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

• ClinicalTrials.gov Identifier: NCT03298412
• Recruitment Status: Terminated
• First Posted: October 2, 2017
• Results First Posted: September 11, 2020
• Last Update Posted: September 11, 2020
• Sponsor: Amgen
• Information provided by (Responsible Party): Amgen

• Study Type: Interventional
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: High-risk Diffuse Large B-cell Lymphoma
• Intervention: Drug: Blinatumomab
• Enrollment: 10

Participant Flow

Recruitment Details	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.
Pre-assignment Details	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.

Arm/Group Title	Blinatumomab
Arm/Group Description	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.
Period Title: Run-in Period
Started	10
Completed	1
Not Completed	9
Reason Not Completed
Other, Not Specified	1
Disease Progression	1
Ineligibility Determined	1
Decision by Sponsor	6
Period Title: Treatment Period
Started	1
Completed	1
Not Completed	0

Baseline Characteristics

Arm/Group Title		Blinatumomab
Arm/Group Description		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.
Overall Number of Baseline Participants		10
Baseline Analysis Population Description		All enrolled participants.
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	10 participants
		48.7 (18.4)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	10 participants
	Female	5 50.0%
	Male	5 50.0%
Race (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	10 participants
	American Indian or Alaska Native	0 0.0%
	Asian	1 10.0%
	Native Hawaiian or Other Pacific Islander	0 0.0%
	Black or African American	0 0.0%
	White	6 60.0%
	More than one race	0 0.0%
	Unknown or Not Reported	3 30.0%

Outcome Measures

1. Primary Outcome

Title	MRD-Negative Rate at the End of Cycle 1
Description	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)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Blinatumomab
Arm/Group Description:	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.
Overall Number of Participants Analyzed	1
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
	100; (2.5 to 100)

2. Secondary Outcome

Title	Kaplan-Meier Estimate: Progression-Free Survival (PFS)
Description	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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Blinatumomab
Arm/Group Description:	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.
Overall Number of Participants Analyzed	1
Median (95% Confidence Interval); Unit of Measure: months
	NA [1]; (NA to NA)

[1]

NA=Not estimable (1 participant in analysis set).

3. Secondary Outcome

Title	Kaplan-Meier Estimate: Duration of MRD-Negative Status
Description	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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Blinatumomab
Arm/Group Description:	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.
Overall Number of Participants Analyzed	1
Median (95% Confidence Interval); Unit of Measure: months
	10.26 [1]; (NA to NA)

[1]

NA=Not estimable (1 participant in analysis set).

4. Secondary Outcome

Title	Kaplan-Meier Estimate: Overall Survival (OS)
Description	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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Blinatumomab
Arm/Group Description:	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.
Overall Number of Participants Analyzed	1
Median (95% Confidence Interval); Unit of Measure: months
	NA [1]; (NA to NA)

[1]

NA=Not estimable (1 participant in analysis set).

5. Secondary Outcome

Title	Number of Participants With Treatment Emergent Adverse Events (TEAEs)
Description	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.

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Blinatumomab
Arm/Group Description:	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.
Overall Number of Participants Analyzed	1
Measure Type: Number; Unit of Measure: participants
Any TEAE	1
Grade 3 TEAE	1
Serious TEAE	0
TEAE Leading to Study Drug Discontinuation	0

Adverse Events

Time Frame	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.
Adverse Event Reporting Description	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.
Arm/Group Title	Blinatumomab
Arm/Group Description	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.
All-Cause Mortality
	Blinatumomab
	Affected / at Risk (%)
Total	0/10 (0.00%)
Serious Adverse Events
	Blinatumomab
	Affected / at Risk (%)
Total	0/1 (0.00%)
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Blinatumomab
	Affected / at Risk (%)
Total	1/1 (100.00%)
Blood and lymphatic system disorders
Neutropenia † 1	1/1 (100.00%)
1 Term from vocabulary, MedDRA 22.1; † Indicates events were collected by systematic assessment

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

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.

Results Point of Contact

• Name/Title: Study Director
• Organization: Amgen Inc.
• Phone: 866-572-6436
• EMail: medinfo@amgen.com

• Responsible Party: Amgen
• ClinicalTrials.gov Identifier: NCT03298412
• Other Study ID Numbers: 20150291; 2016-003255-30 ( EudraCT Number )
• First Submitted: September 12, 2017
• First Posted: October 2, 2017
• Results First Submitted: August 20, 2020
• Results First Posted: September 11, 2020
• Last Update Posted: September 11, 2020