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) - Study Results

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

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
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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.

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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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.

[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 ]

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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 ]

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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) ]

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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 ]

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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 ]

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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) ]

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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) ]

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8. Secondary:

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

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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) ]

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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) ]

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11. Secondary:

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

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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) ]

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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 ]

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14. Secondary:

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

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15. Secondary:

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

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16. Secondary:

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

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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
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Results Point of Contact:

Name/Title: GSK Response Center
Organization: GlaxoSmithKline
phone: 866-435-7343

No publications provided

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