with the patient-specific dose of Iodine 131 to deliver a whole body dose of 75 cGy to patients with no hematologic risk factors. Patients who have platelet counts of 100,001-149,999 cells/mm3 will receive 65 cGy and patients who are obese will be dosed based upon 137% of their lean body mass (see Appendix A). Patients will be treated with either saturated solution potassium iodide (SSKI), Lugol's solution, or

Detailed Summary:
Sponsor: GlaxoSmithKline

Current Primary Outcome:

  • Number of Participants (Par.) With Response as Assessed by the Investigator [ Time Frame: Par. were evaluated until death/disease progression or 2 years in Study BEX104505. Par. who completed 2 years in BEX104505 were followed in study BEX104528 for up to 125 months. Data are included from both Study BEX104505 and Study BEX104528. ]
    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), 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).
  • Number of Participants With Confirmed Response as Assessed by the Investigator [ Time Frame: Par. were evaluated until death/disease progression or 2 years in Study BEX104505. Par. who completed 2 years in BEX104505 were followed in study BEX104528 for up to 125 months. Data are included from both Study BEX104505 and Study BEX104528. ]
    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 measurab

    Original Primary Outcome: The primary endpoint of the study is to determine the response rate [ Time Frame: Subjects followed for life or 10 years when entered into Study 104528 ]

    Current Secondary Outcome:

    • Duration of Response for All Confirmed Responders (CR, CCR, or PR) as Assessed by the Investigator [ Time Frame: Par. were evaluated until death/disease progression or 2 years in Study BEX104505. Par. who completed 2 years in BEX104505 were followed in study BEX104528 for up to 125 months. Data are included from both Study BEX104505 and Study BEX104528. ]
      Responses had to be confirmed by 2 separate evaluations occurring >=4 weeks apart. Duration of response is defined as the time from the first documented response until disease progression. Disease progression is defined as a >=25% increase from the nadir value 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 cm in diameter by radiographic evaluation or >1 cm in diameter by physical examination.
    • Time to Progression of Disease or Death as Assessed by the Investigator [ Time Frame: Par. were evaluated until death/disease progression or 2 years in Study BEX104505. Par. who completed 2 years in BEX104505 were followed in study BEX104528 for up to 125 months. Data are included from both Study BEX104505 and Study BEX104528. ]
      Time to progression or progression-free survival is defined as the time from the dosimetric dose to the first documented occurrence of disease progression or death. Disease progression is defined as a >=25% increase from the nadir value of the sum of the products of the longest perpendicular diameters of all measurable lesions or the appearance of any new lesion. New lesions must be greater than 2 x 2 centimeters (cm) in diameter by radiographic evaluation or greater than 1 cm in diameter by physical examination.
    • Time to Treatment Failure as Assessed by the Investigator [ Time Frame: Par. were evaluated until death/disease progression or 2 years in Study BEX104505. Par. who completed 2 years in BEX104505 were followed in study BEX104528 for up to 125 months. Data are included from both Study BEX104505 and Study BEX104528. ]
      Time to treatment failure is defined as the length of time from the date of enrollment to the first incidence of treatment withdrawal, study removal, progression, and/or alternative therapy for the participant's lymphoma, or death.
    • Overall Survival [ Time Frame: Par. were evaluated until death/disease progression or 2 years in Study BEX104505. Par. who completed 2 years in BEX104505 were followed in study BEX104528 for up to 125 months. Data are included from both Study BEX104505 and Study BEX104528. ]
      Overall survival is defined as the time from the treatment start date to the date of death from any cause.
    • Number of Participants With the Indicated Adverse Events (AE) Possibly or Probably Related to Study Drug and Experienced by at Least 5% of Participants [ Time Frame: Par. were evaluated until death/disease progression or 2 years in Study BEX104505. Par. who completed 2 years in BEX104505 were followed in study BEX104528 for up to 125 months. Data are included from both Study BEX104505 and Study BEX104528. ]
      An AE is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. The Investigator assessed whether the AE was possibly or probably related to study drug. In addition, all laboratory-derived hematologic toxicities were assumed to be possibly or probably related to study drug.
    • Number of Participants With the Indicated Serious Adverse Events (SAE) Related to Study Drug [ Time Frame: Par. were evaluated until death/disease progression or 2 years in Study BEX104505. Par. who completed 2 years in BEX104505 were followed in study BEX104528 for up to 125 months. Data are included from both Study BEX104505 and Study BEX104528. ]
      An SAE is any event occurring at any dose that results in any of the following: death, a life-threatening adverse drug experience (ADE; at immediate risk of death from the experience as it occurred), inpatient hospitalization/prolongation of existing hospitalization, a persistent/significant disability/incapacity, or a congenital anomaly/birth defect. Medical events that may not result in death, be life-threatening, or require hospitalization may be considered to be a serious ADEs when based upon appropriate medical judgment. Relatedness was based on the Investigator's medical judgement.
    • Number of Participants With the Indicated Type of Infection [ Time Frame: Par. were evaluated until death/disease progression or 2 years in Study BEX104505. Par. who completed 2 years in BEX104505 were followed in study BEX104528 for up to 125 months. Data are included from both Study BEX104505 and Study BEX104528. ]
      An infection is the colonization of a host organism by a parasite species. Infecting parasites seek to use the host's resources to reproduce, often resulting in disease. Specimen samples of the body fluid are cultured for testing whether the infectious organism is present and grown in the culture media to assess the growth pattern of the organisms present in the specimen. The culture results could be positive or negative. The positive culture results indicate that the tested participant has t

      Original Secondary Outcome: Secondary endpoint analyses are duration of response, time to progression, time-to-treatment failure, safety, and survival. [ Time Frame: Subjects followed for life or 10 years when entered into Study 104528 ]

      Information By: GlaxoSmithKline

      Dates:
      Date Received: July 30, 2009
      Date Started: June 1998
      Date Completion:
      Last Updated: November 30, 2016
      Last Verified: November 2016