The goal of this clinical trial is to show that incorporating ofatumumab instead of rituximab in combination with etoposide and cytarabine (OVA) is successful in collecting autologous stem cells for use in an autologous stem cell transplantation (autoSCT) and to examine its effectiveness in eliminating residual diffuse large B-Cell Lymphoma (DLBCL) in patients.
Patients with relapsed Diffuse Large B-cell Lymphoma (DLBCL) who are refractory to or relapse within 12 months of first-line rituximab-based therapy, have poor outcomes with conventional approaches to autologous stem cell transplantation as detailed above. The investigators hypothesize that the intensive mobilization strategy developed can overcome some of the obstacles to successful autologous stem cell transplantation (ASCT) by both eliminating residual disease following salvage therapy and by facilitating stem cell collection. Even though there is clinical experience in the cooperative group setting with intensive pre-ASCT mobilization, it has never been prospectively validated in DLBCL and concerns exist as to its ability to improve outcomes with ASCT in this high-risk, and heavily pretreated group of patients. Furthermore, most patients in the study site's registry treated with intensive mobilization were rituximab-naïve and the findings may not translate in the rituximab-refractory population. The investigators also believe that ofatumumab, a novel monoclonal antibody against a distinct cluster of differentiation antigen 20 (CD20) epitope may in fact overcome rituximab resistance in DLBCL patients and through more effective complement dependent cytotoxicity (CDC) may eliminate minimal residual disease in the patient and contaminating tumor cells in the stem cell graft. General Design This is a single-institution, single-arm, prospective phase II study. Patients with high-risk DLBCL (defined as either achieving less than complete remission (CR) to initial rituximab-containing therapy or relapsing within 12 months of initial therapy) will be enrolled on this study and will undergo staging prior to receiving intensive mobilization with ofatumumab, etoposide, and high-dose ara-C (OVA). Following successful stem cell collection, patients will proceed to standard autologous transplantation with cyclophosphamide, 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU), and etoposide (CBV) preparative regimen. Response evaluation will occur after salvage therapy, following intensive mobilization therapy (d42), at day +90 after ASCT, and at 6, 12 and 24 months thereafter. Event-free, progression-free, and overall survival will also be assessed until 48 months. The primary study endpoint is mobilization-adjusted complete metabolic response rate (maCR) following OVA. Subjects who are not chemosensitive to salvage therapy (i.e. do not achieve a partial response or complete response) will be re-evaluated after an additional salvage regimen. If they are still not chemosensitive at this point, they will be withdrawn from the study and replaced.
1000 mg IV days 0, 7, 14, 21
10 mg/Kg IV over 24 hours daily, days 1-4
2000 mg/m2 IV twice daily, days 1-4
University of California, San Francisco
San Francisco, California, United States
Number of Patients Achieving Complete Response (CR) to the Treatment Upon Successful Stem Cell Mobilization
CR will be calculated based on the PET/CT scan following 2 cycles of salvage therapy using the revised International Working Group (IWG) Criteria for a lymphoma response. This includes: Complete disappearance of all detectable clinical evidence of disease and disease-related symptoms if present before therapy, Post-treatment residual mass of any size is permitted as long as it is PET-, Spleen and/or liver, if enlarged before therapy based on physical exam or CT scan, should not be palpable on physical exam and should be considered normal size by imaging studies, and nodules related to lymphoma should disappear, If bone marrow was involved by lymphoma before treatment, infiltrate must have cleared on repeat bone marrow biopsy. Biopsy sample must be adequate (with goal of \> 20 mm unilateral core). If sample is indeterminate by morphology, it should be negative by immunohistochemistry. A sample that is negative by immunohistochemistry but demonstrates small population of clonal l
Time frame: Day 42
Number of Patients Achieving Mobilization-adjusted Complete Response (maCR)
Number of patients achieving maCR to the treatment upon successful stem cell mobilization, defined as at least 2 x10\^6 cluster of differentiation 34 (CD34)+cells/Kg of actual body weight. Patients who require use of plerixafor or an autologous bone marrow harvest are considered mobilization failures and will be treated as non-responders.
Time frame: Day 42
Number of Patients Who Received OVA and Then Met Criteria to Proceed to ASCT and Achieved a CR/Partial Response (PR) Post-ASCT
Determination of CR or PR must meet the revised International Working Group (IWG) Criteria for lymphoma response
Time frame: Up to 5 months
Number of Patients Who Advance From Partial Response (PR) to Complete (CR)
Fluorodeoxyglucose-positron emission tomography (FDG-PET) conversion rate was used determined the number of participants who improved following OVA Treatment.
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Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
19
Time frame: Up to 5 months
Number of Participants With Successful Neutrophil Engraftments
Neutrophil engraftment is defined as the first day of 3 consecutive days with absolute neutrophil count of \>500 cells/microlitre (uL). Response evaluation will occur at day +90 after ASCT, and at 6, 12 and 24 months thereafter
Time frame: Up to 24 months after ASCT
Number of Participants With Successful Platelet Engraftments
Platelet engraftment is defined as the first of three consecutive measurements for which the platelet count was \> 20,000/uL, and must be at least 24 hours following the last platelet transfusion. Response evaluation will occur at day +90 after ASCT, and at 6, 12 and 24 months after ASCT
Time frame: Up to 24 months after ASCT
Median Time to Progression
Time to progression (TTP) is defined as the time from treatment after OVA until documented lymphoma progression or receipt of anti-lymphoma therapy (except for planned post-ASCT radiotherapy) or death due to lymphoma. Patients are to be censored at the time of last followup or death due to another cause
Time frame: Up to 48 months
Progression Free Survival Rate
The percentage of participants in the study still alive at time of censoring. The time frame defined as the time from day 0 of OVA treatment until lymphoma progression, receipt of anti-lymphoma therapy (except for planned post-ASCT radiotherapy), or death as a result of any cause. Patients will be censored at the time of median follow-up.
Time frame: Up to 24 months
Overall Survival Rate (OS)
The percentage of participants in the study still alive at time of censoring. The time frame is defined as the time from day 0 of OVA treatment until death as a result of any cause. Patients will be censored at the time of last followup
Time frame: Up to 24 months