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Study of Radiolabeled Monoclonal Antibody Anti-B1 for the Treatment of B-Cell Lymphomas and Extended Study to Determine the Safety and Efficacy of Coulter Clone® 131Iodine-B1 Radioimmunotherapy of Advanced Non-Hodgkin's Lymphoma

This study has been completed.
Sponsor:
Information provided by:
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT01536561
First received: January 26, 2012
Last updated: March 1, 2012
Last verified: February 2012
History of Changes
Results First Received: February 23, 2012  
Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Single Group Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Condition: Lymphoma, Non-Hodgkin
Intervention: Biological: Radiolabeled Monoclonal Antibody Anti-B1 for the Treatment of B-Cell Lymphomas (Tositumomab and Iodine I 131 Tositumomab)

  Participant Flow
  Hide Participant Flow

Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
After an initial treatment (IT), 14 participants (14 of the 59 particpants receiving the IT) who achieved a partial or complete response and subsequently developed progressive disease were retreated (administered at either the initial dose or a reduced dose if a >=Grade toxicity had occurred after the IT) at the time of disease progression.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Participants received radioimmunotherapy of tositumomab (TST) and Iodine I 131 TST in 2 phases: Phase 1, dosimetric dose; Phase 2, therapeutic dose. After radioimmunotherapy, participants could have entered a 10-year Long-Term Follow-Up study (Study BEX104526; NCT00240591) for continued evaluation.

Reporting Groups
  Description
TST and Iodine I 131 TST Participants received 1 to 3 dosimetric doses (DD) consisting of 0, 95, or 475 milligrams (mg) of tositumomab (TST) intravenously (IV) followed by 5.0 millicurie (mCi) of Iodine (I 131) TST IV. This was followed by a therapeutic dose (TD) administered 7-14 days after the DD, starting at a total body dose (TBD) of 25 centiGray (cGy) or 65 cGy (only for participants who had undergone bone marrow transplantation) with increments of 10 cGy at each dose level (DL) until the maximum tolerated dose (MTD) was achieved. Participants were re-dosed with a second TD when their tumor stopped regressing (was no longer shrinking). Participants who had completed at least 2 years of follow-up after administration of TST/I 131 TST during the TD phase and had signed the informed consent to participate in the Long-Term Follow-Up (LTFU) study (BEX104526) were followed for up to 10 years. Participants did not receive any study medication during the LTFU study.

Participant Flow for 2 periods

 Period 1:   Dosimetric and Therapeutic Treatment
    TST and Iodine I 131 TST  
STARTED     59  
COMPLETED     0  
NOT COMPLETED     59  
Progressive Disease                 40  
Received Alternate Treatment                 2  
Adverse Event                 1  
Lost to Follow-up                 1  
Death                 2  
Enrolled in Study BEX104526                 13  

Period 2:   Long-Term Follow-Up
    TST and Iodine I 131 TST  
STARTED     13  
COMPLETED     13  
NOT COMPLETED     0  



  Baseline Characteristics
  Hide Baseline Characteristics

Reporting Groups
  Description
TST and Iodine I 131 TST Participants received 1 to 3 dosimetric doses (DD) consisting of 0, 95, or 475 milligrams (mg) of tositumomab (TST) intravenously (IV) followed by 5.0 millicurie (mCi) of Iodine (I 131) TST IV. This was followed by a therapeutic dose (TD) administered 7-14 days after the DD, starting at a total body dose (TBD) of 25 centiGray (cGy) or 65 cGy (only for participants who had undergone bone marrow transplantation) with increments of 10 cGy at each dose level (DL) until the maximum tolerated dose (MTD) was achieved. Participants were re-dosed with a second TD when their tumor stopped regressing (was no longer shrinking). Participants who had completed at least 2 years of follow-up after administration of TST/I 131 TST during the TD phase and had signed the informed consent to participate in the Long-Term Follow-Up (LTFU) study (BEX104526) were followed for up to 10 years. Participants did not receive any study medication during the LTFU study.

Baseline Measures
    TST and Iodine I 131 TST  
Number of Participants  
[units: participants]
 		  59  
Age  
[units: Years]
Mean ± Standard Deviation 		  49.9  ± 12.6  
Gender  
[units: Participants]
 		 
Female     22  
Male     37  
Race/Ethnicity, Customized  
[units: participants]
 		 
White     54  
Hispanic     2  
Black     3  



  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Number of Participants (Par.) During Initial Treatment Exposed to the Indicated Dose Levels of the Therapeutic Dose (TD), Re-dose, and Total Dose (TD + Re-dose)   [ Time Frame: Participants who completed at least 2 years of follow-up in Study BEX104728 were invited to enroll in BEX104526 for long-term follow-up. Participants were evaluated in Study BEX104728 and Study BEX104526 for up to 15.6 years. ]
  Show Outcome Measure 1

2.  Primary:   Number of Participants During Retreatment Exposed to the Indicated Dose Levels of the TD, Re-dose, and Total Dose (TD + Re-dose)   [ Time Frame: Participants who completed at least 2 years of follow-up in Study BEX104728 were invited to enroll in BEX104526 for long-term follow-up. Participants were evaluated in Study BEX104728 and Study BEX104526 for up to 15.6 years. ]
  Show Outcome Measure 2

3.  Primary:   Maximum Tolerated Dose (MTD) of TST/I 131 TST Evaluated in the Study   [ Time Frame: Participants who completed at least 2 years of follow-up in Study BEX104728 were invited to enroll in BEX104526 for long-term follow-up. Participants were evaluated in Study BEX104728 and Study BEX104526 for up to 15.6 years. ]
  Show Outcome Measure 3

4.  Primary:   Tumor/Organ Dosimetry of TST/I 131 TST for All Predoses (Initial Treatment)   [ Time Frame: Serial anterior and posterior gamma whole body scans were obtained 1 hour after the administration of the dosimetric dose (on Day 0), and then daily for at least 5 days until Day 7 ]
  Show Outcome Measure 4

5.  Secondary:   Tumor/Organ Dosimetry at the Indicated Predoses of 475 mg, 95 mg, and 0 mg (Initial Treatment)   [ Time Frame: Serial anterior and posterior gamma whole body scans were obtained 1 hour after the administration of the dosimetric dose (on Day 0), and then daily for at least 5 days until Day 7 ]
  Show Outcome Measure 5

6.  Secondary:   Number of Participants (Par.) With the Indicated Response as Assessed by the Investigator   [ Time Frame: Participants who completed at least 2 years of follow-up in Study BEX104728 were invited to enroll in BEX104526 for long-term follow-up. Participants were evaluated in Study BEX104728 and Study BEX104526 for up to 15.6 years. ]
  Show Outcome Measure 6

7.  Secondary:   Number of Participants (Par.) With Confirmed Response as Assessed by the Investigator   [ Time Frame: Participants who completed at least 2 years of follow-up in Study BEX104728 were invited to enroll in BEX104526 for long-term follow-up. Participants were evaluated in Study BEX104728 and Study BEX104526 for up to 15.6 years. ]
  Show Outcome Measure 7

8.  Secondary:   Duration of Response for All Unconfirmed Responders (CR, CCR, or PR) as Assessed by the Investigator   [ Time Frame: Participants who completed at least 2 years of follow-up in Study BEX104728 were invited to enroll in BEX104526 for long-term follow-up. Participants were evaluated in Study BEX104728 and Study BEX104526 for up to 15.6 years. ]
  Show Outcome Measure 8

9.  Secondary:   Time to Progression of Disease or Death   [ Time Frame: Participants who completed at least 2 years of follow-up in Study BEX104728 were invited to enroll in BEX104526 for long-term follow-up. Participants were evaluated in Study BEX104728 and Study BEX104526 for up to 15.6 years. ]
  Show Outcome Measure 9

10.  Secondary:   Overall Survival   [ Time Frame: Participants who completed at least 2 years of follow-up in Study BEX104728 were invited to enroll in BEX104526 for long-term follow-up. Participants were evaluated in Study BEX104728 and Study BEX104526 for up to 15.6 years. ]
  Show Outcome Measure 10

11.  Secondary:   Half-life: Initial Half-life (t1/2 Alpha) and Terminal Half-life (t1/2 Beta) of I 131 TST for the Antibody Predose Levels of 0 mg, 95 mg, and 475 mg   [ Time Frame: Blood samples were collected at the end of the infusion (Study Day 0) and at 0.5, 1, 2, 4, 12, 24, 36, 48, 72, 96, and 120 hours following the end of the infusion. ]
  Show Outcome Measure 11

12.  Secondary:   Clearance (CL) of I 131 TST for the Indicated Antibody Predose Levels   [ Time Frame: Blood samples were collected at the end of the infusion (Study Day 0) and at 0.5, 1, 2, 4, 12, 24, 36, 48, 72, 96, and 120 hours following the end of the infusion. ]
  Show Outcome Measure 12

13.  Secondary:   Area Under the Concentration Time Curve (AUC) of I 131 TST for the Indicated Antibody Predose Levels   [ Time Frame: Blood samples were collected at the end of the infusion (Study Day 0) and at 0.5, 1, 2, 4, 12, 24, 36, 48, 72, 96, and 120 hours following the end of the infusion. ]
  Show Outcome Measure 13

14.  Secondary:   Maximum Blood Concentration (Cmax) of I 131 TST for the Indicated Antibody Predose Levels   [ Time Frame: Blood samples were collected at the end of the infusion (Study Day 0) and at 0.5, 1, 2, 4, 12, 24, 36, 48, 72, 96, and 120 hours following the end of the infusion ]
  Show Outcome Measure 14

15.  Secondary:   Volume of Distribution at Steady State (Vss) of I 131 TST for the Indicated Antibody Predose Levels   [ Time Frame: Blood samples were collected at the end of the infusion (Study Day 0) and at 0.5, 1, 2, 4, 12, 24, 36, 48, 72, 96, and 120 hours following the end of the infusion ]
  Show Outcome Measure 15

16.  Secondary:   Number of Participants Who Developed Human Anti-mouse Antibodies (HAMA Postivitiy) After Receiving Tositumomab   [ Time Frame: Participants who completed at least 2 years of follow-up in Study BEX104728 were invited to enroll in BEX104526 for long-term follow-up. Participants were evaluated in Study BEX104728 and Study BEX104526 for up to 15.6 years. ]
  Show Outcome Measure 16

17.  Secondary:   Time to HAMA Positivity From the First Dosimetric Dose (Time From Baseline [Dosimetric Dose] to the First Reported Presence of HAMA)   [ Time Frame: Participants who completed at least 2 years of follow-up in Study BEX104728 were invited to enroll in BEX104526 for long-term follow-up. Participants were evaluated in Study BEX104728 and Study BEX104526 for up to 15.6 years. ]
  Show Outcome Measure 17

18.  Secondary:   Number of Participants With the Indicated Type of Infection   [ Time Frame: Participants who completed at least 2 years of follow-up in Study BEX104728 were invited to enroll in BEX104526 for long-term follow-up. Participants were evaluated in Study BEX104728 and Study BEX104526 for up to 15.6 years. ]
  Show Outcome Measure 18

19.  Secondary:   Time to Nadir for the Indicated Hematologic Laboratory Parameters   [ Time Frame: Participants who completed at least 2 years of follow-up in Study BEX104728 were invited to enroll in BEX104526 for long-term follow-up. Participants were evaluated in Study BEX104728 and Study BEX104526 for up to 15.6 years. ]
  Show Outcome Measure 19

20.  Secondary:   Time to Recovery to Baseline for the Indicated Hematologic Laboratory Parameters   [ Time Frame: Participants who completed at least 2 years of follow-up in Study BEX104728 were invited to enroll in BEX104526 for long-term follow-up. Participants were evaluated in Study BEX104728 and Study BEX104526 for up to 15.6 years. ]
  Hide Outcome Measure 20

Measure Type Secondary
Measure Title Time to Recovery to Baseline for the Indicated Hematologic Laboratory Parameters
Measure Description Time to recovery to baseline is the time required for recovery from nadir values to baseline values.
Time Frame Participants who completed at least 2 years of follow-up in Study BEX104728 were invited to enroll in BEX104526 for long-term follow-up. Participants were evaluated in Study BEX104728 and Study BEX104526 for up to 15.6 years.  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
ITT Exposed Population. Only those participants for which nadir could be calculated were analyzed. Some participants did not have post-baseline data available.

Reporting Groups
  Description
TST and Iodine I 131 TST: Initial Treatment Participants received 1 to 3 dosimetric doses (DD) consisting of 0, 95, or 475 milligrams (mg) of tositumomab (TST) intravenously (IV) followed by 5.0 millicurie (mCi) of Iodine (I 131) TST IV. This was followed by a therapeutic dose (TD) administered 7-14 days after the DD, starting at a total body dose (TBD) of 25 centiGray (cGy) or 65 cGy (only for participants who had undergone bone marrow transplantation) with increments of 10 cGy at each dose level (DL) until the maximum tolerated dose (MTD) was achieved. Participants were re-dosed with a second TD when their tumor stopped regressing (was no longer shrinking). Participants who had completed at least 2 years of follow-up after administration of TST/I 131 TST during the TD phase and had signed the informed consent to participate in the Long-Term Follow-Up (LTFU) study (BEX104526) were followed for up to 10 years. Participants did not receive any study medication during the LTFU study.
TST and Iodine I 131 TST: Retreatment After the "Initial Treatment" (DD of TST and Iodine I 131 TST, followed by TD), participants who achieved a partial response (PR:>=50% reduction in the sum of the products of the longest perpendicular diameters of all measurable lesions; no new lesions) or complete response (CR: complete resolution of all disease-related radiological abnormalities and the disappearance of all signs and symptoms related to the disease) and subsequently developed progressive disease were retreated at the time of disease progression. Retreatment was administered either at the initial TD of TST/I 131 TST or at a reduced dose if a Grade 2 or greater toxicity had occurred after the "Initial Treatment." Participants who had completed at least 2 years of follow-up after administration of TST/I 131 TST during the TD phase and had signed the informed consent to participate in the LTFU study (BEX104526) were followed for up to 10 years. Participants did not receive any study medication during the LTFU stu

Measured Values
    TST and Iodine I 131 TST: Initial Treatment     TST and Iodine I 131 TST: Retreatment  
Number of Participants Analyzed  
[units: participants]
 		  46     4  
Time to Recovery to Baseline for the Indicated Hematologic Laboratory Parameters  
[units: days]
Median ( 95% Confidence Interval ) 		   
Time to recovery to baseline, ANC, n=23, 2     79.0  
  ( 57.0 to 108.0 )   		  74.0  
  ( 44.0 to 74.0 )  
Time to recovery to baseline, hemoglobin, n=46, 4     42.0  
  ( 34.0 to 55.0 )   		  38.5  
  ( 6.0 to NA ) [1]
Time to recovery to baseline, platelets, n=45, 4     57.0  
  ( 48.0 to 76.0 )   		  39.0  
  ( 26.0 to 39.0 )  
Time to recovery to baseline, WBC count, n=46, 3     69.0  
  ( 49.0 to 91.0 )   		  77.0  
  ( 56.0 to 77.0 )  
[1] The SAS procedure was not able to calculate the upper limit of the confidence interval.

No statistical analysis provided for Time to Recovery to Baseline for the Indicated Hematologic Laboratory Parameters



21.  Secondary:   Nadir Values for the Hematologic Parameters ANC, Platelets, and WBC Count   [ Time Frame: Participants who completed at least 2 years of follow-up in Study BEX104728 were invited to enroll in BEX104526 for long-term follow-up. Participants were evaluated in Study BEX104728 and Study BEX104526 for up to 15.6 years. ]
  Show Outcome Measure 21

22.  Secondary:   Nadir Values for Hemoglobin, a Hematologic Parameter   [ Time Frame: Participants who completed at least 2 years of follow-up in Study BEX104728 were invited to enroll in BEX104526 for long-term follow-up. Participants were evaluated in Study BEX104728 and Study BEX104526 for up to 15.6 years. ]
  Show Outcome Measure 22


  Serious Adverse Events
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  Other Adverse Events
  Show Other Adverse Events


  More Information
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Limitations and Caveats
Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.  


Results Point of Contact:  
Name/Title: GSK Response Center
Organization: GlaxoSmithKline
phone: 866-435-7343


Publications:


Responsible Party: Cheri Hudson; Clinical Disclosure Advisor, GSK Clinical Disclosure
ClinicalTrials.gov Identifier: NCT01536561     History of Changes
Other Study ID Numbers: 104728
Study First Received: January 26, 2012
Results First Received: February 23, 2012
Last Updated: March 1, 2012
Health Authority: United States: Food and Drug Administration