Overview

This trial is active, not recruiting.

Condition lymphoma, large-cell, diffuse
Treatments ofatumumab + dhap, rituximab + dhap
Phase phase 3
Sponsor GlaxoSmithKline
Start date March 2010
End date February 2014
Trial size 447 participants
Trial identifier NCT01014208, 110928

Summary

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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification safety/efficacy study
Intervention model parallel assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
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.
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)
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.
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.

Primary Outcomes

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)

Secondary Outcomes

Measure
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)
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)
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)
Overall survival (OS)
time frame: From randomization to death due to any cause (assessed for up to 5 years)
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)
Number of participants completing autologous stem cell transplant (ASCT)
time frame: Approximately 4 to 6 weeks following Cycle 3 (assessed up to 3 months)
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])
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])
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)
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)

Eligibility Criteria

Male or female participants at least 18 years old.

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.

Additional Information

Official title Ofatumumab Versus Rituximab Salvage Chemoimmunotherapy Followed by Autologous Stem Cell Transplant (ASCT) in Relapsed or Refractory Diffuse Large B Cell Lymphoma (DLBCL)
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.
Trial information was received from ClinicalTrials.gov and was last updated in October 2014.
Information provided to ClinicalTrials.gov by GlaxoSmithKline.