Blinatumomab after Stem Cell Transplant in Treating Patients with Diffuse Large B-cell Lymphoma or Transformed Large Cell Lymphoma
This pilot phase I trial studies how well blinatumomab works after stem cell transplant in treating patients with diffuse large B-cell lymphoma or transformed large cell lymphoma. Blinatumomab is a monoclonal antibody that may interfere with the ability of tumor cells to grow and spread.
Inclusion Criteria
- PRE-ASCT ELIGIBILITY CRITERIA
- Histologically confirmed diagnosis of CD19 positive diffuse large B-cell lymphoma (DLBCL) or transformed large cell lymphoma from low grade lymphoma
- Chemo-sensitive (defined by complete response [CR] or partial response [PR] to most recent chemo regimen) based on pre-transplant positron emission tomography (PET) within 2 months of autologous transplant
- Patients with bulky disease are eligible for study provided that the patient not undergo radiation therapy until 30 days after the end of blinatumomab administration
- Available representative tissue (from fresh or formalin fixed paraffin embedded tissue) from the most recent biopsy or archival tumor tissue for clonotype evaluation for minimal residual disease (MRD) testing
- ELIGIBILITY CRITERIA TO BEGIN CONSOLIDATION THERAPY
- Performance status of Eastern Cooperative Oncology Group (ECOG) =< 2 or Karnofsky >= 60%
- Absence of clinically relevant central nervous system (CNS) pathology such as epilepsy, paresis, aphasia, stroke, severe brain injuries, dementia, or psychosis
- Absolute neutrophil count (ANC) >= 1,000
- Platelets >= 75,000
- Hemoglobin >= 8 g/dL
- Total bilirubin =< 1.5 x upper limit of normal (ULN) (unless related to Gilbert’s or Meulengracht’s syndrome)
- Alkaline phosphatase =< 3 x ULN
- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 3 x ULN
- Calculated or measured creatinine clearance >= 50 ml/min
Exclusion Criteria
- Chemotherapy (chemo)-resistant (defined by stable disease [SD] or progressive disease [PD] to most recent chemo regimen)
- Pregnant or breastfeeding
- Active CNS involvement of non-Hodgkin lymphoma (NHL)
- Clinically relevant CNS pathology such as epilepsy, childhood or adult seizure, paresis, aphasia, stroke, severe brain injuries, dementia, Parkinson’s disease, cerebellar disease, organic brain syndrome, or psychosis
- Prior stem cell transplant
- Concurrent hematologic or non-hematologic malignancy requiring treatment
- Human immunodeficiency virus (HIV) seropositive, or active hepatitis A, B, or C infection
- Uncontrolled congestive heart failure (CHF) or other comorbid systemic illnesses or severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens
Study sponsor and potential other locations can be found on ClinicalTrials.gov for NCT03072771.
PRIMARY OBJECTIVE:
I. To determine the feasibility and tolerability of blinatumomab consolidation post autologous (auto)-stem cell transplant (SCT) in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) (as measured by percentage of patients who can finish a full course of blinatumomab post auto-SCT).
SECONDARY OBJECTIVES:
I. To evaluate progression-free survival 1 year post auto-SCT.
II. To evaluate progression-free survival 3 years post-auto-SCT.
III. To evaluate overall survival 1 year post-auto-SCT.
IV. To evaluate overall survival 3 years post-auto-SCT.
V. To determine complete remission rate in patients with residual disease after auto-SCT.
EXPLORATORY OBJECTIVES:
I. To evaluate the immunopharmacologic effects of blinatumomab consolidation post auto-SCT in patients with DLBCL.
II. To evaluate the rate of cytokine release syndrome, systemic toxicities, and neurological complications in patients receiving blinatumomab after autologous stem cell transplant.
III. To detect molecular disease (minimal residual disease) by immunoglobulin high-throughput sequencing (Ig-HTS) from the acellular (plasma cell-free deoxyribonucleic acid [DNA]) compartments of peripheral blood before and after blinatumomab administration.
OUTLINE:
AUTO-SCT: Patients receive carmustine intravenously (IV) on day -7, etoposide IV twice daily (BID) on days -6 to -3, cytarabine IV BID on days -6 to -3, and melphalan on day -2. Patients then undergo auto-SCT on day 0.
CONSOLIDATION: Beginning 6 weeks after auto-SCT, patients receive blinatumomab IV continuously on days 42-70 in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 3 months for 1 year and then every 6 months for 2 years.
Trial PhasePhase I
Trial Typetreatment
Lead OrganizationSiteman Cancer Center at Washington University
Principal InvestigatorArmin Ghobadi
- Primary ID201704108
- Secondary IDsNCI-2017-00731
- ClinicalTrials.gov IDNCT03072771