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

NCT03072771

Description:

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.

Related Conditions:
  • Diffuse Large B-Cell Lymphoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • 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

Clinical Trial IDs

  • ORG STUDY ID: 201704108
  • NCT ID: NCT03072771

Conditions

  • Diffuse Large B Cell Lymphoma

Interventions

DrugSynonymsArms
BlinatumomabBlincytoASCT + BEAM + Blinatumomab
CarmustineBCNU, BiCNU®ASCT + BEAM + Blinatumomab
EtoposideVP16ASCT + BEAM + Blinatumomab
CytarabineAra-C, Cytosar-U ®, 1-β-Arabinofuranosylcytosine, Arabinosylcytosine, Cytosine arabinosideASCT + BEAM + Blinatumomab
MelphalanAlkeran® Tablets, Phenylalanine mustardASCT + BEAM + Blinatumomab

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
ASCT + BEAM + BlinatumomabExperimentalStandard of care ASCT with BEAM conditioning (carmustine/etoposide/cytarabine/melphalan) - guidelines below: 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).
  • Blinatumomab
  • Carmustine
  • Etoposide
  • Cytarabine
  • Melphalan

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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure: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)
Safety Issue:
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.

Secondary Outcome Measures

Measure:Progression-free survival (PFS)
Time Frame:1 year post-auto-SCT
Safety Issue:
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.
Measure:Progression-free survival (PFS)
Time Frame:3 years post-auto-SCT
Safety Issue:
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.
Measure:Overall survival
Time Frame:1 year post-auto-SCT
Safety Issue:
Description:-OS is defined as from the date of Day 0 to date of death. They are censored at the last follow-up otherwise.
Measure:Overall survival
Time Frame:3 years post-auto-SCT
Safety Issue:
Description:-OS is defined as from the date of Day 0 to date of death. They are censored at the last follow-up otherwise.
Measure: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)
Safety Issue:
Description:-Complete remission=disappearance of all evidence of disease

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Washington University School of Medicine

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