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

Primary Purpose

Diffuse Large B Cell Lymphoma

Status

Active

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

Blinatumomab

Autologous stem cell transplant

Carmustine

Etoposide

Cytarabine

Melphalan

Peripheral blood draws

About this trial

This is an interventional treatment trial for Diffuse Large B Cell Lymphoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Washington University School of Medicine

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

ASCT + BEAM + Blinatumomab

Arm 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).

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.

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.

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.

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.

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

-Complete remission=disappearance of all evidence of disease

Full Information

NCT ID

NCT03072771

First Posted

March 2, 2017

Last Updated

May 8, 2023

Sponsor

Washington University School of Medicine

Collaborators

Amgen

1. Study Identification

Unique Protocol Identification Number

NCT03072771

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

May 2023

Overall Recruitment Status

Active, not recruiting

Study Start Date

August 1, 2017 (Actual)

Primary Completion Date

April 7, 2021 (Actual)

Study Completion Date

November 25, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Washington University School of Medicine

Collaborators

Amgen

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Diffuse Large B Cell Lymphoma

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

14 (Actual)

8. Arms, Groups, and Interventions

Arm Title

ASCT + BEAM + Blinatumomab

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

Blinatumomab

Other Intervention Name(s)

Blincyto

Intervention Description

-Blinatumomab is a bispecific T cell engaging antibody

Intervention Type

Procedure

Intervention Name(s)

Autologous stem cell transplant

Other Intervention Name(s)

ASCT, auto-SCT

Intervention Description

-Standard of care

Intervention Type

Drug

Intervention Name(s)

Carmustine

Other Intervention Name(s)

BCNU, BiCNU®

Intervention Description

-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

Intervention Name(s)

Etoposide

Other Intervention Name(s)

VP16

Intervention Description

-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

Intervention Name(s)

Cytarabine

Other Intervention Name(s)

Ara-C, Cytosar-U ®, 1-β-Arabinofuranosylcytosine, Arabinosylcytosine, Cytosine arabinoside

Intervention Description

-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

Intervention Name(s)

Melphalan

Other Intervention Name(s)

Alkeran® Tablets, Phenylalanine mustard

Intervention Description

-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

Procedure

Intervention Name(s)

Peripheral blood draws

Intervention Description

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

Primary Outcome Measure Information:

Title

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

Description

-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.

Time Frame

Up to Day 70

Secondary Outcome Measure Information:

Title

Progression-free survival (PFS)

Description

-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.

Time Frame

1 year post-auto-SCT

Title

Progression-free survival (PFS)

Description

-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.

Time Frame

3 years post-auto-SCT

Title

Overall survival

Description

-OS is defined as from the date of Day 0 to date of death. They are censored at the last follow-up otherwise.

Time Frame

1 year post-auto-SCT

Title

Overall survival

Description

-OS is defined as from the date of Day 0 to date of death. They are censored at the last follow-up otherwise.

Time Frame

3 years post-auto-SCT

Title

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

Description

-Complete remission=disappearance of all evidence of disease

Time Frame

Up to Day 100

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility 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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Armin Ghobadi, M.D.

Organizational Affiliation

Washington University School of Medicine

Official's Role

Principal Investigator

Facility Information:

Facility Name

Washington University School of Medicine

City

Saint Louis

State/Province

Missouri

ZIP/Postal Code

63110

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

Links:

URL

http://www.siteman.wustl.edu

Description

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

Learn more about this trial

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

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