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

Diffuse Large B Cell Lymphoma Clinical Trial

Official title:

A Pilot Trial of Blinatumomab Consolidation Post Autologous Stem Cell Transplantation in Patients With DLBCL

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03072771
• Other study ID #: 201704108
• Status: Completed
• Phase: Phase 1
• Start date: August 1, 2017
• Est. completion date: October 30, 2023

Study information

• Verified date: November 2023
• Source: Washington University School of Medicine
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 14
• Est. completion date: October 30, 2023
• Est. primary completion date: April 7, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Diffuse Large B Cell Lymphoma
• Lymphoma
• Lymphoma, B-Cell
• Lymphoma, Large B-Cell, Diffuse

Intervention

Drug:
• Blinatumomab
-Blinatumomab is a bispecific T cell engaging antibody

Procedure:
• Autologous stem cell transplant
-Standard of care

Drug:
• Carmustine
-Carmustine is an alkylating agent. It will be sourced from commercial supply. Institutional guidelines will be followed for storage, preparation, and administration of carmustine.
• Etoposide
-Etoposide is a semi-synthetic podophyllotoxin derivative. It will be sourced from commercial supply. Institutional guidelines will be followed for storage, preparation, and administration of etoposide.
• Cytarabine
-Cytarabine, commonly known as Ara-C, is a synthetic nucleoside. It will be sourced from commercial supply. Institutional guidelines will be followed for storage, preparation, and administration of cytarabine.
• Melphalan
-Melphalan is an alkylating agent. It will be sourced from commercial supply. Institutional guidelines will be followed for storage, preparation, and administration of melphalan.

Procedure:
• Peripheral blood draws
-Day +42, Day + 43, Day +56, and Day +100

Locations

Country	Name	City	State
United States	Washington University School of Medicine	Saint Louis	Missouri

Sponsors (2)

Lead Sponsor	Collaborator
Washington University School of Medicine	Amgen

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Feasibility and tolerability of blinatumomab consolidation post auto-SCT as measured by percentage of patients who can finish a full course of blinatumomab post-auto-SCT	-The primary endpoint is calculated by the proportion of patients who complete a full course of blinatumomab to the total number of patients started blinatumomab after auto-SCT.	Up to Day 70
Secondary	Progression-free survival (PFS)	-PFS is defined as from the date of Day 0 to date of progression or death, which occurs first. They are censored at the last follow-up otherwise.	1 year post-auto-SCT
Secondary	Progression-free survival (PFS)	-PFS is defined as from the date of Day 0 to date of progression or death, which occurs first. They are censored at the last follow-up otherwise.	3 years post-auto-SCT
Secondary	Overall survival	-OS is defined as from the date of Day 0 to date of death. They are censored at the last follow-up otherwise.	1 year post-auto-SCT
Secondary	Overall survival	-OS is defined as from the date of Day 0 to date of death. They are censored at the last follow-up otherwise.	3 years post-auto-SCT
Secondary	Complete remission rate in patients with residual disease after auto-SCT	-Complete remission=disappearance of all evidence of disease	Up to Day 100

External Links

•   Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine