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Ofatumumab Versus Rituximab Salvage Chemoimmunotherapy Followed by Autologous Stem Cell Transplant in Relapsed or Refractory Diffuse Large B Cell Lymphoma (ORCHARRD)

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT01014208
First received: November 4, 2009
Last updated: October 30, 2014
Last verified: October 2014
Results First Received: October 9, 2014  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Condition: Lymphoma, Large-Cell, Diffuse
Interventions: Drug: OFATUMUMAB + DHAP
Drug: RITUXIMAB + 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
Participants who were refractory to, or had relapsed following, first-line treatment with rituximab in combination with an anthracycline- or anthracenedione-containing chemotherapy regimen, and who were eligible for autologous stem cell transplant (ASCT), were eligible for enrollment.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Eligible participants were randomized to receive either rituximab or ofatumumab in addition to salvage chemotherapy.

Reporting Groups
  Description
Rituximab + Chemotherapy Participants received 3 cycles (21 days per cycle) of rituximab combined with salvage chemotherapy (SC): either the DHAP regimen (3 cycles of dexamethasone, cytarabine, cisplatin [DHAP]) or the DVD regimen (DHAP-VIM [etoposide, ifosfamide, mesna, methotrexate]-DHAP). Rituximab (375 milligrams per meters squared [mg/m^2]) was infused intravenously (IV) on Day (D) 1 (or up to 3 days prior to D1) and D8 (+/-2 days) of Cycle 1 of the SC, and then on D1 only of Cycles 2 and 3. The DHAP regimen (SC) contained: dexamethasone (40 mg/day) administered orally or IV on Days 1, 2, 3, or 4 of each cycle; cisplatin (100 mg/m^2/day) as an IV continuous infusion on D1 of each cycle; and cytarabine 2 grams (g)/m^2 over 3 hours every 12 hours (2 doses) for each infusion on D2 of each cycle. VIM: etoposide (90 mg/m^2 IV on Days 1, 3, and 5), ifosfamide (1200 mg/m^2 IV on Days 1, 2, 3, 4, and 5), mesna (10 or 20 mg/kilogram [kg] IV on Days 1, 2, 3, 4, and 5), methotrexate (30 mg/m^2 IV on Days 1 and 5).
Ofatumumab + Chemotherapy Participants received 3 cycles (21 days per cycle) of ofatumumab combined with SC: either the DHAP regimen (three cycles of DHAP) or the DVD regimen (DHAP-VIM-DHAP). Ofatumumab (1000 mg/1000 milliliter [mL]) was infused IV on Day 1 (or up to 3 days prior to Day 1) and Day 8 (+/-2 days) of Cycle 1 of the SC, and then on Day 1 only of Cycles 2 and 3. The DHAP regimen (SC) contained: dexamethasone (40 mg/day) administered orally or IV on Days 1, 2, 3, or 4 of each cycle; cisplatin (100 mg/[m^2]/day) as an IV continuous infusion on Day 1 of each cycle; and cytarabine 2 g/m^2 over 3 hours every 12 hours (2 doses) for each infusion on Day 2 of each cycle. VIM: etoposide (90 mg/m^2 IV on Days 1, 3, and 5), ifosfamide (1200 mg/m^2 IV on Days 1, 2, 3, 4, and 5), mesna (10 or 20 mg/kg IV on Days 1, 2, 3, 4, and 5), methotrexate (30 mg/m^2 IV on Days 1 and 5).

Participant Flow:   Overall Study
    Rituximab + Chemotherapy     Ofatumumab + Chemotherapy  
STARTED     225     222  
Intent-to-Treat Population     223     222  
Ongoing     97     101  
COMPLETED     0     0  
NOT COMPLETED     225     222  
Lost to Follow-up                 2                 8  
Physician Decision                 1                 0  
Participant Withdrew Consent                 10                 11  
Death                 113                 102  
Ongoing                 97                 101  
Did Not Receive Study Drug                 2                 0  



  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.
No text entered.

Reporting Groups
  Description
Rituximab + Chemotherapy Participants received 3 cycles (21 days per cycle) of rituximab combined with salvage chemotherapy (SC): either the DHAP regimen (3 cycles of dexamethasone, cytarabine, cisplatin [DHAP]) or the DVD regimen (DHAP-VIM [etoposide, ifosfamide, mesna, methotrexate]-DHAP). Rituximab (375 milligrams per meters squared [mg/m^2]) was infused intravenously (IV) on Day (D) 1 (or up to 3 days prior to D1) and D8 (+/-2 days) of Cycle 1 of the SC, and then on D1 only of Cycles 2 and 3. The DHAP regimen (SC) contained: dexamethasone (40 mg/day) administered orally or IV on Days 1, 2, 3, or 4 of each cycle; cisplatin (100 mg/m^2/day) as an IV continuous infusion on D1 of each cycle; and cytarabine 2 grams (g)/m^2 over 3 hours every 12 hours (2 doses) for each infusion on D2 of each cycle. VIM: etoposide (90 mg/m^2 IV on Days 1, 3, and 5), ifosfamide (1200 mg/m^2 IV on Days 1, 2, 3, 4, and 5), mesna (10 or 20 mg/kilogram [kg] IV on Days 1, 2, 3, 4, and 5), methotrexate (30 mg/m^2 IV on Days 1 and 5).
Ofatumumab + Chemotherapy Participants received 3 cycles (21 days per cycle) of ofatumumab combined with SC: either the DHAP regimen (three cycles of DHAP) or the DVD regimen (DHAP-VIM-DHAP). Ofatumumab (1000 mg/1000 milliliter [mL]) was infused IV on Day 1 (or up to 3 days prior to Day 1) and Day 8 (+/-2 days) of Cycle 1 of the SC, and then on Day 1 only of Cycles 2 and 3. The DHAP regimen (SC) contained: dexamethasone (40 mg/day) administered orally or IV on Days 1, 2, 3, or 4 of each cycle; cisplatin (100 mg/[m^2]/day) as an IV continuous infusion on Day 1 of each cycle; and cytarabine 2 g/m^2 over 3 hours every 12 hours (2 doses) for each infusion on Day 2 of each cycle. VIM: etoposide (90 mg/m^2 IV on Days 1, 3, and 5), ifosfamide (1200 mg/m^2 IV on Days 1, 2, 3, 4, and 5), mesna (10 or 20 mg/kg IV on Days 1, 2, 3, 4, and 5), methotrexate (30 mg/m^2 IV on Days 1 and 5).
Total Total of all reporting groups

Baseline Measures
    Rituximab + Chemotherapy     Ofatumumab + Chemotherapy     Total  
Number of Participants  
[units: participants]
  223     222     445  
Age  
[units: Years]
Mean ± Standard Deviation
  53.4  ± 12.22     55.2  ± 10.80     54.3  ± 11.55  
Gender  
[units: Participants]
     
Female     88     85     173  
Male     135     137     272  
Race/Ethnicity, Customized  
[units: Participants]
     
African American/African Heritage     4     4     8  
American Indian or Alaska Native     0     1     1  
Asian - Central/South Asian Heritage     3     4     7  
Asian - East Asian Heritage     24     31     55  
Asian - Japanese Heritage     19     22     41  
Asian - South East Asian Heritage     4     4     8  
Asian - Mixed Race     0     1     1  
White - Arabic/North African Heritage     1     1     2  
White - White/Caucasian/European Heritage     168     151     319  
Missing     0     3     3  
Number of participants with the indicated SaaIPI scores [1]
[units: Participants]
     
0 or 1     136     133     269  
2 or 3     87     89     176  
Number of participants in the indicated categories per best response to first-line treatment [2]
[units: Participants]
     
Late relapsers     66     63     129  
Early relapsers/Refractory     157     159     316  
[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 a SaaIPI score reflecting low, intermediate, and high risk of disease.
[2] Late relapsers are those participants with a complete response (CR: complete disappearance of all detectable clinical evidence of disease/disease-related symptoms) >12 months after first-line treatment. Early relapsers/refractory are those participants with a CR <= 12 months, PR (>=50% decrease from Baseline in the sum of the product of the diameters of target lesions), SD (failure to attain CR or PR; no fulfillment of PD), or PD (disease/physical ailment that has worsened/grown/spread) after first-line treatment.



  Outcome Measures
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1.  Primary:   Progression-free Survival as Assessed by Independent Reviewers   [ Time Frame: From randomization until the date of stable disease after two cycles of salvage chemotherapy, progression, or death (assessed for up to 5 years) ]

2.  Secondary:   Number of Participants With Overall Response (OR) and Complete Response (CR) After Salvage Chemoimmunotherapy   [ Time Frame: At completion of up to 3 cycles of salvage chemoimmunotherapy (assessed up to 9 weeks) ]

3.  Secondary:   Number of Participants With Overall Response (OR) and Complete Response (CR) Three Months After Autologous Stem Cell Transplant   [ Time Frame: At 3 months after completion of autologous stem cell transplantation (ASCT) (assessed up to 6 months) ]

4.  Secondary:   Event-free Survival   [ Time Frame: From randomization to progressive disease, stable disease after completion of 2 cycles of therapy, commencement of a new treatment for DLBCL, or death due to any cause (assessed for up to 5 years) ]

5.  Secondary:   Overall Survival (OS)   [ Time Frame: From randomization to death due to any cause (assessed for up to 5 years) ]

6.  Secondary:   Number of Participants With the Ability to Mobilize at Least 2 Million Cluster of Differentiation (CD)34+ Cells Per Kilogram From Peripheral Blood   [ Time Frame: During Cycles 2 and/or 3 (Weeks 4-9) ]

7.  Secondary:   Number of Participants Completing Autologous Stem Cell Transplant (ASCT)   [ Time Frame: Approximately 4 to 6 weeks following Cycle 3 (assessed up to 3 months) ]

8.  Secondary:   Change From Baseline in Functional Assessment of Cancer Therapy-General (FACT-G) During Treatment   [ Time Frame: Baseline and the end of the treatment period (until approximately 4 to 6 weeks following Cycle 3 [assessed up to 3 months]) ]

9.  Secondary:   Change From Baseline in the Functional Assessment of Cancer Therapy Lymphoma Trial Outcome Index (FACT-Lym TOI) Total Score During Treatment   [ Time Frame: Baseline and the end of the treatment period (until approximately 4 to 6 weeks following Cycle 3 [assessed up to 3 months]) ]

10.  Secondary:   Time to Neutrophil and Platelet Recovery After Each Cycle of Salvage Chemotherapy   [ Time Frame: From the start of each cycle for a maximum of 5 weeks per cycle (assessed during treatment period of Baseline up to approximately 3 months) ]

11.  Secondary:   Time to Engraftment After High-dose Therapy (HDT)/ASCT   [ Time Frame: From ASCT up to 42 days post-ASCT (Baseline up to approximately 4.5 months) ]


  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


Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT01014208     History of Changes
Other Study ID Numbers: 110928
Study First Received: November 4, 2009
Results First Received: October 9, 2014
Last Updated: October 30, 2014
Health Authority: United States: Institutional Review Board
United States: Food and Drug Administration