Ofatumumab Versus Rituximab Salvage Chemoimmunotherapy Followed by Autologous Stem Cell Transplant in Relapsed or Refractory Diffuse Large B Cell Lymphoma (ORCHARRD)
This study is currently recruiting participants.
Verified May 2013 by GlaxoSmithKline
Sponsor:
GlaxoSmithKline
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT01014208
First received: November 4, 2009
Last updated: May 16, 2013
Last verified: May 2013
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Purpose
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.
| Condition | Intervention | Phase |
|---|---|---|
|
Lymphoma, Large-Cell, Diffuse |
Drug: OFATUMUMAB + DHAP Drug: RITUXIMAB + DHAP |
Phase 3 |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment |
| Official Title: | Ofatumumab Versus Rituximab Salvage Chemoimmunotherapy Followed by Autologous Stem Cell Transplant (ASCT) in Relapsed or Refractory Diffuse Large B Cell Lymphoma (DLBCL) |
Resource links provided by NLM:
Further study details as provided by GlaxoSmithKline:
Primary Outcome Measures:
- 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 ]
Secondary Outcome Measures:
- Overall and complete 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 ]
- Overall survival [ Time Frame: 2 years ] [ Designated as safety issue: No ]
- Overall and complete 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 ]
| Estimated Enrollment: | 410 |
| Study Start Date: | March 2010 |
| Estimated Study Completion Date: | November 2018 |
| Estimated Primary Completion Date: | March 2014 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
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.
|
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.
|
|
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.
|
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.
|
Detailed Description:
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.
Eligibility| Ages Eligible for Study: | 18 Years and older |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
Criteria
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.
Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01014208
Show 161 Study Locations
Contacts
| Contact: US GSK Clinical Trials Call Center | 877-379-3718 | GSKClinicalSupportHD@gsk.com |
Show 161 Study LocationsSponsors and Collaborators
GlaxoSmithKline
Investigators
| Study Director: | GSK Clinical Trials | GlaxoSmithKline |
More Information
No publications provided
| Responsible Party: | GlaxoSmithKline |
| ClinicalTrials.gov Identifier: | NCT01014208 History of Changes |
| Other Study ID Numbers: | 110928 |
| Study First Received: | November 4, 2009 |
| Last Updated: | May 16, 2013 |
| Health Authority: | United States: Institutional Review Board United States: Food and Drug Administration |
Keywords provided by GlaxoSmithKline:
|
Polish Lymphoma Research Group Japan Clinical Oncology Group refractory HOVON DHAP The All Ireland Cooperative Oncology Research Group Oncology Grupo Espanol de Linfomas ofatumumab Salvage chemotherapy DVD |
Nordic Lymphoma Group rituximab Autologous Stem Cell Transplant GELTAMO National Cancer Research Institute Lymphoma Clinical Studies Group safety Dutch-Belgian Cooperative Trial Group for Hematology-Oncology Genmab relapsed efficacy |
Additional relevant MeSH terms:
|
Lymphoma Lymphoma, B-Cell Lymphoma, Large B-Cell, Diffuse Neoplasms by Histologic Type Neoplasms Lymphoproliferative Disorders Lymphatic Diseases Immunoproliferative Disorders Immune System Diseases |
Lymphoma, Non-Hodgkin Rituximab Immunologic Factors Physiological Effects of Drugs Pharmacologic Actions Antirheumatic Agents Therapeutic Uses Antineoplastic Agents |
ClinicalTrials.gov processed this record on May 21, 2013