Last updated: 07/17/2024 17:38:51

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

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GSK study ID
393229/005
See study documents
Clinicaltrials.gov ID
NCT00992992
See results summary
EudraCT ID
Not applicable
EU CT Number
Not applicable
Trial status
Study complete
Study complete
Overview
Eligibility
Locations
Study documents
Results summary
Plain language summaries
Additional information

Trial overview

Official title: Phase II Study Of Iodine-131 Anti-B1 Antibody Plus CHOP For Patients With Previously Untreated Mantle Cell Lymphoma
Trial description: 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.
Primary purpose:
Treatment
Trial design:
Single Group Assignment
Masking:
None (Open Label)
Allocation:
Not applicable
Primary outcomes:

Number of participants with the indicated unconfirmed response (complete response, complete response unconfirmed, and partial response)

Timeframe: Every 13 weeks up to 2 years, or every 6 months until disease progression or death (average of 77.8 months)

Secondary outcomes:

Number of participants with the indicated confirmed response (confirmed complete response, complete response unconfirmed, and partial response)

Timeframe: Every 13 weeks up to 2 years, or every 6 months until disease progression or death (average of 77.8 months)

Duration of response for all confirmed responders (CR + CRu + PR)

Timeframe: Every 13 weeks up to 2 years, or every 6 months until disease progression or death (average of 77.8 months)

Duration of response for all unconfirmed responders (CR + CRu + PR)

Timeframe: Every 13 weeks up to 2 years, or every 6 months until disease progression or death (average of 77.8 months)

Duration of response for unconfirmed complete responders

Timeframe: Every 13 weeks up to 2 years, or every 6 months until disease progression or death (average of 77.8 months)

Duration of response for confirmed complete responders

Timeframe: Every 13 weeks up to 2 years, or every 6 months until disease progression or death (average of 77.8 months)

Progression-free survival

Timeframe: 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

Timeframe: Every 13 weeks up to 2 years, or every 6 months until disease progression or death (average of 77.8 months)

Number of participants with any adverse event (AE) or serious adverse event (SAE)

Timeframe: Every 13 weeks up to 2 years, or every 6 months until disease progression or death (average of 77.8 months)

Mean nadir value for absolute neutrophil count (ANC)

Timeframe: Every 13 weeks up to 2 years, or every 6 months until disease progression or death (average of 77.8 months)

Mean nadir value for hemoglobin

Timeframe: Every 13 weeks up to 2 years, or every 6 months until disease progression or death (average of 77.8 months)

Mean nadir values for platelets and white blood cell (WBC) count

Timeframe: Every 13 weeks up to 2 years, or every 6 months until disease progression or death (average of 77.8 months)

Time to nadir for the indicated hematology parameters

Timeframe: Every 13 weeks up to 2 years, or every 6 months until disease progression or death (average of 77.8 months)

Time to recovery from the indicated hematology parameters

Timeframe: Every 13 weeks up to 2 years, or every 6 months until disease progression or death (average of 77.8 months)

Number of participants negative for Human Anti-Murine (mouse) Antibody (HAMA) at Screening who converted to HAMA positivity or remained negative during the course of the study

Timeframe: Screening; at Week 7, Week 13, then every 6 months until disease progression or death (up to 143 months)

Number of participants with an adverse event of cytopenia

Timeframe: Every 13 weeks up to 2 years, or every 6 months until disease progression or death (average of 77.8 months)

Overall Survival

Timeframe: Every 13 weeks up to 2 years, or every 6 months until disease progression or death (average of 77.8 months)

Interventions:
  • Biological/vaccine: Tositumomab and Iodine I 131 Tositumomab followed by CHOP
    • Enrollment:
    25
    Primary completion date:
    2013-30-06
    Observational study model:
    Not applicable
    Time perspective:
    Not applicable
    Clinical publications:
    Andrew Zelenetz, Leslie Popplewell, Ariela Noy, Thierry Horner, Thomas Lin, Vanessa Williams, Gerard Donnelly, George Sgouros, Ivelise Rijo, Chaitanya Divgi. A phase II study of Iodine-131 tositumomab plus chemotherapy in patients with previously untreated mantle cell lymphoma. Clin Lymphoma Myeloma. 2019 DOI: 10.1016/j.clml.2019.04.010
    Medical condition
    Lymphoma, Mantle-Cell
    Product
    tositumomab
    Collaborators
    Not applicable
    Study date(s)
    June 2001 to June 2013
    Type
    Interventional
    Phase
    2

    Participation criteria

    Sex
    Female & Male
    Age
    18+ years
    Accepts healthy volunteers
    No
    • Patients must have a confirmed initial diagnosis of mantle cell non-Hodgkin's lymphoma by histology according to the WHO classification .
    • Patients must have Ann Arbor bulky stage II, stage III, or stage IV disease at diagnosis. Bulky stage II disease is defined as a mediastinal mass greater than one-third of the maximum chest diameter, or any other mass greater than or equal to 10 cm in maximum diameter.
    • Patients who have received prior chemotherapy, biologic therapy, steroids, or radiation therapy as treatment for their MCL
    • Patients with active obstructive hydronephrosis
    Inclusion and exclusion criteria
    Inclusion criteria:
    • Patients must have a confirmed initial diagnosis of mantle cell non-Hodgkin's lymphoma by histology according to the WHO classification .
    • Patients must have Ann Arbor bulky stage II, stage III, or stage IV disease at diagnosis. Bulky stage II disease is defined as a mediastinal mass greater than one-third of the maximum chest diameter, or any other mass greater than or equal to 10 cm in maximum diameter.
    • Patients must have less than an average of 25% of the intratrabecular marrow space involved by NHL in bilateral bone marrow biopsy specimens as assessed microscopically at study entry. A unilateral bone marrow biopsy demonstrating <10% involvement with NHL is also adequate.
    • Patients must have evidence that their tumor tissue expresses the CD20 antigen. Immunoperoxidase stains of paraffin-embedded tissue showing positive reactivity with L26 antibody or immunoperoxidase stains of frozen tissue showing positive reactivity with Anti-B1 Antibody (Coulter Clone) or similar commercially available CD20 antibody or evidence of CD20 positivity by flow cytometry are acceptable evidence of CD20 positivity. This must be performed within 42 days of study entry.
    • Patients must have a performance status of at least 60% on the Karnofsky Performance Scale and an anticipated survival of at least 3 months.
    • Patients must have an ANC greater than or equal to 1500 cells/mm3 and a platelet count greater than or equal to 100,000 cells/mm3 within 14 days of study enrollment. These blood counts must be sustained without support of hematopoietic cytokines or transfusion of blood products.
    • Patients must have adequate renal function (defined as serum creatinine <1.5 times the upper limit of normal) and hepatic function (defined as total bilirubin <1.5 times the upper limit of normal and AST <5 times the upper limit of normal) within 14 days of study enrollment.
    • Patients must have bi-dimensionally measurable disease. At least one lesion must be greater than or equal to 2.0 x 2.0 cm by computerized tomography scan.
    • Females of childbearing potential must have a negative serum pregnancy test within 7 days prior to study enrollment.
    • Patients must have a cardiac left ventricular ejection fraction of greater than or equal to 50% by ventriculography or echocardiogram.
    Exclusion criteria:
    • Patients who have received prior chemotherapy, biologic therapy, steroids, or radiation therapy as treatment for their MCL
    • Patients with active obstructive hydronephrosis
    • Patients with serious illness that would preclude evaluation
    • Patients with prior malignancy other than lymphoma, except for adequately treated skin cancer, in situ cervical cancer, or other cancer for which the patient has been disease free for 5 years
    • Patients with known HIV infection
    • Patients who are HAMA positive
    • Patients with known brain or leptomeningeal metastases.
    • Patients who are pregnant or breastfeeding. Males and females must agree to use a contraceptive method while on study and for 6 months after receiving Iodine-131 Anti-B1 Antibody.
    • Patients with active infection requiring IV anti-infectives at the time of study enrollment.

    Trial location(s)

    This study does not involve prospective enrollment of participants.

    Study documents

    Clinical study report
    Available language(s): English
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    Scientific result summary
    Available language(s): English
    Download document(s)

    If you wish to request for full study report, please contact - [email protected]

    Results overview

    Results posted on ClinicalTrials.gov

    Recruitment status
    Study complete
    Actual primary completion date
    2013-30-06
    Actual study completion date
    2013-30-06

    Plain language summaries

    Plain language summaries of clinical trial results for Phase 2-4 clinical trials that were initiated on or after January 2022 will be posted by GSK within one year following study completion.

    Additional information about the trial

    Additional information
    Not applicable
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