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)

This study has been completed.

Sponsor:

Information provided by (Responsible Party):

GlaxoSmithKline

ClinicalTrials.gov Identifier:

NCT01573000

First received: March 8, 2012

Last updated: September 6, 2012

Last verified: April 2012

History of Changes

Results First Received: April 12, 2012

Study Type:	Interventional
Study Design:	Allocation: Randomized; Endpoint Classification: Safety/Efficacy Study; Intervention Model: Crossover Assignment; Masking: Open Label; Primary Purpose: Treatment
Condition:	Lymphoma, Non-Hodgkin
Intervention:	Biological: Iodine-131 Anti-B1 Antibody Versus Anti-B1 Antibody in Chemotherapy-Relapsed/Refractory Low-Grade or Transformed Low-Grade Non-Hodgkin's Lymphoma (NHL)

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)/Iodine I 131 TST (Arm A) or unlabeled TST (Arm B) in 2 phases: dosimetric and therapeutic dose. Arm B par. were allowed to crossover and receive I 131 TST, if disease progressed. After TST treatment, par. could have entered a Long-Term Follow-Up study (BEX104526; NCT00240591).

Reporting Groups

Description

TST and Iodine I 131 TST

Participants received a dosimetric dose (DD) consisting of 450 milligrams (mg) of tositumomab (TST) intravenously (IV) followed by 5.0 millicurie (mCi) of Iodine I 131 and 35 mg of TST IV. The therapeutic dose (TD) consisting of 450 mg of TST IV, followed by a participant-specific dose of I 131 (75 centigray [cGy] or 65 cGy) and 35 mg of TST IV, 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.

Unlabeled TST

Participants received a DD consisting of 450 mg and 35 mg of unlabelled TST IV. The TD consisting of 450 mg and 35 mg of TST IV was administered 7-14 days after the DD. Participants randomized to receive 450 mg and 35 mg of unlabelled TST IV during the DD and TD phase were allowed to crossover and receive I 131 TST using the same regimen used in the TST and Iodine I 131 TST treatment arm once their disease had progressed as long as they still fulfilled the protocol entry criteria. Participants who had completed at least 2 years of follow-up after administration of 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 study.

Participant Flow for 3 periods

Period 1: Dosimetric and Therapeutic Treatment

	TST and Iodine I 131 TST	Unlabeled TST
STARTED	42	36
COMPLETED	7 ^[1]	1 ^[1]
NOT COMPLETED	35	35
Lack of Efficacy	27	32
Lost to Follow-up	4	2
Death	0	1
Withdrawal by Subject	2	0
Received Other Treatment	2	0

[1]	These participants completed 2 years of follow up and enrolled in BEX104526.

Period 2: Crossover Phase

	TST and Iodine I 131 TST	Unlabeled TST
STARTED	0	19 ^[1]
COMPLETED	0	1 ^[2]
NOT COMPLETED	0	18
Lack of Efficacy	0	13
Lost to Follow-up	0	2
Death	0	3

[1]	19 of 36 par. randomized to receive Unlabeled TST crossed over to receive TST and Iodine I 131 TST.
[2]	This participant completed 2 years of follow up and enrolled in BEX104526.

Period 3: Long-Term Follow-Up

	TST and Iodine I 131 TST	Unlabeled TST
STARTED	14 ^[1]	5 ^[2]
COMPLETED	11	4 ^[3]
NOT COMPLETED	3	1
Death	3	0
Lost to Follow-up	0	1

[1]	14 of the 35 participants withdrawing from Study BEX104515 enrolled in long-term follow-up study.
[2]	5 of the 35 participants withdrawing from Study BEX104515 enrolled in long-term follow-up study.
[3]	One participant who received crossover treatment was lost to follow up.

Baseline Characteristics

Hide Baseline Characteristics

Reporting Groups

	Description
TST and Iodine I 131 TST	Participants received a dosimetric dose (DD) consisting of 450 milligrams (mg) of tositumomab (TST) intravenously (IV) followed by 5.0 millicurie (mCi) of Iodine I 131 and 35 mg of TST IV. The therapeutic dose (TD) consisting of 450 mg of TST IV, followed by a participant-specific dose of I 131 (75 centigray [cGy] or 65 cGy) and 35 mg of TST IV, 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.
Unlabeled TST	Participants received a DD consisting of 450 mg and 35 mg of unlabelled TST IV. The TD consisting of 450 mg and 35 mg of TST IV was administered 7-14 days after the DD. Participants randomized to receive 450 mg and 35 mg of unlabelled TST IV during the DD and TD phase were allowed to crossover and receive I 131 TST using the same regimen used in the TST and Iodine I 131 TST treatment arm once their disease had progressed as long as they still fulfilled the protocol entry criteria. Participants who had completed at least 2 years of follow-up after administration of 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 study.
Total	Total of all reporting groups

Baseline Measures

	TST and Iodine I 131 TST	Unlabeled TST	Total
Number of Participants [units: participants]	42	36	78
Age [units: Years] Mean ± Standard Deviation	56.3 ± 11.6	55.4 ± 12.8	55.8 ± 12.1
Gender, Customized [units: Participants]
Female	19	18	37
Male	23	18	41
Race/Ethnicity, Customized [units: participants]
White	39	33	72
Hispanic	1	1	2
Asian	0	1	1
Black	1	1	2
Other/Unknown	1	0	1

Outcome Measures

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1. Primary:

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

Show Outcome Measure 1

2. Primary:

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 [ Time Frame: Participants were evaluated for up to two years in Study BEX104515 and for up to 11.9 years in Study BEX104526. ]

Show Outcome Measure 2

3. Primary:

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

Show Outcome Measure 3

4. Primary:

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

Show Outcome Measure 4

5. Primary:

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 [ Time Frame: Participants were evaluated for up to two years in Study BEX104515 and for up to 11.9 years in Study BEX104526. ]

Show Outcome Measure 5

6. Primary:

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

Show Outcome Measure 6

7. Primary:

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 [ Time Frame: Participants were evaluated for up to two years in Study BEX104515 and for up to 11.9 years in Study BEX104526. ]

Show Outcome Measure 7

8. Primary:

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

Show Outcome Measure 8

9. Primary:

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 [ Time Frame: Participants were evaluated for up to two years in Study BEX104515 and for up to 11.9 years in Study BEX104526. ]

Show Outcome Measure 9

10. Primary:

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

Show Outcome Measure 10

11. Primary:

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 [ Time Frame: Participants were evaluated for up to two years in Study BEX104515 and for up to 11.9 years in Study BEX104526. ]

Show Outcome Measure 11

12. Secondary:

Number of Participants (Par.) With a Confirmed Response (CR, CCR, or PR) as Assessed by the MIRROR Panel [ Time Frame: The MIRROR panel reviewed responses of participants from 17 July 1998 to 17 January 2001 ]

Show Outcome Measure 12

13. Secondary:

Duration of Response for All Confirmed Responders, Confirmed Complete Responders, and Confirmed Partial Responders [ Time Frame: Participants were evaluated for up to two years in Study BEX104515 and for up to 11.9 years in Study BEX104526. ]

Show Outcome Measure 13

14. Secondary:

MIRROR Panel Assessments of Duration of Complete Response (Time From the First Documented Response to the First Documented Progression) [ Time Frame: The MIRROR panel reviewed responses of participants from 17 July 1998 to 17 January 2001 ]

Show Outcome Measure 14

15. Secondary:

MIRROR Panel Assessments of Duration of Confirmed Response (Time From the First Documented Response to the First Documented Progression) [ Time Frame: The MIRROR panel reviewed responses of participants from 17 July 1998 to 17 January 2001 ]

Show Outcome Measure 15

16. Secondary:

Time to Progression of Disease or Death as Assessed by the Investigator [ Time Frame: Participants were evaluated for up to two years in Study BEX104515 and for up to 11.9 years in Study BEX104526. ]

Show Outcome Measure 16

17. Secondary:

Time to Progression of Disease or Death in Participants Before and After Crossover From Unlabeled TST to TST and Iodine I 131 TST as Assessed by the Investigator [ Time Frame: Participants were evaluated for up to two years in Study BEX104515 and for up to 11.9 years in Study BEX104526. ]

Show Outcome Measure 17

18. Secondary:

MIRROR Panel Assessed Time to Response (Time From the Date of Enrollment to the First Documented Response (PR, CR, CCR) [ Time Frame: The MIRROR panel reviewed responses of participants from 17 July 1998 to 17 January 2001 ]

Show Outcome Measure 18

19. Secondary:

MIRROR Panel Assessed Progression-free Survival [ Time Frame: The MIRROR panel reviewed responses of participants from 17 July 1998 to 17 January 2001 ]

Show Outcome Measure 19

20. Secondary:

Overall Survival [ Time Frame: Participants were evaluated for up to two years in Study BEX104515 and for up to 11.9 years in Study BEX104526. ]

Show Outcome Measure 20

21. Secondary:

Number of Participants With the Indicated Drug-Related (DR) Adverse Events (AEs) Experienced by 3 or More Participants [ Time Frame: Participants were evaluated for up to two years in Study BEX104515 and for up to 11.9 years in Study BEX104526. ]

Show Outcome Measure 21

22. Secondary:

Number of Participants With the Indicated Type of Infection [ Time Frame: Participants were evaluated for up to two years in Study BEX104515 and for up to 11.9 years in Study BEX104526. ]

Show Outcome Measure 22

23. Secondary:

Number of Participants With an Infection for Which Anti-infectives Were Administered [ Time Frame: Participants were evaluated for up to two years in Study BEX104515 and for up to 11.9 years in Study BEX104526. ]

Show Outcome Measure 23

24. Secondary:

Number of Participants With the Indicated Grade 3 or Grade 4 AEs Experienced by 3 or More Participants [ Time Frame: Participants were evaluated for up to two years in Study BEX104515 and for up to 11.9 years in Study BEX104526. ]

Show Outcome Measure 24

25. Secondary:

Number of Participants With the Indicated Grade 3 or Grade 4 Drug-related AEs Experienced by 3 or More Participants [ Time Frame: Participants were evaluated for up to two years in Study BEX104515 and for up to 11.9 years in Study BEX104526. ]

Show Outcome Measure 25

26. Secondary:

Number of Participants With the Indicated Primary Cause of Death [ Time Frame: Participants were evaluated for up to two years in Study BEX104515 and for up to 11.9 years in Study BEX104526. ]

Show Outcome Measure 26

27. Secondary:

Number of Participants With a Time to Death From the Last Dose of Study Drug Less Than or Equal to 30 Days or More Than 30 Days [ Time Frame: Participants were evaluated for up to two years in Study BEX104515 and for up to 11.9 years in Study BEX104526. ]

Show Outcome Measure 27

28. Secondary:

Number of Participants With the Indicated Serious Adverse Events (SAE) Related to Study Drug [ Time Frame: Participants were evaluated for up to two years in Study BEX104515 and for up to 11.9 years in Study BEX104526. ]

Show Outcome Measure 28

29. Secondary:

Number of Participants With the Indicated Fatal SAEs Related to Study Drug [ Time Frame: Participants were evaluated for up to two years in Study BEX104515 and for up to 11.9 years in Study BEX104526. ]

Show Outcome Measure 29

30. Secondary:

Time to Nadir and Time to Recovery to Baseline in Hematologic Laboratory Evaluations [ Time Frame: Participants were evaluated for up to two years in Study BEX104515 and for up to 11.9 years in Study BEX104526. ]

Show Outcome Measure 30

31. Secondary:

Nadir Values for ANC, a Hematologic Parameter [ Time Frame: Participants were evaluated for up to two years in Study BEX104515 and for up to 11.9 years in Study BEX104526. ]

Show Outcome Measure 31

32. Secondary:

Nadir Values for Hemoglobin, a Hematologic Parameter [ Time Frame: Participants were evaluated for up to two years in Study BEX104515 and for up to 11.9 years in Study BEX104526. ]

Show Outcome Measure 32

33. Secondary:

Nadir Values for the Hematologic Parameters Platelets and WBC Count [ Time Frame: Participants were evaluated for up to two years in Study BEX104515 and for up to 11.9 years in Study BEX104526. ]

Show Outcome Measure 33

34. Secondary:

Number of Participants With the Indicated Grade 3 or Grade 4 Hematologic Toxicities [ Time Frame: Participants were evaluated for up to two years in Study BEX104515 and for up to 11.9 years in Study BEX104526. ]

Show Outcome Measure 34

35. Secondary:

Duration of the Indicated Grade 3 or Grade 4 Hematologic Toxicities [ Time Frame: Participants were evaluated for up to two years in Study BEX104515 and for up to 11.9 years in Study BEX104526. ]

Show Outcome Measure 35

36. Secondary:

Time to Human Anti-Murine Antibodies (HAMA) Positivity From the First Dosimetric Dose [ Time Frame: Participants were evaluated for up to two years in Study BEX104515 and for up to 11.9 years in Study BEX104526. ]

Show Outcome Measure 36

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:

	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.
	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.
	Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed. Restriction Description: GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.

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 of Results:

Fowler JF. Correction to Kasibhatla et al. How much radiation is the chemotherapy worth in advanced head and neck cancer? (Int j radiat oncol biol phys 2007;68:1491-1495). Int J Radiat Oncol Biol Phys. 2008 Jun 1;71(2):326-9.

Responsible Party:	GlaxoSmithKline
ClinicalTrials.gov Identifier:	NCT01573000 History of Changes
Other Study ID Numbers:	104515
Study First Received:	March 8, 2012
Results First Received:	April 12, 2012
Last Updated:	September 6, 2012
Health Authority:	United States: Food and Drug Administration

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