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Iodine-131 Anti-B1 Antibody Versus Anti-B1 Antibody in Chemotherapy-Relapsed/Refractory Low-Grade or Transformed Low-Grade Non-Hodgkin's Lymphoma

Phase 2

Lymphoma, Non-Hodgkin | Monoclonal antibody | Oncology |GSK plc|Last Updated: Jan 18, 2017

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Trial Design

RandomizedCONTROLLEDDMC
Total Trials1
Total Enrollment78

FDA Designations

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Clinical trial landscape

Iodine-131 Anti-B1 Antibody Versus Anti-B1 Antibody in Chemotherapy-Relapsed/Refractory Low-Grade or Transformed Low-Grade Non-Hodgkin's Lymphoma · 1 trial · 1 indication

Phase 2 1
NCT01573000A Randomized Study of Iodine-131 Anti-b1 Antibody Versus Anti-b1 Antibody in Chemotherapy-relapsed/Refractory Low-grade or Transformed Low-grade Non-Hodgkin's Lymphoma (NHL)Lymphoma, Non-Hodgkin
COMPLETED78 Analytics
PHASE2COMPLETED
A Randomized Study of Iodine-131 Anti-b1 Antibody Versus Anti-b1 Antibody in Chemotherapy-relapsed/Refractory Low-grade or Transformed Low-grade Non-Hodgkin's Lymphoma (NHL)
Lymphoma, Non-HodgkinUnlock trial analytics

Study Endpoints

Primary Endpoints

Number of Participants (Par.) With Confirmed Response as Assessed by the Investigator
Participants were evaluated for up to two years in Study BEX104515 and for up to 11.9 years in Study BEX104526.

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 measurable lesions; no new lesions).

Number of Participants With Confirmed Response Before and After Crossover From Unlabeled TST to TST and Iodine I 131 TST as Assessed by the Investigator
Participants were evaluated for up to two years in Study BEX104515 and for up to 11.9 years in Study BEX104526.

Participants receiving Unlabeled TST with progressive disease (defined as a \>=25% increase from the nadir value of the sum of the products of the longest perpendicular diameters of all measureable 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.) were assessed separately before and after receiving the crossover treatment of I 131 TST for confirmed response, which included participants with CR, CCR, and PR.

Number of Participants With Confirmed Complete Response (CR) as Assessed by the Investigator
Participants were evaluated for up to two years in Study BEX104515 and for up to 11.9 years in Study BEX104526.

CR is defined as the complete resolution of all disease-related radiological abnormalities and the disappearance of all signs and symptoms related to the disease.

Number of Participants (Par.) With a Confirmed Complete Response as Assessed by the Masked Independent Randomized Radiology and Oncology Review (MIRROR) Panel
The MIRROR panel reviewed responses of participants from 17 July 1998 to 17 January 2001

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 measurable lesions; no new lesions).

Number of Participants With Confirmed Complete Response (CR) Before and After Crossover From Unlabeled TST to TST and Iodine I 131 TST as Assessed by the Investigator
Participants were evaluated for up to two years in Study BEX104515 and for up to 11.9 years in Study BEX104526.

Participants receiving Unlabeled TST with progressive disease were assessed separately before and after receiving the crossover treatment of I 131 TST for CR. CR is defined as the complete resolution of all disease-related radiological abnormalities and the disappearance of all signs and symptoms related to the disease.

Number of Participants With Confirmed Clinical Complete Response (CCR) as Assessed by the Investigator
Participants were evaluated for up to two years in Study BEX104515 and for up to 11.9 years in Study BEX104526.

CCR is defined as the complete resolution of all disease-related symptoms; residual foci, thought to be residual scar tissue, are present. Generally, an unchanging lesion =\<2 cm in diameter by radiographic evaluation or =\<1 cm in diameter by physical examination can be considered scar tissue.

Number of Participants With Confirmed Clinical Complete Response (CCR) Before and After Crossover From Unlabeled TST to TST and Iodine I 131 TST as Assessed by the Investigator
Participants were evaluated for up to two years in Study BEX104515 and for up to 11.9 years in Study BEX104526.

Participants receiving Unlabeled TST with progressive disease were assessed separately before and after receiving the crossover treatment of I 131 TST for CCR. CCR is defined as the complete resolution of all disease-related symptoms; residual foci, thought to be residual scar tissue, are present. Generally, an unchanging lesion =\<2 cm in diameter by radiographic evaluation or =\<1 cm in diameter by physical examination can be considered scar tissue.

Number of Participants With Confirmed Complete Response Plus Clinical Complete Response (CR + CCR) as Assessed by the Investigator
Participants were evaluated for up to two years in Study BEX104515 and for up to 11.9 years in Study BEX104526.

CCR is defined as the complete resolution of all disease-related symptoms; residual foci, thought to be residual scar tissue, are present. Generally, an unchanging lesion =\<2 cm in diameter by radiographic evaluation or =\<1 cm in diameter by physical examination can be considered scar tissue. The extent of disease must be unchanged or decreased upon follow-up evaluations. If the extent of disease was unchanged or if further decreases occurred for 6 months or longer, the participant was reclassified as having a CR.

Number of Participants With Confirmed Complete Response Plus Clinical Complete Response (CR + CCR) Before and After Crossover From Unlabeled TST to TST and Iodine I 131 TST as Assessed by the Investigator
Participants were evaluated for up to two years in Study BEX104515 and for up to 11.9 years in Study BEX104526.

Participants receiving Unlabeled TST with progressive disease were assessed separately before and after receiving the crossover treatment of I 131 TST for CR + CCR.

Number of Participants With Confirmed Partial Response (PR) as Assessed by the Investigator
Participants were evaluated for up to two years in Study BEX104515 and for up to 11.9 years in Study BEX104526.

Confirmed PR is defined as a \>=50% reduction in the sum of the products of the longest perpendicular diameters of all measurable lesions, with no new lesions.

Number of Participants With Confirmed Partial Response (PR) Before and After Crossover From Unlabeled TST to TST and Iodine I 131 TST as Assessed by the Investigator
Participants were evaluated for up to two years in Study BEX104515 and for up to 11.9 years in Study BEX104526.

Participants receiving Unlabeled TST with progressive disease were assessed separately before and after receiving the crossover treatment of I 131 TST confirmed PR. Confirmed PR is defined as a \>=50 percent reduction in the sum of the products of the longest perpendicular diameters of all measurable lesions, with no new lesions.

Secondary Endpoints

Number of Participants (Par.) With a Confirmed Response (CR, CCR, or PR) as Assessed by the MIRROR Panel
The MIRROR panel reviewed responses of participants from 17 July 1998 to 17 January 2001
Duration of Response for All Confirmed Responders, Confirmed Complete Responders, and Confirmed Partial Responders
Participants were evaluated for up to two years in Study BEX104515 and for up to 11.9 years in Study BEX104526.
MIRROR Panel Assessments of Duration of Complete Response (Time From the First Documented Response to the First Documented Progression)
The MIRROR panel reviewed responses of participants from 17 July 1998 to 17 January 2001
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Study Design & Arms

AllocationRANDOMIZED
MaskingNONE
ModelCROSSOVER
PurposeTREATMENT

Treatment Arms

ArmTypeDescription
Open-label, two-arm, Arm A and Arm B CrossoverEXPERIMENTALArm A Dosimetric Dose: 450 mg of TST infused over 70 minutes (inclusive of a 10-minute flush) immediately followed by 5 milliCurie (mCi) (35 mg) of I-131 TST infused over 30 minutes (inclusive of a 10-minute flush).• Therapeutic Dose: Seven to 14 days after the dosimetric dose, 450 mg of TST infused over 70 minutes (inclusive of a 10-minute flush) immediately followed by a subject-specific mCi activity (35 mg) of I-131 TST to deliver the desired total body dose (TBD) infused over 30 minutes (inclusive of a 10-minute flush). The desired TBD was 65 cGy for subjects with a baseline platelet count of 100,001-149,999 cells/mm3 and 75 cGy for subjects with a baseline platelet count ≥150,000 cells/mm3. Obese subjects (subjects weighing more than 137% of their calculated lean body weight) were dosed based upon 137% of their calculated lean body mass
Arm B CrossoverEXPERIMENTALArm B Dosimetric Dose: 450 mg of TST infused over 70 minutes (inclusive of a 10-minute flush) immediately followed by 35 mg of TST infused over 30 minutes (inclusive of a 10-minute flush).Therapeutic Dose: Seven to 14 days after the dosimetric dose, 450 mg of TST infused over 70 minutes (inclusive of a 10-minute flush) immediately followed by 35 mg of TST infused over 30 minutes (inclusive of a 10-minute flush). Subjects randomized to Arm B were allowed to cross-over and receive TST/ I-131 TST once their disease had progressed.

Interventions

NameTypeDescription
Iodine-131 Anti-B1 Antibody Versus Anti-B1 Antibody in Chemotherapy-Relapsed/Refractory Low-Grade or Transformed Low-Grade Non-Hodgkin's Lymphoma (NHL)BIOLOGICALSubjects will be randomized to receive tositumomab and iodine-131 tositumomab (Arm A) or unlabeled tositumomab (Arm B). Subjects randomized to receive unlabeled tositumomab may crossover and receive radiolabeled Iodine-131 tositumomab following progression of their lymphoma. Response in both arms will be assessed at 7 weeks, 13 weeks, and then at 3-monthly intervals for up to 2 years.
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Eligibility Criteria

Age Range18 Years to N/A
SexALL
Healthy VolunteersNo

Inclusion Criteria: * Histologically confirmed low-grade or transformed NHL with evaluable, measurable disease * Tumor had to express CD20 antigen * One to three prior chemotherapy regimens * Karnofsky performance score ≥60% and anticipated survival ≥3 months * Absolute neutrophil count (ANC) \>150...

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