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.
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.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
10
Blinatumomab is administered as a continuous IV infusion.
Research Site
Atlanta, Georgia, United States
MRD-Negative Rate at the End of Cycle 1
The estimated MRD-negative rate, calculated as the percentage of participants with MRD-negative status after treatment with blinatumomab. MRD-negative status was assessed by positron emission tomography-computed tomography (PET-CT) or computed tomography (CT).
Time frame: 12 weeks (84 days)
Kaplan-Meier Estimate: Progression-Free Survival (PFS)
PFS, calculated as the time from the date of first dose of blinatumomab until the date of diagnosis of relapse of lymphoma (by PET-CT, CT, clinical assessment or relapse biopsy, whichever was the preferred method), or date of death, whichever was earliest. Participants who were alive and who did not have progression or new anti-tumor treatment (excluding any stem cell transplantation) were to be censored at last date of tumor assessment.
Time frame: up to 1 year from first dose of blinatumomab
Kaplan-Meier Estimate: Duration of MRD-Negative Status
The duration of MRD-negative status, assessed only in participants who achieve MRD-negative status after blinatumomab treatment, was defined as the time when a negative MRD result was first established until documented MRD-positive re-occurrence, disease progression or, death due to any cause. Participants without any of these events at the time of the analysis were to be censored at their last disease assessment date. MRD-negative status was assessed by PET-CT or CT.
Time frame: up to 1 year from first dose of blinatumomab
Kaplan-Meier Estimate: Overall Survival (OS)
OS, defined as time from the first dose of blinatumomab treatment until death due to any cause. Participants still alive at the time of the analysis were censored at date last known to be alive.
Time frame: up to 1 year from first dose of blinatumomab
Number of Participants With Treatment Emergent Adverse Events (TEAEs)
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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
...and 22 more locations
An adverse event (AE) is defined as any untoward medical occurrence. A serious AE is defined as an AE that is: fatal; life threatening; requires in-patient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; a congenital anomaly/birth defect; other medically important serious event. TEAEs are events with an onset after the administration of the first dose of blinatumomab treatment through 30 days after the end of blinatumomab treatment. Events were graded according to the Common Terminology Criteria for Adverse Events (CTCAE): Grade 1 (mild), Grade 2 (moderate), Grade 3 (severe), Grade 4 (life-threatening), Grade 5 (death).
Time frame: From first dose of study drug through 30 days after the last dose of study drug. The treatment duration for the participant who received blinatumomab was 57 days.