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

GlaxoSmithKline (GSK)

Status and phase: Completed; Phase 3

Conditions: Lymphoma, Large-Cell, Diffuse

Treatments: Drug: OFATUMUMAB + DHAP; Drug: RITUXIMAB + DHAP

Study type: Interventional

Funder types: Industry

Identifiers

NCT01014208

110928

Details and patient eligibility

About

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.

Full 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.

Enrollment: 447 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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447 participants in 2 patient groups

OFATUMUMAB + DHAP CHEMOTHERAPY REGIMEN

Experimental group

Description:

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.

Treatment:

Drug: OFATUMUMAB + DHAP

RITUXIMAB + DHAP CHEMOTHERAPY REGIMEN

Active Comparator group

Description:

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.

Treatment:

Drug: RITUXIMAB + DHAP