Effect of Blinatumomab on Minimal Residual Disease (MRD) in Diffuse Large B-Cell Lymphoma (DLBCL) Subjects Post Autologous Hematopoietic Stem Cell Transplantation (aHSCT)

NCT ID: NCT03298412

Last Updated: 2020-09-11

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 10 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-05-23
• Study Completion Date: 2019-09-30

Brief Summary

The study will estimate the MRD-negative response rate after treatment with blinatumomab in subjects with high-risk DLBCL who are MRD-positive following aHSCT. The clinical hypothesis is that the MRD-negative response rate will be greater than 10%. Achieving an MRD-negative response rate of 30% would be of scientific and clinical interest.

Detailed Description

This is a phase 2, multicenter, open-label, single arm estimation study in adult subjects with high-risk DLBCL in complete remission. The study will consist of up to a 28-day screening period, a run-in period of up to 24 months, a 12-week treatment period (8 weeks of blinatumomab treatment followed by a 4-week treatment free period), a 30-day safety follow-up visit after the last dose of blinatumomab, and a long-term follow-up period that begins after the safety follow-up visit is completed until 1 year from the first dose of blinatumomab. The study will enroll approximately 90 subjects in the screening period with biopsy proven, high-risk DLBCL that are positron emission tomography-computer tomography (PET-CT) negative 90 days (± 30 days) post aHSCT. During the run-in period subjects will be followed by clinic visits at regular interval for up to 24 months for monitoring of MRD status in plasma by a next generation sequencing (NGS)-based assay. It is estimated 30 subjects will be either MRD-positive at screening or become MRD-positive during the 24-month run-in period. The number of subjects enrolled may be altered in order to ensure that approximately 30 subjects are assigned to treatment with blinatumomab. Enrollment may be stopped, once approximately 30 subjects have been assigned to treatment with blinatumomab.

Conditions

High-risk Diffuse Large B-cell Lymphoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Blinatumomab

After a run-in period of up to 24 months to evaluate MRD status and assess eligibility for treatment assignment, participants received blinatumomab intravenous (IV) infusion at an initial dose of 9 μg/day for the first 7 days of treatment, escalated (dose-step) to 28 μg/day starting on Day 8 (Week 2), followed by a dose-step to 112 μg/day starting on Day 15 (Week 3) and continuing until completion of therapy (Day 57 of Cycle 1).

Cycle 1 of blinatumomab treatment is 12 weeks (84 days) in duration and includes 8 weeks (56 days) of blinatumomab IV infusion followed by a 4-week (28-day) treatment-free interval.

Group Type: EXPERIMENTAL

Blinatumomab

Intervention Type: DRUG

Blinatumomab is administered as a continuous IV infusion.

Interventions

Blinatumomab

Blinatumomab is administered as a continuous IV infusion.

Intervention Type: DRUG

Other Intervention Names

BLINCYTO; AMG 103

Eligibility Criteria

Inclusion Criteria

• Subject has provided informed consent prior to initiation of any study-specific activities/procedures or subject's legally acceptable representative has provided informed consent prior to any study-specific activities/procedures being initiated when the subject has any kind of condition that, in the opinion of the investigator, may compromise the ability of the subject to give written informed consent.
• Age ≥ 18 at time of informed consent
• Biopsy-proven DLBCL excluding DLBCL that represents transformation of indolent non-Hodgkin's lymphoma (NHL) Note: Lymphoblastic Lymphoma and Burkitt Lymphoma histology are not eligible
• Subject has ≥ 1 characteristic feature of high-risk DLBCL:

• High-risk first complete remission (defined as interim positron emission tomography - computed tomography (PET-CT) positive or < complete remission to frontline chemotherapy AND achieved complete remission to platinum-containing salvage)
• Relapse within 1 year of diagnosis
• Secondary age-adjusted international prognostic index > 1
• Partial response/partial metabolic response after minimum of 2 cycles of platinum-containing salvage chemotherapy
• C-myc rearrangement
• aHSCT with high-dose chemotherapy following first (or later) salvage treatment.
• PET-CT negative (Deauville score ≤ 3) 90 days (± 30 days) post aHSCT
• Available relapsed and/or diagnostic pathology formalin-fixed paraffin-embedded (FFPE) tumor block or slide samples at the time of enrollment including the successful identification of malignant clone sequences by the central laboratory.
• MRD plasma sample collected ≤ 3 weeks after the post aHSCT PET-CT scan
• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.
• Adequate organ function determined ≤ 3 weeks prior to enrollment defined as follows:

• Hematological:

Absolute neutrophil count (ANC) ≥ 1.0 x 109/L Platelet count ≥ 75 x 109/L Hemoglobin ≥ 8 g/dL

• Renal:

Creatinine clearance ≥ 50 mL/min Cockcroft-Gault equation

• Hepatic:

Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 3 x upper limit of normal (ULN) Total bilirubin < 2 x ULN (unless Gilbert's Disease or if liver involvement with lymphoma)

• Subject will be available to complete all protocol-required study visits or procedures, and/or to comply with all required study procedures to the best of the subject's and investigator's knowledge including but not limited to:
• Completion of up to a 24-month run-in period
• Completion of all regularly scheduled study visits including blood draws for MRD assessment, clinical disease state assessment, PET-CT scans (ie, at time of MRD positivity or relapse), assignment to treatment with blinatumomab

• MRD-positive assessment (by NGS analysis) at enrollment or at any time during the run-in 1 period
• PET-CT negative (defined by Deauville criteria ≤ 3) at run-in 2 performed ≤ 3 weeks from MRD test result available to the site at run-in 1. Historical PET-CT are allowed if performed ≤ 6 weeks from day 1 (first dose of blinatumomab) and subject has no clinical signs or symptoms suggestive of disease progression (eg, increase in lactate dehydrogenase [LDH] not otherwise explained)
• Adequate organ function determined ≤ 7 days prior to treatment assignment with blinatumomab as follows:

• Hematological:

ANC ≥ 1.0 x 109/L Hemoglobin ≥ 8 g/L Platelet count ≥ 75 x 109/L

• Renal:

Creatinine clearance ≥ 50 mL/min Cockcroft-Gault equation

• Hepatic:

AST and ALT < 3 x ULN Total bilirubin < 2 x ULN (unless Gilbert's Disease or if liver involvement with lymphoma)

Exclusion Criteria

• Clinically relevant central nervous system (CNS) pathology such as epilepsy, seizure, paresis, aphasia,stroke, severe brain injury, dementia, Parkinson's disease, cerebellar disease, organic brain syndrome, and psychosis
• Evidence of CNS involvement with DLBCL at disease evaluation obtained prior to starting blinatumomab
• Current autoimmune disease or history of autoimmune disease with potential of CNS involvement
• Prior anti-CD19 directed therapies
• Prior alloHSCT
• Received radiation ≤ 2 weeks prior to enrollment
• Infection with human immunodeficiency virus or chronic infection with hepatitis B virus (hepatitis B surface antigen positive) or hepatitis C virus (anti-hepatitis C virus positive)
• History of malignancy other than DLBCL within the past 3 years with the following exceptions:

• Malignancy treated with curative intent and with no known active disease present for ≥ 3 years before enrollment and felt to be at low risk for recurrence by the treating physician
• Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease
• Adequately treated cervical carcinoma in situ without evidence of disease
• Adequately treated breast ductal carcinoma in situ without evidence of disease
• Prostatic intraepithelial neoplasia without evidence of prostate cancer
• Adequately treated urothelial papillary noninvasive carcinoma or carcinoma in situ
• Subject has known hypersensitivity to immunoglobulins or any of the products or components to be administered during dosing.
• History or evidence of any other clinically significant disorder, condition or disease (with the exception of those outlined above) that, in the opinion of the investigator or Amgen physician, if consulted, would pose a risk to subject safety or interfere with the study evaluation, procedures or completion.
• Women who are pregnant or breastfeeding or planning to become pregnant or breastfeed while receiving blinatumomab and for an additional 48 hours after the last treatment dose of blinatumomab. (Females of child bearing potential should only be included after a negative highly sensitive urine or serum pregnancy test.)
• Women of childbearing potential unwilling to use an acceptable method of effective contraception while receiving blinatumomab and for an additional 48 hours after last dose of blinatumomab. Note: The pregnancy, breastfeeding and contraceptive requirements are specific to blinatumomab. The investigator is responsible for providing the subject (male and female) with pregnancy and breastfeeding (female only) avoidance requirements for other medications given during the study.
• Currently receiving treatment in another investigational device or drug study or less than 30 days since ending treatment on another investigational device or drug study. Other investigational procedures while participating in this study are excluded.

• Subject has active infection requiring systemic therapy
• Any change in the part 1 eligibility criteria during the run-in period.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 100 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Amgen

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

MD

Role: STUDY_DIRECTOR

Amgen

Locations

Research Site

Atlanta, Georgia, United States

Research Site

Maywood, Illinois, United States

Research Site

Cleveland, Ohio, United States

Research Site

Dallas, Texas, United States

Research Site

St Leonards, New South Wales, Australia

Research Site

Westmead, New South Wales, Australia

Research Site

Clayton, Victoria, Australia

Research Site

Geelong, Victoria, Australia

Research Site

Charleroi, , Belgium

Research Site

Leuven, , Belgium

Research Site

Liège, , Belgium

Research Site

Créteil, , France

Research Site

Lille, , France

Research Site

Marseille, , France

Research Site

Montpellier, , France

Research Site

Paris, , France

Research Site

Pessac, , France

Research Site

Pierre-Bénite, , France

Research Site

Rouen, , France

Research Site

Athens, , Greece

Research Site

Athens, , Greece

Research Site

Thessaloniki, , Greece

Research Site

Bergamo, , Italy

Research Site

Brescia, , Italy

Research Site

Florence, , Italy

Research Site

Milan, , Italy

Research Site

Palermo, , Italy

Research Site

Torino, , Italy

Research Site

Bellinzona, , Switzerland

Research Site

Bern, , Switzerland

Research Site

Lausanne, , Switzerland

Research Site

Zurich, , Switzerland

Countries

United States; Australia; Belgium; France; Greece; Italy; Switzerland

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

http://www.amgentrials.com

AmgenTrials clinical trials website

Other Identifiers

2016-003255-30

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

20150291

Identifier Type: -

Identifier Source: org_study_id