Blinatumomab Consolidation Post Autologous Stem Cell Transplantation in Patients With Diffuse Large B-Cell Lymphoma (DLBCL)

The Washington University

Status and phase: Completed; Phase 1

Conditions: Diffuse Large B Cell Lymphoma

Treatments: Procedure: Peripheral blood draws; Drug: Melphalan; Drug: Blinatumomab; Drug: Carmustine; Drug: Cytarabine; Drug: Etoposide; Procedure: Autologous stem cell transplant

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT03072771

201704108

Details and patient eligibility

About

Based on the further need to improve progression-free survival (PFS) and overall survival (OS) post autologous stem cell transplant (SCT) for DLBCL, the hematopoietic profile of patients following auto-SCT, the activity of blinatumomab in DLBCL and its favorable toxicity profile, the investigators propose a pilot study to test blinatumomab as consolidation therapy post auto-SCT for patients with DLBCL.

The investigators hypothesize the blinatumomab consolidation will optimize the effector to target (E-T) ratio and aid in the eradication of remaining tumor cells, leading to decreased relapse and increased overall survival. In addition, since tumor burden will be at a minimum, infusional toxicities including neurologic toxicities may also be limited. The purpose of this pilot study is to study the feasibility and tolerability of blinatumomab consolidation post auto-SCT for patients with chemo-sensitive DLBCL undergoing auto-SCT.

Enrollment: 14 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Pre-ASCT Inclusion Criteria

• At least 18 years of age
• 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 remission (CR) or partial remission (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.

Pre-ASCT Exclusion Criteria

• Chemo-resistant (defined by stable disease (SD) or progressive disease (PD) to most recent chemo regimen)
• Pregnant or breastfeeding
• Active central nervous system (CNS) involvement of Non-Hodgkin's 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
• 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.

Eligibility Criteria to Begin Consolidation Therapy

• A participant must meet all of the following criteria on Day +42 visit in order to continue on the study to begin consolidation therapy with blinatumomab.

• Performance status of Eastern Cooperative Oncology Group (ECOG) ≤ 2 or Karnofsky ≥ 60 %

• Absence of clinically relevant CNS pathology such as epilepsy, paresis, aphasia, stroke, sever brain injuries, dementia, or psychosis

• Required clinical laboratory values:

  • 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 ≤ 5 x ULN
  • ALT and AST ≤ 5 x ULN
  • Calculated or measured creatinine clearance ≥ 50ml/min

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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14 participants in 1 patient group

ASCT + BEAM + Blinatumomab

Experimental group

Description:

* Standard of care ASCT with BEAM conditioning (carmustine/etoposide/cytarabine/melphalan) - guidelines below, other conditionings are allowed: * carmustine is typically given intravenously (IV) at a dose of 300 mg/m\^2 on Day -7 * etoposide is typically given IV at a dose of 100 mg/m\^2 twice per day (BID) on Days -6, -5, -4, and -3 (8 doses) * cytarabine is typically given IV at a dose of 100 mg/m\^2 BID on Days -6, -5, -4, and -3 (8 doses) * melphalan is typically given IV at a dose of 140 mg/m\*2 on Day -2 * Auto-SCT will take place on Day 0 as per institutional guidelines * Consolidation with blinatumomab will start 6 weeks following auto-SCT. Patients with CR or PR based on pre-transplant PET/CT will receive blinatumomab as a continuous IV infusion (CIVI) at 9μg/day for 1 week, then 28μg/day for 3 weeks (total of 4 weeks).

Treatment:

Procedure: Autologous stem cell transplant

Procedure: Peripheral blood draws

Drug: Cytarabine

Drug: Etoposide

Drug: Carmustine

Drug: Blinatumomab

Drug: Melphalan