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

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ClinicalTrials.gov Identifier: NCT03072771
Recruitment Status : Recruiting
First Posted : March 7, 2017
Last Update Posted : May 21, 2020
Sponsor:
Collaborator:
Amgen
Information provided by (Responsible Party):
Washington University School of Medicine

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.


Condition or disease Intervention/treatment Phase
Diffuse Large B Cell Lymphoma Drug: Blinatumomab Procedure: Autologous stem cell transplant Drug: Carmustine Drug: Etoposide Drug: Cytarabine Drug: Melphalan Procedure: Peripheral blood draws Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 15 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Pilot Trial of Blinatumomab Consolidation Post Autologous Stem Cell Transplantation in Patients With DLBCL
Actual Study Start Date : August 1, 2017
Estimated Primary Completion Date : December 31, 2020
Estimated Study Completion Date : December 31, 2023


Arm Intervention/treatment
Experimental: 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).
Drug: Blinatumomab
-Blinatumomab is a bispecific T cell engaging antibody
Other Name: Blincyto

Procedure: Autologous stem cell transplant
-Standard of care
Other Names:
  • ASCT
  • auto-SCT

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.
Other Names:
  • BCNU
  • BiCNU®

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.
Other Name: VP16

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.
Other Names:
  • Ara-C
  • Cytosar-U ®
  • 1-β-Arabinofuranosylcytosine
  • Arabinosylcytosine
  • Cytosine arabinoside

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.
Other Names:
  • Alkeran® Tablets
  • Phenylalanine mustard

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




Primary Outcome Measures :
  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 [ Time Frame: Up to Day 100 (4 week infusion schedule) or Day 128 (8 week infusion schedule) ]
    -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 :
  1. Progression-free survival (PFS) [ Time Frame: 1 year post-auto-SCT ]
    -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.

  2. Progression-free survival (PFS) [ Time Frame: 3 years post-auto-SCT ]
    -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. Overall survival [ Time Frame: 1 year post-auto-SCT ]
    -OS is defined as from the date of Day 0 to date of death. They are censored at the last follow-up otherwise.

  4. Overall survival [ Time Frame: 3 years post-auto-SCT ]
    -OS is defined as from the date of Day 0 to date of death. They are censored at the last follow-up otherwise.

  5. Complete remission rate in patients with residual disease after auto-SCT [ Time Frame: Up to Day 100 (4 week infusion schedule) or Day 128 (8 week infusion schedule) ]
    -Complete remission=disappearance of all evidence of disease



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03072771


Contacts
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Contact: Armin Ghobadi, M.D. 314-747-2743 arminghobadi@wustl.edu

Locations
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United States, Missouri
Washington University School of Medicine Recruiting
Saint Louis, Missouri, United States, 63110
Contact: Armin Ghobadi, M.D.    314-747-2743    arminghobadi@wustl.edu   
Principal Investigator: Armin Ghobadi, M.D.         
Sponsors and Collaborators
Washington University School of Medicine
Amgen
Investigators
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Principal Investigator: Armin Ghobadi, M.D. Washington University School of Medicine
Additional Information:
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Responsible Party: Washington University School of Medicine
ClinicalTrials.gov Identifier: NCT03072771    
Other Study ID Numbers: 201704108
First Posted: March 7, 2017    Key Record Dates
Last Update Posted: May 21, 2020
Last Verified: May 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Additional relevant MeSH terms:
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Lymphoma
Lymphoma, B-Cell
Lymphoma, Large B-Cell, Diffuse
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, Non-Hodgkin
Cytarabine
Etoposide
Melphalan
Carmustine
Blinatumomab
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Antimetabolites
Antiviral Agents
Anti-Infective Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents, Alkylating
Alkylating Agents