Intensive Consolidation and Stem Cell Mobilization Therapy Followed by Autologous Stem Cell Transplantation in High-risk Patients With Relapsed/Refractory Diffuse Large B-Cell Lymphoma
Condition: Diffuse Large Cell Lymphoma Relapsed/Refractory
MeSH terms: Lymphoma; Lymphoma, Large B-Cell, Diffuse
Intervention: Ofatumumab; Etoposide; Cytarabine
Intervention description: 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
Intervention MeSH terms: Cytarabine; Etoposide; Ofatumumab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 19.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: relapsed; refractory; DLBCL; lymphoma; B-cell; diffuse

Summary:

      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.
    

Eligibility criteria:

        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.