Clinical Trial: Safety and Efficacy Study of Iodine-131 Anti-B1 Antibody Plus CHOP For Untreated Mantle Cell Lymphoma

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

Official Title: Phase II Study Of Iodine-131 Anti-B1 Antibody Plus CHOP For Patients With Previously Untreated Mantle Cell Lymphoma

Brief Summary: The primary efficacy endpoint of this study is to determine the duration of response of the sequential administration of Iodine-131 Anti-B1 Antibody followed by six cycles of CHOP for patients with previously untreated Mantle Cell Lymphoma (MCL). The secondary efficacy endpoints for this study are to determine the response rate, confirmed response rate, complete response rate, confirmed complete response rate, duration of response for confirmed responders, duration of response for complete responders, duration of response for confirmed complete responders, progression-free survival, time to treatment failure, and the predictive value of detection of minimal residual disease by molecular techniques on response duration. The pharmacokinetic endpoint is to determine the total body residence time of Iodine-131 Anti-B1 Antibody following the dosimetric dose. The safety endpoints are to determine the incidence of adverse experiences, hematologic toxicity, (e.g., nadir, time to nadir, and time to recovery), use of supportive care, percent of patients converting to human anti-murine antibody (HAMA) positivity, the effects of Iodine-131 Anti-B1 Antibody on the growth and function of hematopoietic progenitor cells, and survival of patients with previously untreated MCL treated with Iodine-131 Anti-B1 Antibody followed by six cycles of CHOP.

Detailed Summary:
Sponsor: GlaxoSmithKline

Current Primary Outcome: Number of Participants With the Indicated Unconfirmed Response (Complete Response, Complete Response Unconfirmed, and Partial Response) [ Time Frame: Every 13 weeks up to 2 years, or every 6 months until disease progression or death (average of 77.8 months) ]

Participants with response include those with complete response (CR: complete disappearance of all detectable clinical and radiographic evidence of disease and the disappearance of all disease-related symptoms), complete response unconfirmed (CRu: CR, with one of the following: residual lymph node mass >1.5 centimeters [cm] that has regressed by more than 75% in the sum of the product of the diameters or indeterminate bone marrow), or partial response (PR: >=50% reduction in the sum of the products of the longest perpendicular diameters of all measurable lesions; no new lesions).


Original Primary Outcome: To determine the response rate of sequential administration of Iodine I 131 Tositumomab followed by six cycles of CHOP chemotherapy for patients with previously untreated MCL. [ Time Frame: Patients will be evaluate under long-term follow-up every six months until death. ]

Current Secondary Outcome:

  • Number of Participants With the Indicated Confirmed Response (Confirmed Complete Response, Complete Response Unconfirmed, and Partial Response) [ Time Frame: Every 13 weeks up to 2 years, or every 6 months until disease progression or death (average of 77.8 months) ]
    A confirmed response is defined as a response that was confirmed by two separate response evaluations occurring at least 4 weeks apart. Participants with a confirmed response include those with complete response (CR: complete disappearance of all detectable clinical and radiographic evidence of disease and the disappearance of all disease-related symptoms), complete response unconfirmed (CRu: CR, with one of the following: residual lymph node mass >1.5 cm that has regressed by more than 75% in the sum of the product of the diameters or indeterminate bone marrow), or partial response (PR: >=50% reduction in the sum of the products of the longest perpendicular diameters of all measurable lesions; no new lesions). The individual rows for confirmed CR, confirmed CRu, and confirmed PR represent confirmation of the same response. For example, a confirmed CR indicates that a CR was followed by another CR at least 4 weeks later.
  • Duration of Response for All Confirmed Responders (CR + CRu + PR) [ Time Frame: Every 13 weeks up to 2 years, or every 6 months until disease progression or death (average of 77.8 months) ]
    Complete response (CR) is defined as the complete disappearance of all detectable clinical and radiographic evidence of disease and the disappearance of all disease-related symptoms. Complete response unconfirmed (CRu) is defined as CR, with one of the following: residual lymph node mass >1.5 cm that has regressed by more than 75% in the sum of the product of the diameters or indeterminate bone marrow. Partial response (PR) is defined as a >=50% reduction in the sum of the products of the longest perpendicular diameters of all measurable lesions; no new lesions. For participants with CR, CRu, or PR, duration of response is defined as the time from the first documented response to the first documented progression.
  • Duration of Response for All Unconfirmed Responders (CR + CRu + PR) [ Time Frame: Every 13 weeks up to 2 years, or every 6 months until disease progression or death (average of 77.8 months) ]
    Complete response (CR) is defined as the complete disappearance of all detectable clinical and radiographic evidence of disease and the disappearance of all disease-related symptoms. Complete response unconfirmed is defined as CR, with one of the following: residual lymph node mass >1.5 cm that has regressed by more than 75% in the sum of the product of the diameters or indeterminate bone marrow. Partial response (PR) is defind as a >=50% reduction in the sum of the products of the longest perpendicular diameters of all measurable lesions; no new lesions. Duration of response is defined as the time from the first documented response to the first documented progression.
  • Duration of Response for Unconfirmed Complete Responders [ Time Frame: Every 13 weeks up to 2 years, or every 6 months until disease progression or death (average of 77.8 months) ]
    Complete response is defined as the complete disappearance of all detectable clinical and radiographic evidence of disease and the disappearance of all disease-related symptoms. Duration of response is defined as the time from the first documented response to the first documented progression.
  • Duration of Response for Confirmed Complete Responders [ Time Frame: Every 13 weeks up to 2 years, or every 6 months until disease progression or death (average of 77.8 months) ]
    Complete response is the complete disappearance of all detectable clinical and radiographic evidence of disease and the disappearance of all disease-related symptoms. A confirmed response is defined as a response that was confirmed by two separate response evaluations occurring at least 4 weeks apart. Duration of response is defined as the time from the first documented response to the first documented progression.
  • Progression-free Survival [ Time Frame: Every 13 weeks up to 2 years, or every 6 months until disease progression or death (average of 77.8 months) ]
    Progression-free survival is defined as the time from the start of treatment (i.e., the dosimetric dose) to the first documented 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. Individual lesions must have been greater than 2 centimeters (cm) in diameter by radiographic evaluation or greater than 1 cm in diameter by physical examination.
  • Time to Treatment Failure [ Time Frame: Every 13 weeks up to 2 years, or every 6 months until disease progression or death (average of 77.8 months) ]
    Time to treatment failure is defined as the time from the date of the dosimetric dose to the first occurrence of treatment withdrawal, decision to seek additional therapy, study removal, disease progression, alternative therapy, or death.
  • Number of Participants With Any Adverse Event (AE) or Se

    Original Secondary Outcome: To assess the efficacy by molecular techniques on response duration, pharmacokinetics, and safety of the sequential administration of iodine I 131 tositumomab followed by six cycles of CHOP for patients with previously untreated MCL. [ Time Frame: Patients will be evaluate under long-term follow-up every six months until death. ]

    Information By: GlaxoSmithKline

    Dates:
    Date Received: October 8, 2009
    Date Started: June 2001
    Date Completion:
    Last Updated: February 27, 2014
    Last Verified: November 2013