Diffuse Large Cell Lymphoma Relapsed/Refractory Clinical Trial
Official title:
A Phase II Study of Intensive Consolidation and Stem Cell Mobilization Therapy With Ofatumumab, Etoposide, and High-dose Ara-C (OVA), Followed by Autologous Stem Cell Transplantation in High-risk Patients With Relapsed/Refractory Diffuse Large B-Cell Lymphoma
| Verified date | June 2022 |
| Source | University of California, San Francisco |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | |
| Study type | Interventional |
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.
| Status | Completed |
| Enrollment | 19 |
| Est. completion date | July 1, 2021 |
| Est. primary completion date | July 6, 2017 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 18 Years and older |
| Eligibility | Inclusion Criteria: - Diagnosis of refractory or relapsed biopsy-proven CD20+ diffuse large B-cell lymphoma or primary mediastinal B-cell lymphoma. - Age 18 years or older - Refractory to or relapse following a rituximab/anthracycline first-line regimen - High-risk disease as defined by one of the following: - First relapse after CR within 12 months of initiation of front-line therapy - Less than CR to front-line therapy - Second-line age-adjusted International Prognostic Index score (sAAIPI) of 1 or higher at the time of relapse - Receipt of no more than three prior chemotherapy regimens. Monoclonal antibody therapy alone and involved field radiotherapy are not included in this number. Prior use of ofatumumab is allowed if there has been no disease progression following that therapy (i.e. ofatumumab-based salvage regimens are allowed) - Eastern Cooperative Oncology Group (ECOG) performance status = 2. Eligibility to proceed to OVA - Chemosensitive disease as defined by at least a partial response to salvage therapy by positron emission tomography/computed tomography (PET/CT) criteria. - Bone marrow with less than 15% lymphoma cells following salvage therapy. No evidence of myelodysplasia. - Patients must have adequate organ function with serum creatinine <2.0 mg/dL, total bilirubin =2 times the upper limit of normal (ULN), and aspartate aminotransferase (AST) =3 times the ULN. - Neutrophils >1,000/µL and platelets >100,000/µL prior to day 0 - No active uncontrolled infection. Eligibility to proceed to CBV ASCT - Patients must be out of the hospital after OVA for a minimum of 4 weeks. - Adequate peripheral blood stem cell collection with cluster of differentiation 34 (CD34) cell dose =2 X 106 /kg (actual body weight). - No evidence of disease progression on day 42 assessment - Approved by the University of California, San Francisco (UCSF) Bone Marrow Transplant Committee to proceed with ASCT. Exclusion Criteria - Presence of disease transformation from a previously diagnosed low-grade lymphoma - Progression following prior ofatumumab-based therapy - Active central nervous system or meningeal involvement by lymphoma. Patients with a history of central nervous system (CNS) or meningeal involvement must be in a documented remission by cerebrospinal fluid (CSF) evaluation and contrast MRI imaging for at least 3 months prior to study entry. - Evidence of myelodysplasia on any bone marrow biopsy. - Treatment with any known non-marketed drug substance or experimental therapy within 5 terminal half-lives or 4 weeks prior to enrollment, whichever is longer, or currently participating in any other interventional clinical study. - Other past or current malignancy. Subjects who have been free of malignancy for at least 3 years, or have a history of completely resected non-melanoma skin cancer, or successfully treated in situ carcinoma are eligible. - Chronic or current infectious disease requiring systemic antibiotics, antifungal, or antiviral treatment such as, but not limited to, chronic renal infection, chronic chest infection with bronchiectasis, tuberculosis and active Hepatitis C. - History of significant cerebrovascular disease in the past 6 months or ongoing event with active symptoms or sequelae - Known HIV infection - Clinically significant cardiac disease including unstable angina, acute myocardial infarction within six months prior to randomization, congestive heart failure (NYHA III-IV), and arrhythmia unless controlled by therapy, with the exception of extra systoles or minor conduction abnormalities. - Significant concurrent, uncontrolled medical condition including, but not limited to, renal, hepatic, gastrointestinal, endocrine, pulmonary, neurological, cerebral or psychiatric disease which in the opinion of the investigator may represent a risk for the patient. - Positive serology for Hepatitis B (HB) defined as a positive test for HbsAg and a detectable hepatitis B virus (HBV) DNA viral load. If negative for HBsAg but HBcAb positive (regardless of HBsAb status), a HBV DNA test will be performed and if positive the subject will be excluded. If HBV DNA is negative, subject may be included but must undergo at least every 2-month HBV DNA polymerase chain reaction (PCR) testing from the start of treatment during the treatment course. Prophylactic antiviral therapy may be initiated at the discretion of the investigator. - Positive serology for hepatitis C (HC) defined as a positive test for hepatitis C antibody (HCAb), in which case reflexively perform a hepatitis C virus (HCV) PCR to confirm the result - Pregnant or lactating women. Women of childbearing potential must have a negative pregnancy test at screening. - Women of childbearing potential, including women whose last menstrual period was less than one year prior to screening, unable or unwilling to use adequate contraception from study start to one year after the last dose of protocol therapy. Adequate contraception is defined as hormonal birth control, intrauterine device, double barrier method or total abstinence. - Male subjects unable or unwilling to use adequate contraception methods from study start to one year after the last dose of protocol therapy. - Subjects who have received live virus vaccination within the 4 weeks prior to planned initiation of study treatment. |
| Country | Name | City | State |
|---|---|---|---|
| United States | University of California, San Francisco | San Francisco | California |
| Lead Sponsor | Collaborator |
|---|---|
| C. Babis Andreadis | GlaxoSmithKline, University of California, San Francisco |
United States,
Kambhampati S, Hunter B, Varnavski A, Fakhri B, Kaplan L, Ai WZ, Pampaloni M, Huang CY, Martin T 3rd, Damon L, Andreadis CB. Ofatumumab, Etoposide, and Cytarabine Intensive Mobilization Regimen in Patients with High-risk Relapsed/Refractory Diffuse Large B-Cell Lymphoma Undergoing Autologous Stem Cell Transplantation. Clin Lymphoma Myeloma Leuk. 2021 Apr;21(4):246-256.e2. doi: 10.1016/j.clml.2020.11.005. Epub 2020 Nov 11. — View Citation
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | 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 | Day 42 | |
| Primary | 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. | Day 42 | |
| Secondary | 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 | Up to 5 months | |
| Secondary | 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. | Up to 5 months | |
| Secondary | 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 | Up to 24 months after ASCT | |
| Secondary | 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 | Up to 24 months after ASCT | |
| Secondary | 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 | Up to 48 months | |
| Secondary | 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. | Up to 24 months | |
| Secondary | 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 | Up to 24 months |