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

NCT03072771 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: 201704108
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Diffuse Large B Cell Lymphoma

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (5)

• Progression-free survival (PFS)

  1 year post-auto-SCT

• Progression-free survival (PFS)

  3 years post-auto-SCT

• Overall survival

  1 year post-auto-SCT

• Overall survival

  3 years post-auto-SCT

• Complete remission rate in patients with residual disease after auto-SCT

  Up to Day 100

Study Arms (1)

ASCT + BEAM + Blinatumomab

EXPERIMENTAL

* 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).

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

Interventions

Blinatumomab DRUG

-Blinatumomab is a bispecific T cell engaging antibody

Also known as: Blincyto

ASCT + BEAM + Blinatumomab

Autologous stem cell transplant PROCEDURE

-Standard of care

Also known as: ASCT, auto-SCT

ASCT + BEAM + Blinatumomab

Carmustine 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.

Also known as: BCNU, BiCNU®

ASCT + BEAM + Blinatumomab

Etoposide 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.

Also known as: VP16

ASCT + BEAM + Blinatumomab

Cytarabine 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.

Also known as: Ara-C, Cytosar-U ®, 1-β-Arabinofuranosylcytosine, Arabinosylcytosine, Cytosine arabinoside

ASCT + BEAM + Blinatumomab

Melphalan 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.

Also known as: Alkeran® Tablets, Phenylalanine mustard

ASCT + BEAM + Blinatumomab

Peripheral blood draws PROCEDURE

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

ASCT + BEAM + Blinatumomab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Washington University School of Medicine: lead
• Amgen: collaborator

Study Sites (1)

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Related Publications (1)

• 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.

  PMID: 37871306 DERIVED

Related Links

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

MeSH Terms

Conditions

Lymphoma, Large B-Cell, Diffuse

Interventions

blinatumomab; Carmustine; Etoposide; Cytarabine; Melphalan

Condition Hierarchy (Ancestors)

Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Nitrosourea Compounds; Urea; Amides; Organic Chemicals; Nitroso Compounds; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Polycyclic Compounds; Glucosides; Glycosides; Carbohydrates; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins

Study Officials

• Armin Ghobadi, M.D.

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 2, 2017
• First Posted: March 7, 2017
• Study Start: August 1, 2017
• Primary Completion: April 7, 2021
• Study Completion: October 30, 2023
• Last Updated: November 28, 2023

Record last verified: 2023-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)