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Phase II Study of Ofatumumab Plus Ifosfamide, Carboplatin, Etoposide (ICE) or Dexamethasone, Cytarabine, Cisplatin (DHAP) Chemotherapy Regimen in Relapsed/ Refractory Diffuse Large B Cell Lymphoma (DLBCL)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT00823719
First received: January 8, 2009
Last updated: March 7, 2013
Last verified: February 2013
Results First Received: June 21, 2012  
Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Single Group Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Condition: Lymphoma, Large-Cell, Diffuse
Interventions: Drug: ofatumumab + ICE
Drug: ofatumumab + DHAP

  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
No text entered.

Reporting Groups
  Description
Ofatumumab + DHAP Participants received 3 cycles (21 days per each cycle) of ofatumumab combined with salvage chemotherapy. Ofatumumab (1000 milligrams [mg]) was intravenously (IV) infused on Day 1 (or up to 3 days prior to Day 1) and Day 8 (+/-2 days) of Cycle 1 of the salvage chemotherapy, and then on Day 1 only of Cycles 2 and 3. The DHAP (dexamethasone, cytarabine, cisplatin) regimen (salvage chemotherapy) contained: dexamethasone (40 mg/day) administered orally or IV on Days 1, 2, 3, or 4 of each cycle; cisplatin (100 mg/square meter [m^2]/day) as an IV continuous infusion on Day 1 of each cycle; and cytarabine 2 gram (g)/m^2 over 3 hours (hr) every 12 hr (2 doses) for each infusion on Day 2 of each cycle.
Ofatumumab + ICE Participants received 3 cycles (21 days per each cycle) of ofatumumab combined with salvage chemotherapy. Ofatumumab (1000 mg) was IV infused on Day 1 (or up to 3 days prior to Day 1) and Day 8 (+/-2 days) of Cycle 1 of the salvage chemotherapy, and then on Day 1 only of Cycles 2 and 3. The ICE (ifosfamide, carboplatin, etoposide) regimen (salvage chemotherapy) contained: etoposide (100 mg/m^2/day) administered IV on Days 1, 2, and 3 of each cycle; carboplatin (up to 800 mg) on Day 2 of each cycle; and ifosfamide plus mesna, both at 5 g/m^2/day as an IV continuous infusion on Day 2 of each cycle.

Participant Flow:   Overall Study
    Ofatumumab + DHAP     Ofatumumab + ICE  
STARTED     26     35  
COMPLETED     20     24  
NOT COMPLETED     6     11  
Adverse Event                 1                 2  
Physician Decision                 1                 4  
Withdrawal by Subject                 0                 1  
Disease Progression                 4                 4  



  Baseline Characteristics
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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.
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Reporting Groups
  Description
Ofatumumab + DHAP Participants received 3 cycles (21 days per each cycle) of ofatumumab combined with salvage chemotherapy. Ofatumumab (1000 milligrams [mg]) was intravenously (IV) infused on Day 1 (or up to 3 days prior to Day 1) and Day 8 (+/-2 days) of Cycle 1 of the salvage chemotherapy, and then on Day 1 only of Cycles 2 and 3. The DHAP (dexamethasone, cytarabine, cisplatin) regimen (salvage chemotherapy) contained: dexamethasone (40 mg/day) administered orally or IV on Days 1, 2, 3, or 4 of each cycle; cisplatin (100 mg/square meter [m^2]/day) as an IV continuous infusion on Day 1 of each cycle; and cytarabine 2 gram (g)/m^2 over 3 hours (hr) every 12 hr (2 doses) for each infusion on Day 2 of each cycle.
Ofatumumab + ICE Participants received 3 cycles (21 days per each cycle) of ofatumumab combined with salvage chemotherapy. Ofatumumab (1000 mg) was IV infused on Day 1 (or up to 3 days prior to Day 1) and Day 8 (+/-2 days) of Cycle 1 of the salvage chemotherapy, and then on Day 1 only of Cycles 2 and 3. The ICE (ifosfamide, carboplatin, etoposide) regimen (salvage chemotherapy) contained: etoposide (100 mg/m^2/day) administered IV on Days 1, 2, and 3 of each cycle; carboplatin (up to 800 mg) on Day 2 of each cycle; and ifosfamide plus mesna, both at 5 g/m^2/day as an IV continuous infusion on Day 2 of each cycle.
Total Total of all reporting groups

Baseline Measures
    Ofatumumab + DHAP     Ofatumumab + ICE     Total  
Number of Participants  
[units: participants]
  26     35     61  
Age  
[units: Years]
Mean ± Standard Deviation
  49.7  ± 13.79     53.0  ± 13.02     51.6  ± 13.34  
Gender  
[units: Participants]
     
Female     11     15     26  
Male     15     20     35  
Race/Ethnicity, Customized  
[units: participants]
     
African American/African Heritage     2     2     4  
Asian-Central/South Asian Heritage     1     0     1  
Asian-Japanese/East or South East Asian Heritage     1     0     1  
White     22     33     55  
Number of participants with the indicated number of risk factors [1]
[units: participants]
     
0 or 1     13     19     32  
2 or 3     13     16     29  
Number of participants in the indicated categories per best response to first line treatment [2]
[units: participants]
     
Late relapsers     4     8     12  
Early relapsers/Refractory     22     27     49  
[1] The secondary age adjusted international prognostic index (SaaIPI) is assessed according to the absence or presence of 3 risk factors (RFs) at the start of Screening: Eastern Cooperative Oncology Group performance status greater than 1, lactate dehydrogenase level greater than the upper level of normal, and Ann Arbor stage II or IV disease. The presence of 0, 1, and 2/ 3 RFs corresponds to an SaaIPI score reflecting low, intermediate, and high risk of disease.
[2] Late relapsers are those participants with a complete response (CR) >12 months after adequate R-CHOP-like first-line treatment. Early relapsers are those participants with a CR <= 12 months and >=28 days prior to study treatment after adequate first-line treatment. Refractory participants are those with a CR <28 days, partial response, stable disease, or progressive disease following first-line treatment.



  Outcome Measures
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1.  Primary:   Number of Participants With Overall Response (OR), as Assessed by the Investigator   [ Time Frame: From Day 14 (Study Day 56) to Day 21 (approximately Study Day 63) of treatment Cycle 3, or earlier in the case of early withdrawal or missing response assessment for Cycle 3 ]

2.  Secondary:   Number of Participants With CR, as Assessed by the Investigator   [ Time Frame: From Day 14 (Study Day 56) to Day 21 (approximately Study Day 63) of treatment Cycle 3, or earlier in the case of early withdrawal or missing response assessment for Cycle 3 ]

3.  Secondary:   Number of Participants With the Ability to Mobilize at Least 2 Million Cluster of Differentiation (CD)34+ Cells Per Kilogram (kg) From Peripheral Blood   [ Time Frame: During treatment Cycle 2 (Study Days 22-42) and/or Cycle 3 (Study Days 43-63) ]

4.  Secondary:   Progression-free Survival (PFS)   [ Time Frame: From Day 14 (Study Day 56) to Day 21 (approximately Study Day 63) of treatment Cycle 3, or earlier in the case of early withdrawal or missing response assessment for Cycle 3 ]

5.  Secondary:   Overall Survival   [ Time Frame: From Day 14 (Study Day 56) to Day 21 (approximately Study Day 63) of treatment Cycle 3, or earlier in the case of early withdrawal or missing response assessment for Cycle 3 ]

6.  Secondary:   Area Under the Concentration-time Curve From Time Zero to Infinity, AUC(0-inf), of Ofatumumab at the First Infusion (Cycle 1, Day 1) and the Last Infusion (Cycle 3)   [ Time Frame: Cycle 1 Day 1 (Study Day 1; up to 1 week) and Cycle 3 (Study Day 43; up to 6 weeks) ]

7.  Secondary:   Area Under the Concentration-time Curve During the Dosing Interval (AUC(0-tau)) of Ofatumumab at the Last Infusion (Cycle 3)   [ Time Frame: Cycle 3 (Study Day 43; 3 weeks) ]

8.  Secondary:   Clearance (CL) of Ofatumumab   [ Time Frame: Study Day 1 up to Study Day 85 (up to 12 weeks) ]

9.  Secondary:   Maximum Plasma Concentration (Cmax) of Ofatumumab at the First Infusion (Cycle 1 Day 1), Second Infusion (Cycle 1 Day 8), and Last Infusion (Cycle 3)   [ Time Frame: Cycle 1 Day 1 (Study Day 1; up to 48 hours), Cycle 1 Day 8 (Study Day 8; up to 24 hours), Cycle 3 (Study Day 43; up to 48 hours) ]

10.  Secondary:   Trough Plasma Concentration (Ctrough) of Ofatumumab Prior to Second Infusion (Cycle 1 Day 8), Third Infusion (Cycle 2), and Last Infusion (Cycle 3)   [ Time Frame: Cycle 1 Day 8 (Study Day 8; up to 8 hours prior to infusion start), Cycle 2 (Study Day 22; up to 7 hours prior to infusion start), Cycle 3 (Study Day 43; up to 6 hours prior to infusion start) ]

11.  Secondary:   Terminal Phase Half-life (t1/2) of Ofatumumab   [ Time Frame: Study Day 1 up to Study Day 85 (up to 12 weeks) ]

12.  Secondary:   Volume of Distribution at Steady State (Vss) of Ofatumumab   [ Time Frame: Study Day 1 up to Study Day 85 (up to 12 weeks) ]

13.  Secondary:   Number of Participants Who Were Positive and Negative for Human Anti-human Antibodies (HAHA) at the Indicated Time Points   [ Time Frame: Study Day 1 up to approximately Study Day 63 ]

14.  Secondary:   Number of Participants With the Indicated Adverse Events (AEs) Associated With Neutropenia   [ Time Frame: Study Day 1 to approximately Study Day 63 ]

15.  Secondary:   Number of Participants With the Indicated AEs Associated With Decreased Hemoglobin Counts   [ Time Frame: Study Day 1 to approximately Study Day 63 ]

16.  Secondary:   Number of Participants With the Indicated AEs Associated With Decreased Platelet Counts   [ Time Frame: Study Day 1 to approximately Study Day 63 ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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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
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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.


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


No publications provided by GlaxoSmithKline

Publications automatically indexed to this study:

Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT00823719     History of Changes
Other Study ID Numbers: 110927
Study First Received: January 8, 2009
Results First Received: June 21, 2012
Last Updated: March 7, 2013
Health Authority: United States: Institutional Review Board
United States: Food and Drug Administration