Trial Outcomes & Findings for Effect of Blinatumomab on Minimal Residual Disease (MRD) in Diffuse Large B-Cell Lymphoma (DLBCL) Subjects Post Autologous Hematopoietic Stem Cell Transplantation (aHSCT) (NCT NCT03298412)

Results Overview

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).

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

10 participants

Primary outcome timeframe

12 weeks (84 days)

Results posted on

2020-09-11

Participant Flow

The study enrolled participants from Australia, France, Greece, Italy, Switzerland, and the United States. The first participant enrolled on 23 May 2018, and the last participant enrolled on 05 August 2019.

The study included a Screening period (up to 28 days), and a run-in period of up to 24 months to evaluate minimal residual disease (MRD) status and assess eligibility for treatment assignment.

Participant milestones

Participant milestones
Measure	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.
Run-in Period STARTED	10
Run-in Period COMPLETED	1
Run-in Period NOT COMPLETED	9
Treatment Period STARTED	1
Treatment Period COMPLETED	1
Treatment Period NOT COMPLETED	0

Reasons for withdrawal

Reasons for withdrawal
Measure	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.
Run-in Period Other, Not Specified	1
Run-in Period Disease Progression	1
Run-in Period Ineligibility Determined	1
Run-in Period Decision by Sponsor	6

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Blinatumomab n=10 Participants 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.
Age, Continuous	48.7 years STANDARD_DEVIATION 18.4 • n=5 Participants
Sex: Female, Male Female	5 Participants n=5 Participants
Sex: Female, Male Male	5 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	1 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants
Race (NIH/OMB) White	6 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	3 Participants n=5 Participants

PRIMARY outcome

Timeframe: 12 weeks (84 days)

Population: Full analysis set (all participants who received any infusion of blinatumomab).

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).

Outcome measures

Outcome measures
Measure	Blinatumomab n=1 Participants 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.
MRD-Negative Rate at the End of Cycle 1	100 percentage of participants Interval 2.5 to 100.0

SECONDARY outcome

Timeframe: up to 1 year from first dose of blinatumomab

Population: Full analysis set (all participants who received any infusion of blinatumomab).

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.

Outcome measures

Outcome measures
Measure	Blinatumomab n=1 Participants 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.
Kaplan-Meier Estimate: Progression-Free Survival (PFS)	NA months NA=Not estimable (1 participant in analysis set).

SECONDARY outcome

Timeframe: up to 1 year from first dose of blinatumomab

Population: Full analysis set (all participants who received any infusion of blinatumomab).

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.

Outcome measures

Outcome measures
Measure	Blinatumomab n=1 Participants 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.
Kaplan-Meier Estimate: Duration of MRD-Negative Status	10.26 months NA=Not estimable (1 participant in analysis set).

SECONDARY outcome

Timeframe: up to 1 year from first dose of blinatumomab

Population: Full analysis set (all participants who received any infusion of blinatumomab).

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.

Outcome measures

Outcome measures
Measure	Blinatumomab n=1 Participants 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.
Kaplan-Meier Estimate: Overall Survival (OS)	NA months NA=Not estimable (1 participant in analysis set).

SECONDARY outcome

Timeframe: 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.

Population: Full Analysis Set: all participants who received at least 1 dose of blinatumomab.

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).

Outcome measures

Outcome measures
Measure	Blinatumomab n=1 Participants 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.
Number of Participants With Treatment Emergent Adverse Events (TEAEs) Any TEAE	1 participants
Number of Participants With Treatment Emergent Adverse Events (TEAEs) Grade 3 TEAE	1 participants
Number of Participants With Treatment Emergent Adverse Events (TEAEs) Serious TEAE	0 participants
Number of Participants With Treatment Emergent Adverse Events (TEAEs) TEAE Leading to Study Drug Discontinuation	0 participants

Adverse Events

Blinatumomab

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Blinatumomab n=1 participants at risk 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.
Blood and lymphatic system disorders Neutropenia	100.0% 1/1 • All-cause mortality was collected from enrollment through 24 months of run-in period among participants who did not receive study drug, or through 1 year after the first dose of study drug, or end of study. SAEs/AEs were collected 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. All-cause mortality is reported for all participants enrolled in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.

Additional Information

Study Director

Amgen Inc.

Phone: 866-572-6436

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The Clinical Trial Agreement generally does not restrict an investigator's discussion of trial results after completion. The Agreement permits Amgen a limited period of time to review material discussing trial results (typically up to 45 days and possible extension). Amgen may remove confidential information, but authors have final control and approval of publication content. For multicenter studies, the investigator agrees not to publish any results before the first multi-center publication.
Publication restrictions are in place

Restriction type: OTHER