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 9, 2014
Last verified: October 2014

November 4, 2009
October 9, 2014
March 2010
February 2014   (final data collection date for primary outcome measure)
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) ] [ Designated as safety issue: No ]
Progression-free survival is defined as the interval of time from the randomization date until the date of stable disease (SD; failure to attain the criteria needed for a CR or PR and no fulfillment of the criteria for progressive disease [PD]) after two cycles of salvage chemotherapy, progression, or death, whichever occurs first. Disease progression was based on the assessments of independent reviewers for the disease under study. Disease progression was based on imaging data or clinical assessment data (if radiologic assessment data were not possible or assessment was not performed) via the Revised Response Criteria for Malignant Lymphoma (RRCML).
Evaluate the progression-free survival (PFS) in subjects receiving ofatumumab in addition to salvage chemotherapy (O-chemo) compared to subjects receiving rituximab in addition to salvage chemotherapy (R-chemo) [ Time Frame: 2 years ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT01014208 on ClinicalTrials.gov Archive Site
  • 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) ] [ Designated as safety issue: No ]
    OR is defined as the number of participants achieving either a complete response (CR) or a partial response (PR). CR is defined as the complete disappearance of all detectable clinical evidence of disease and disease-related symptoms. PR is defined as at least a 50% decrease from Baseline in the sum of the product of the diameters of target lesions. RRCML was used to assess CR and PR.
  • 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) ] [ Designated as safety issue: No ]
    OR is defined as the number of participants achieving either a complete response (CR) or a partial response (PR). CR is defined as the complete disappearance of all detectable clinical evidence of disease and disease-related symptoms. PR is defined as at least a 50% decrease from Baseline in the sum of the product of the diameters of target lesions. RRCML was used to assess CR and PR.
  • 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) ] [ Designated as safety issue: No ]
    Event-free survival is defined as the time from randomization to progressive disease (PD; disease or physical ailment whose course in most cases is the worsening, growth, or spread of the disease), stable disease (SD; failure to attain the criteria needed for a CR or PR and no fulfillment of the criteria for PD) after completion of 2 cycles of therapy, commencement of a new treatment for diffuse large B cell lymphoma (DLBCL) (e.g., radiotherapy), or death from any cause, whichever occurs first. Disease progression was based on the assessments of independent reviewers for the disease under study. Disease progression was based on imaging data or clinical assessment data (if radiologic assessment data were not possible or assessment was not performed) via the Revised Response Criteria for Malignant Lymphoma (RRCML).
  • Overall Survival (OS) [ Time Frame: From randomization to death due to any cause (assessed for up to 5 years) ] [ Designated as safety issue: No ]
    OS is defined as the time from randomization to death due to any cause. Participants who were still alive by the end of the study were censored.
  • 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) ] [ Designated as safety issue: No ]
    CD34+ cells are a mixture of stem cells and white blood cells of various degrees of maturity. Stem cell mobilization is the process of stimulating the hematopoietic stem cells (CD34+) to move out of the bone marrow and into the bloodstream, where they can be collected via a process called apheresis. Successful mobilization is defined as the collection of >2*10^6 CD34+ cells/kg. Only those participants who commenced mobilization, following the administration of rituximab or ofatumumab in combination with DHAP combination chemotherapy, were assessed. The number of participants with adequate harvest of autologous stem cells (at least 2*10^6 CD34+ cells/kg) after completion of salvage therapy in Cycle 2 and Cycle 3 was analyzed.
  • Number of Participants Completing Autologous Stem Cell Transplant (ASCT) [ Time Frame: Approximately 4 to 6 weeks following Cycle 3 (assessed up to 3 months) ] [ Designated as safety issue: No ]
    The number of participants who completed ASCT is reported.
  • 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]) ] [ Designated as safety issue: No ]
    The FACT-G was developed by the Functional Assessment of Chronic Illness Therapy (FACIT) group for use in adults in a wide range of oncology clinical trial populations. The 27 items of the FACT-G are scored in the following domains: Physical Well-being (7 items), Social/Family Wellbeing (7 items), Emotional Well-being (6 items), and Functional Well-being (7 items). Participants responded to the items on a five-point Likert scale ranging from 0, "Not at all" to 4, "Very much." The total score ranges from 0 to 108; higher scores indicate a better patient-reported outcome/quality of life. Participants were asked to think back over the past week when responding to the items.
  • 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]) ] [ Designated as safety issue: No ]
    The FACT-Lym TOI is a measure that combines the FACT-Lym subscale (15 items; responses to each item range from 0, "Not at all" to 4, "Very much") with two domains taken from the FACT-G (responses to each item range from "Not at all " to "Very much"): Physical Well-being (7 items: lack of energy, nausea, meeting family needs, pain, side effects, feels ill, spends time in bed) and Functional Well-being (7 items: ability to work, work fulfilment, ability to enjoy life, illness acceptance, ability to sleep well, enjoying things done for fun, satisfaction with quality of life). This index is designed to be sensitive to changes in treatment regimens. The total FACT-Lym TOI score ranges from 0 to 116; higher scores indicate a better patient-reported outcome/quality of life. Participants were asked to think back over the past week when responding to the items.
  • 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) ] [ Designated as safety issue: No ]
    Neutrophil (absolute neutrophil count [ANC]) recovery is defined as ANC >=0.5*10^9/Liter and increasing, and platelet (PLT) recovery is defined as PLT >=10*10^9/Liter and increasing. For each cycle, time to ANC recovery is defined as the time from the first dose to the first ANC >=0.5*10^9/Liter and increasing after reaching the lowest value in the cycle. For each cycle, time to PLT recovery is defined as the time from the first dose to the first PLT >=10*10^9/L and increasing after the nadir in the cycle.
  • 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) ] [ Designated as safety issue: No ]
    Engraftment is defined as the time at which both neutrophil engraftment and platelet engraftment has been achieved, and the engraftment date is defined as the later of the neutrophil engraftment date and the platelet engraftment date. If engraftment was not achieved by Day 42 or the last observation, engraftment was deemed to be a failure, and censoring took place at Day 42 or at the last observation.
  • Overall response rate after completion of salvage chemotherapy [ Time Frame: 9 weeks ] [ Designated as safety issue: No ]
  • Ability to mobilize greater than or equal to 2X10^6 CD34+ cells/kg from peripheral blood. [ Time Frame: 9 weeks ] [ Designated as safety issue: No ]
  • Safety, tolerability and health related quality of life measures [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Progression free survival in DHAP subgroup [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Overall survival [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Overall response rate 3 months after ASCT [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • Event-free survival [ Time Frame: 2 years ] [ Designated as safety issue: No ]
Not Provided
Not Provided
 
Ofatumumab Versus Rituximab Salvage Chemoimmunotherapy Followed by Autologous Stem Cell Transplant in Relapsed or Refractory Diffuse Large B Cell Lymphoma
Ofatumumab Versus Rituximab Salvage Chemoimmunotherapy Followed by Autologous Stem Cell Transplant (ASCT) in Relapsed or Refractory Diffuse Large B Cell Lymphoma (DLBCL)

This study is being conducted to compare the efficacy and safety of ofatumumab in addition to salvage chemotherapy versus rituximab in addition to salvage chemotherapy in CD20 positive DLBCL subjects relapsing, or with persistent disease, after first-line treatment with rituximab combined with an anthracycline-based chemotherapy regimen and be eligible for ASCT.

As rituximab-based regimens have become standard first-line treatment in CD20 positive DLBCL, the efficacy of rituximab combined with salvage chemotherapy in the second-line setting has decreased and there is a need for new therapies in patients progressing or relapsing after first-line rituximab-based therapy. Replacement of rituximab with ofatumumab in the second-line setting, following progression/relapse after first-line rituximab-containing regimens, offers the potential to overcome relative or complete rituximab resistance and thus improve response rates, the ability to proceed to consolidative HDT/ASCT, and overall survival.

Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Lymphoma, Large-Cell, Diffuse
  • Drug: OFATUMUMAB + DHAP
    3 cycles of treatment will be administered. Each cycle will last 21 days. ofatumumab dose: cycle 1, day 1 - 1000 mg; cycle 1, day 8 - 1000 mg; cycle 2, day 1 and cycle 3, day 1 - 1000 mg. DHAP regimen: dexamethasone - 40 mg on days 1, 2, 3, and 4 of dosing cycle; cisplatin - 100 mg/m2/24hrs continuous on day 1 of dosing cycle; cytarabine - 2g/m2 q12 hrs (2 doses) on day 2 of dosing cycle.
  • Drug: RITUXIMAB + DHAP
    3 cycles of treatment will be administered. Each cycle will last 21 days. rituximab dose: cycle 1, day 1 - 375 mg/m2; cycle 1, day 8 - 375 mg/m2; cycle 2, day 1 and cycle 3, day 1 - 375 mg/m2. DHAP regimen: dexamethasone - 40 mg on days 1, 2, 3, and 4 of dosing cycle; cisplatin - 100 mg/m2/24hrs continuous on day 1 of dosing cycle; cytarabine - 2g/m2 q12 hrs (2 doses) on day 2 of dosing cycle.
  • Experimental: OFATUMUMAB + DHAP CHEMOTHERAPY REGIMEN
    This study is a parallel arm study, with ofatumumab + DHAP. The Investigators are required to prospectively choose to treat all of their subjects with either DHAP chemotherapy regimens in combination with ofatumumab. All subjects will receive the same ofatumumab regimen and dose.
    Intervention: Drug: OFATUMUMAB + DHAP
  • Active Comparator: RITUXIMAB + DHAP CHEMOTHERAPY REGIMEN
    This study is a parallel arm study, with rituximab + DHAP. The Investigators are required to prospectively choose to treat all of their subjects with either DHAP chemotherapy regimens in combination with rituximab. All subjects will receive the same rituximab regimen and dose.
    Intervention: Drug: RITUXIMAB + DHAP
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
447
November 2018
February 2014   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Subjects with CD20 positive DLBCL or grade 3b follicular lymphoma (FL) at original diagnosis.
  • Refractory to, or relapsed following, first-line treatment with rituximab combined with anthracycline- or anthracenedione-based chemotherapy as defined by the protocol.
  • CT with involvement of 2 or more clearly demarcated lesions/ nodes with a long axis > 1.5 cm and short axis >= 1.0cm or 1 clearly demarcated lesion/ node with a long axis > 2.0 cm and short axis >= 1.0 cm.
  • Baseline FDG-PET scans must demonstrate positive lesions compatible with CT defined anatomical tumor sites.
  • Age 18 yrs or older.
  • ECOG performance status of 0, 1 or 2.
  • Eligible for high dose chemotherapy and ASCT.
  • Resolution of toxicities from first-line therapy to a grade that in the opinion of the investigator does not contraindicate study participation.
  • Signed written informed consent.

Exclusion Criteria:

  • Previous cancer therapy for lymphoma, with the exception of first-line rituximab/ anthracycline- or anthracenedione-based chemotherapy, monotherapy rituximab prior to or combined with first-line chemotherapy, as maintenance therapy, and radiotherapy in a limited field or as a part of the first-line treatment plan.
  • Any anti-cancer therapy, except limited field radiotherapy, within 2 weeks prior to start of study therapy.
  • Planned post-randomization chronic glucocorticoid use (limited acute use is allowed and defined by the protocol) unless administered as therapy for mild COPD or asthma.
  • Clinically significant cardiac disease, active or chronic infections, serious significant diseases, other cancer within last 5 years. History of significant cerebrovascular disease.
  • Prior treatment with anti-CD20 monoclonal antibodies with the exception of rituximab.
  • Abnormal/ inadequate WBC count, liver, and kidney function.
  • Pregnant or lactating women or female patients of child-bearing potential (or male patients with such partners) not willing to use adequate contraception during and up to 1 year following dosing completion.
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
Ireland,   United States,   Argentina,   Austria,   Belgium,   China,   Czech Republic,   Denmark,   Estonia,   Finland,   Germany,   Greece,   Hungary,   India,   United Kingdom,   Israel,   Japan,   Korea, Republic of,   Netherlands,   Norway,   Poland,   Russian Federation,   Singapore,   Spain,   Sweden,   Thailand
 
NCT01014208
110928
Yes
GlaxoSmithKline
GlaxoSmithKline
Not Provided
Study Director: GSK Clinical Trials GlaxoSmithKline
GlaxoSmithKline
October 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP