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

NCT ID: NCT03072771

Last Updated: 2023-11-28

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

14 participants

Study Classification

INTERVENTIONAL

Study Start Date

2017-08-01

Study Completion Date

2023-10-30

Brief Summary

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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.

Detailed Description

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Conditions

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Diffuse Large B Cell Lymphoma

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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ASCT + BEAM + Blinatumomab

* 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).

Group Type EXPERIMENTAL

Blinatumomab

Intervention Type DRUG

-Blinatumomab is a bispecific T cell engaging antibody

Autologous stem cell transplant

Intervention Type PROCEDURE

-Standard of care

Carmustine

Intervention Type DRUG

-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

Intervention Type DRUG

-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

Intervention Type DRUG

-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

Intervention Type DRUG

-Melphalan is an alkylating agent. It will be sourced from commercial supply. Institutional guidelines will be followed for storage, preparation, and administration of melphalan.

Peripheral blood draws

Intervention Type PROCEDURE

-Day +42, Day + 43, Day +56, and Day +100

Interventions

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Blinatumomab

-Blinatumomab is a bispecific T cell engaging antibody

Intervention Type DRUG

Autologous stem cell transplant

-Standard of care

Intervention Type PROCEDURE

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.

Intervention Type DRUG

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.

Intervention Type DRUG

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.

Intervention Type DRUG

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.

Intervention Type DRUG

Peripheral blood draws

-Day +42, Day + 43, Day +56, and Day +100

Intervention Type PROCEDURE

Other Intervention Names

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Blincyto ASCT auto-SCT BCNU BiCNU® VP16 Ara-C Cytosar-U ® 1-β-Arabinofuranosylcytosine Arabinosylcytosine Cytosine arabinoside Alkeran® Tablets Phenylalanine mustard

Eligibility Criteria

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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.

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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Amgen

INDUSTRY

Sponsor Role collaborator

Washington University School of Medicine

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Armin Ghobadi, M.D.

Role: PRINCIPAL_INVESTIGATOR

Washington University School of Medicine

Locations

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Washington University School of Medicine

St Louis, Missouri, United States

Site Status

Countries

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United States

References

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Ghobadi A, Foley NC, Cohen J, Rettig MP, Cashen AF, Gehrs L, Christ S, Street E, Wallace N, Ritchey J, Mehta-Shah N, Westervelt P, Fehniger TA, Kahl B, Bartlett NL, DiPersio JF. Blinatumomab consolidation post-autologous stem cell transplantation in patients with diffuse large B-cell lymphoma. Blood Adv. 2024 Feb 13;8(3):513-522. doi: 10.1182/bloodadvances.2023011130.

Reference Type DERIVED
PMID: 37871306 (View on PubMed)

Related Links

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http://www.siteman.wustl.edu

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

Other Identifiers

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201704108

Identifier Type: -

Identifier Source: org_study_id