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Pivotal Study of Iodine I 131 Tositumomab for Chemotherapy-refractory Low-grade or Transformed Low-grade B-cell Non-Hodgkin's Lymphoma

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT00989664
First received: October 1, 2009
Last updated: March 15, 2012
Last verified: January 2011
History of Changes
Results First Received: March 15, 2012  
Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Condition: Lymphoma, Non-Hodgkin
Intervention: Biological: Tositumomab and Iodine I 131 Tositumomab

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
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Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Participants (par.) received radioimmunotherapy of tositumomab (TST) and Iodine I 131 TST in 2 phases (Ph.): Ph. 1, dosimetric dose; Ph. 2, therapeutic dose. Par. were evaluated until disease progression, they died, or they were on study for 2 years. Par. completing 2 years of study could enter a long-term follow-up study (BEX104526; NCT00240591).

Reporting Groups
  Description
TST and I 131 TST Participants received a dosimetric dose (DD) consisting of 450 milligrams (mg) of tositumomab (TST) intravenously (IV) immediately followed by I 131 TST (35 mg of TST, of which 1-2 mg was labelled with 5 millicurie [mCi] of I 131) IV. The therapeutic dose (TD) consisted of 450 mg of TST IV, immediately followed by a participant-specific dose of I 131 TST (35 mg of TST labelled with I 131 to administer 75 centigray [cGy] or 65 cGy). The TD was administered 7-14 days after the DD. 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 I 131 TST  
STARTED     61  
COMPLETED     0  
NOT COMPLETED     61  
Non-compliant or Uncooperative                 1  
Condition/Illness; Study Drug Unrelated                 2  
Progressive Disease                 49  
Death                 1  
Enrolled into Study BEX104526                 7  
Did Not Receive Study Drug                 1  

Period 2:   Long-Term Follow-Up
    TST and I 131 TST  
STARTED     14 [1]
COMPLETED     11  
NOT COMPLETED     3  
Death                 3  
[1] 14 of the 61 participants withdrawing from Study BEX104504 enrolled in the LTFU study.



  Baseline Characteristics
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Reporting Groups
  Description
TST and I 131 TST Participants received a dosimetric dose (DD) consisting of 450 milligrams (mg) of tositumomab (TST) intravenously (IV) immediately followed by I 131 TST (35 mg of TST, of which 1-2 mg was labelled with 5 millicurie [mCi] of I 131) IV. The therapeutic dose (TD) consisted of 450 mg of TST IV, immediately followed by a participant-specific dose of I 131 TST (35 mg of TST labelled with I 131 to administer 75 centigray [cGy] or 65 cGy). The TD was administered 7-14 days after the DD. 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 I 131 TST  
Number of Participants  
[units: participants]
 		  60  
Age [1]
[units: Years]
Mean ± Standard Deviation 		  59.4  ± 10.5  
Gender [1]
[units: Participants]
 		 
Female     22  
Male     38  
Race/Ethnicity, Customized [2]
[units: participants]
 		 
White     58  
Hispanic     1  
Black     1  
[1] Baseline characteristics are summarized for the Intent-to-Treat (ITT) Exposed Population, comprised of all participants who were enrolled in the study and received at least one dose of study drug.
[2] Baseline characteristics are summarized for the ITT Exposed Population, comprised of all participants who were enrolled in the study and received at least one dose of study drug.



  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Number of Participants (Par.) Receiving TST and I 131 TST With a Response >=30 Days Versus Par. With a Response >=30 Days After Their Last Qualifying Chemotherapy Regimen (LQCR), Masked Independent Randomized Radiology and Oncology Review (MIRROR) Panel   [ Time Frame: Participants were evaluated for up to 99.1 months in Study 104504 or were followed in the long-term follow-up study for up to 141.5 months ]
  Show Outcome Measure 1

2.  Primary:   Duration of Response for Par. Receiving TST and I 131 TST With a Response >=30 Days Versus the Number of Par. With a Response >=30 Days After Their LQCR, as Assessed by the MIRROR Panel   [ Time Frame: Participants were evaluated for up to 99.1 months in Study 104504 or were followed in the long-term follow-up study for up to 141.5 months ]
  Show Outcome Measure 2

3.  Secondary:   Number of Participants With Any Uncofirmed Response (CR, Clinical Complete Response [CCR], or PR), CR, CCR, CR+CCR, and PR), as Assessed by the Investigator   [ Time Frame: Participants were evaluated for up to 99.1 months in Study 104504 or were followed in the long-term follow-up study for up to 141.5 months ]
  Show Outcome Measure 3

4.  Secondary:   Number of Participants With Any Confirmed Response (CR, CCR, or PR), Confirmed CR, Confirmed CCR, Confirmed CR+CCR, and Confirmed PR, as Assessed by Investigator   [ Time Frame: Participants were evaluated for up to 99.1 months in Study 104504 or were followed in the long-term follow-up study for up to 141.5 months ]
  Show Outcome Measure 4

5.  Secondary:   Time to Progression of Disease or Death, as Assessed by the Investigator   [ Time Frame: Participants were evaluated for up to 99.1 months in Study 104504 or were followed in the long-term follow-up study for up to 141.5 months ]
  Show Outcome Measure 5

6.  Secondary:   Time to Treatment Failure, as Assessed by the Investigator   [ Time Frame: Participants were evaluated for up to 99.1 months in Study 104504 or were followed in the long-term follow-up study for up to 141.5 months ]
  Show Outcome Measure 6

7.  Secondary:   Overall Survival   [ Time Frame: Participants were evaluated for up to 99.1 months in Study 104504 or were followed in the long-term follow-up study for up to 141.5 months ]
  Show Outcome Measure 7

8.  Secondary:   Number of Participants With Responses of CR, CCR, CR+CCR, and PR Following TST and I 131 TST and Following the LQCR, as Assessed by the Investigator   [ Time Frame: Participants were evaluated for up to 99.1 months in Study 104504 or were followed in the long-term follow-up study for up to 141.5 months ]
  Show Outcome Measure 8

9.  Secondary:   Number of Participants With the Indicated Adverse Events (AE) Related to Study Drug Experienced by at Least 5% of Participants   [ Time Frame: Participants were evaluated for up to 99.1 months in Study 104504 or were followed in the long-term follow-up study for up to 141.5 months ]
  Show Outcome Measure 9

10.  Secondary:   Number of Participants With the Indicated Grade 3 or Grade 4 AEs Experienced by at Least 5% of Participants   [ Time Frame: Participants were evaluated for up to 99.1 months in Study 104504 or were followed in the long-term follow-up study for up to 141.5 months ]
  Show Outcome Measure 10

11.  Secondary:   Number of Participants With the Indicated Grade 3 or Grade 4 AEs Related to Study Drug and Experienced by at Least 5% of Participants   [ Time Frame: Participants were evaluated for up to 99.1 months in Study 104504 or were followed in the long-term follow-up study for up to 141.5 months ]
  Show Outcome Measure 11

12.  Secondary:   Number of Participants With the Indicated Primary Cause of Death   [ Time Frame: Participants were evaluated for up to 99.1 months in Study 104504 or were followed in the long-term follow-up study for up to 141.5 months ]
  Show Outcome Measure 12

13.  Secondary:   Number of Participants With the Indicated Time to Death From the Last Dose of Study Drug   [ Time Frame: Participants were evaluated for up to 99.1 months in Study 104504 or were followed in the long-term follow-up study for up to 141.5 months ]
  Show Outcome Measure 13

14.  Secondary:   Number of Participants With the Indicated Fatal Serious Adverse Events (SAE) Unrelated to Study Drug   [ Time Frame: Participants were evaluated for up to 99.1 months in Study 104504 or were followed in the long-term follow-up study for up to 141.5 months ]
  Show Outcome Measure 14

15.  Secondary:   Number of Participants With the Indicated Fatal SAEs Related to Study Drug   [ Time Frame: Participants were evaluated for up to 99.1 months in Study 104504 or were followed in the long-term follow-up study for up to 141.5 months ]
  Show Outcome Measure 15

16.  Secondary:   Number of Participants With the Indicated SAEs Related to Study Drug   [ Time Frame: Participants were evaluated for up to 99.1 months in Study 104504 or were followed in the long-term follow-up study for up to 141.5 months ]
  Show Outcome Measure 16

17.  Secondary:   Number of Participants With the Indicated Type of Infection   [ Time Frame: Participants were evaluated for up to 99.1 months in Study 104504 or were followed in the long-term follow-up study for up to 141.5 months ]
  Show Outcome Measure 17

18.  Secondary:   Number of Participants With an Infection for Which Anti-infectives Were Administered   [ Time Frame: Participants were evaluated for up to 99.1 months in Study 104504 or were followed in the long-term follow-up study for up to 141.5 months ]
  Show Outcome Measure 18

19.  Secondary:   Number of Participants Who Were Negative for Human Anti-murine Antibodies (HAMA) at Baseline (Before Receiving the Dosimetric Dose) But Positive or Negative After Receiving the Dosimetric Dose   [ Time Frame: HAMA was measured at baseline; Day5; Weeks 7, 17, 25; and then every 12 months while in study BEX104526. Participants were evaluated for up to 99.1 months in Study 104504 or were followed in the long-term follow-up study for up to 141.5 months ]
  Show Outcome Measure 19

20.  Secondary:   Time to HAMA Positivity From the First Dosimetric Dose   [ Time Frame: HAMA was measured at baseline; Day5; Weeks 7, 17, 25; and then every 12 months while in study BEX104526. Participants were evaluated for up to 99.1 months in Study 104504 or were followed in the long-term follow-up study for up to 141.5 months ]
  Show Outcome Measure 20

21.  Secondary:   Number of Participants With the Indicated Grade 3 or Grade 4 Hematologic Toxicities   [ Time Frame: Participants were evaluated for up to 99.1 months in Study 104504 or were followed in the long-term follow-up study for up to 141.5 months ]
  Show Outcome Measure 21

22.  Secondary:   Number of Participants With Hypothyroidism Prior to Therapy and After the Therapeutic Dose   [ Time Frame: Participants were evaluated for up to 99.1 months in Study 104504 or were followed in the long-term follow-up study for up to 141.5 months ]
  Show Outcome Measure 22


  Serious Adverse Events
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  Other Adverse Events
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  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: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT00989664     History of Changes
Other Study ID Numbers: 104504, RIT-II-004
Study First Received: October 1, 2009
Results First Received: March 15, 2012
Last Updated: March 15, 2012
Health Authority: United States: Food and Drug Administration