Trial Outcomes & Findings for Study of the BiTE® Blinatumomab (MT103) in Adult Patients With Relapsed/Refractory B-Precursor Acute Lymphoblastic Leukemia (ALL) (NCT NCT01209286)

NCT ID: NCT01209286

Last Updated: 2017-03-06

Results Overview

At the end of each infusion period, a bone marrow aspiration/biopsy was performed to evaluate the efficacy of blinatumomab. All hematological assessments of bone marrow were reviewed in a central reference laboratory. Hematological remissions were defined by the following criteria: Complete Response/Remission (CR): * Less than or equal to 5% blasts in the bone marrow * No evidence of circulating blasts or extramedullar disease * Full recovery of peripheral blood counts: * Platelets \> 100,000/μL * Hemoglobin ≥ 11 g/dL * Absolute neutrophil count (ANC) \> 1,500/μL Complete Remission with only Partial Hematological Recovery (CRh\*): * Less than or equal to 5% blasts in the bone marrow * No evidence of circulating blasts or extramedullar disease * Partial recovery of peripheral blood counts: * Platelets \> 50,000/μL * Hemoglobin ≥ 7 g/dL * ANC \> 500/μL.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

36 participants

Primary outcome timeframe

Within the first 2 cycles of treatment, 12 weeks

Results posted on

2017-03-06

Participant Flow

This study was open to adult patients with relapsed / refractory B-precursor acute lymphoblastic leukemia (ALL).

This ongoing study consisted of a core study of up to 33 weeks, efficacy follow-up until 24 months after treatment start and survival follow-up until 5 years after treatment start. Data are reported for the primary analysis conducted when the last participant completed the core study; data cutoff date of 15 October 2012.

Participant milestones

Participant milestones
Measure	Blinatumomab 15 μg Participants received blinatumomab 15 μg/m²/day as a continuous intravenous infusion at a constant flow rate over 4 weeks followed by a 2-week treatment-free interval for up to 5 consecutive cycles.	Blinatumomab 5/15 μg Participants received blinatumomab by continuous intravenous infusion over 4 weeks followed by a treatment-free interval of 2 weeks for up to 5 consecutive cycles. The initial dose was 5 μg/m²/day for the first seven days of treatment, followed by 15 μg/m²/day starting from Week 2 of treatment.	Blinatumomab 5/15/30 μg Participants received blinatumomab by continuous intravenous infusion over 4 weeks followed by a treatment-free interval of 2 weeks for up to 5 consecutive cycles. The initial dose was 5 μg/m²/day for the first seven days of treatment, a dose of 15 μg/m²/day in the subsequent 7 days, followed by 30 μg/m²/day starting from Week 3 of treatment.
Overall Study STARTED	7	23	6
Overall Study COMPLETED	2	13	3
Overall Study NOT COMPLETED	5	10	3

Reasons for withdrawal

Reasons for withdrawal
Measure	Blinatumomab 15 μg Participants received blinatumomab 15 μg/m²/day as a continuous intravenous infusion at a constant flow rate over 4 weeks followed by a 2-week treatment-free interval for up to 5 consecutive cycles.	Blinatumomab 5/15 μg Participants received blinatumomab by continuous intravenous infusion over 4 weeks followed by a treatment-free interval of 2 weeks for up to 5 consecutive cycles. The initial dose was 5 μg/m²/day for the first seven days of treatment, followed by 15 μg/m²/day starting from Week 2 of treatment.	Blinatumomab 5/15/30 μg Participants received blinatumomab by continuous intravenous infusion over 4 weeks followed by a treatment-free interval of 2 weeks for up to 5 consecutive cycles. The initial dose was 5 μg/m²/day for the first seven days of treatment, a dose of 15 μg/m²/day in the subsequent 7 days, followed by 30 μg/m²/day starting from Week 3 of treatment.
Overall Study Adverse Event	4	3	1
Overall Study Hematological Relapse After Remission	0	1	1
Overall Study Remission Not Achieved in 2 Cycles	1	3	1
Overall Study Physician Decision	0	2	0
Overall Study Other	0	1	0

Baseline Characteristics

Study of the BiTE® Blinatumomab (MT103) in Adult Patients With Relapsed/Refractory B-Precursor Acute Lymphoblastic Leukemia (ALL)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Blinatumomab 15 μg n=7 Participants Participants received blinatumomab 15 μg/m²/day as a continuous intravenous infusion at a constant flow rate over 4 weeks followed by a 2-week treatment-free interval for up to 5 consecutive cycles.	Blinatumomab 5/15 μg n=23 Participants Participants received blinatumomab by continuous intravenous infusion over 4 weeks followed by a treatment-free interval of 2 weeks for up to 5 consecutive cycles. The initial dose was 5 μg/m²/day for the first seven days of treatment, followed by 15 μg/m²/day starting from Week 2 of treatment.	Blinatumomab 5/15/30 μg n=6 Participants Participants received blinatumomab by continuous intravenous infusion over 4 weeks followed by a treatment-free interval of 2 weeks for up to 5 consecutive cycles. The initial dose was 5 μg/m²/day for the first seven days of treatment, a dose of 15 μg/m²/day in the subsequent 7 days, followed by 30 μg/m²/day starting from Week 3 of treatment.	Total n=36 Participants Total of all reporting groups
Age, Continuous	44.0 years STANDARD_DEVIATION 21.5 • n=5 Participants	38.1 years STANDARD_DEVIATION 16.7 • n=7 Participants	42.5 years STANDARD_DEVIATION 23.2 • n=5 Participants	40.0 years STANDARD_DEVIATION 18.4 • n=4 Participants
Sex: Female, Male Female	3 Participants n=5 Participants	9 Participants n=7 Participants	2 Participants n=5 Participants	14 Participants n=4 Participants
Sex: Female, Male Male	4 Participants n=5 Participants	14 Participants n=7 Participants	4 Participants n=5 Participants	22 Participants n=4 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) White	7 Participants n=5 Participants	22 Participants n=7 Participants	6 Participants n=5 Participants	35 Participants n=4 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Number of Prior Relapses 0	0 participants n=5 Participants	2 participants n=7 Participants	1 participants n=5 Participants	3 participants n=4 Participants
Number of Prior Relapses 1	5 participants n=5 Participants	15 participants n=7 Participants	3 participants n=5 Participants	23 participants n=4 Participants
Number of Prior Relapses 2	2 participants n=5 Participants	6 participants n=7 Participants	1 participants n=5 Participants	9 participants n=4 Participants
Number of Prior Relapses 3	0 participants n=5 Participants	0 participants n=7 Participants	1 participants n=5 Participants	1 participants n=4 Participants
Relapsed / refractory Status Primary Refractory	0 participants n=5 Participants	2 participants n=7 Participants	1 participants n=5 Participants	3 participants n=4 Participants
Relapsed / refractory Status Relapsed	7 participants n=5 Participants	21 participants n=7 Participants	5 participants n=5 Participants	33 participants n=4 Participants
Prior Allogeneic Hematopoietic Stem cell Transplantation (HSCT) Yes, Sibling	1 participants n=5 Participants	1 participants n=7 Participants	1 participants n=5 Participants	3 participants n=4 Participants
Prior Allogeneic Hematopoietic Stem cell Transplantation (HSCT) Yes, Unrelated	2 participants n=5 Participants	9 participants n=7 Participants	1 participants n=5 Participants	12 participants n=4 Participants
Prior Allogeneic Hematopoietic Stem cell Transplantation (HSCT) Yes, Haploidentical (mother/father)	0 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants	0 participants n=4 Participants
Prior Allogeneic Hematopoietic Stem cell Transplantation (HSCT) No prior allogeneic HSCT	4 participants n=5 Participants	13 participants n=7 Participants	4 participants n=5 Participants	21 participants n=4 Participants

PRIMARY outcome

Timeframe: Within the first 2 cycles of treatment, 12 weeks

Population: Full analysis set (FAS), defined as participants who received any infusion of the assigned study medication, who completed at least the first treatment cycle and for whom at least one response assessment was available after the start of treatment.

Outcome measures

Outcome measures
Measure	Blinatumomab 15 μg n=7 Participants Participants received blinatumomab 15 μg/m²/day as a continuous intravenous infusion at a constant flow rate over 4 weeks followed by a 2-week treatment-free interval for up to 5 consecutive cycles.	Blinatumomab 5/15 μg n=23 Participants Participants received blinatumomab by continuous intravenous infusion over 4 weeks followed by a treatment-free interval of 2 weeks for up to 5 consecutive cycles. The initial dose was 5 μg/m²/day for the first seven days of treatment, followed by 15 μg/m²/day starting from Week 2 of treatment.	Blinatumomab 5/15/30 μg n=6 Participants Participants received blinatumomab by continuous intravenous infusion over 4 weeks followed by a treatment-free interval of 2 weeks for up to 5 consecutive cycles. The initial dose was 5 μg/m²/day for the first seven days of treatment, a dose of 15 μg/m²/day in the subsequent 7 days, followed by 30 μg/m²/day starting from Week 3 of treatment.	Blinatumomab Overall n=36 Participants Participants received blinatumomab as a continuous intravenous infusion at a constant flow rate over 4 weeks followed by a 2-week treatment-free interval for up to 5 consecutive cycles.
Percentage of Participants With a Best Response of Complete Remission or Complete Remission With Only Partial Hematological Recovery Within 2 Cycles of Treatment	71.4 percentage of participants Interval 29.0 to 96.3	69.6 percentage of participants Interval 47.1 to 86.8	66.7 percentage of participants Interval 22.3 to 95.7	69.4 percentage of participants Interval 51.9 to 83.7

SECONDARY outcome

Timeframe: Within the first 2 cycles of treatment, 12 weeks

Population: Full analysis set

Outcome measures

Outcome measures
Measure	Blinatumomab 15 μg n=7 Participants Participants received blinatumomab 15 μg/m²/day as a continuous intravenous infusion at a constant flow rate over 4 weeks followed by a 2-week treatment-free interval for up to 5 consecutive cycles.	Blinatumomab 5/15 μg n=23 Participants Participants received blinatumomab by continuous intravenous infusion over 4 weeks followed by a treatment-free interval of 2 weeks for up to 5 consecutive cycles. The initial dose was 5 μg/m²/day for the first seven days of treatment, followed by 15 μg/m²/day starting from Week 2 of treatment.	Blinatumomab 5/15/30 μg n=6 Participants Participants received blinatumomab by continuous intravenous infusion over 4 weeks followed by a treatment-free interval of 2 weeks for up to 5 consecutive cycles. The initial dose was 5 μg/m²/day for the first seven days of treatment, a dose of 15 μg/m²/day in the subsequent 7 days, followed by 30 μg/m²/day starting from Week 3 of treatment.	Blinatumomab Overall n=36 Participants Participants received blinatumomab as a continuous intravenous infusion at a constant flow rate over 4 weeks followed by a 2-week treatment-free interval for up to 5 consecutive cycles.
Percentage of Participants With a Best Response of Complete Remission Within 2 Cycles of Treatment	14.3 percentage of participants Interval 0.4 to 57.9	43.5 percentage of participants Interval 23.2 to 65.5	66.7 percentage of participants Interval 22.3 to 95.7	41.7 percentage of participants Interval 25.5 to 59.2

SECONDARY outcome

Timeframe: Within the first 2 cycles of treatment, 12 weeks

Population: Full analysis set

At the end of each infusion period, a bone marrow aspiration/biopsy was performed to evaluate the efficacy of blinatumomab. All hematological assessments of bone marrow were reviewed in a central reference laboratory. Complete remission with only partial hematological recovery (CRh\*) was defined by the following criteria: * Less than or equal to 5% blasts in the bone marrow * No evidence of circulating blasts or extramedullar disease * Partial recovery of peripheral blood counts: * Platelets \> 50,000/μL * Hemoglobin ≥ 7 g/dL * ANC \> 500/μL.

Outcome measures

Outcome measures
Measure	Blinatumomab 15 μg n=7 Participants Participants received blinatumomab 15 μg/m²/day as a continuous intravenous infusion at a constant flow rate over 4 weeks followed by a 2-week treatment-free interval for up to 5 consecutive cycles.	Blinatumomab 5/15 μg n=23 Participants Participants received blinatumomab by continuous intravenous infusion over 4 weeks followed by a treatment-free interval of 2 weeks for up to 5 consecutive cycles. The initial dose was 5 μg/m²/day for the first seven days of treatment, followed by 15 μg/m²/day starting from Week 2 of treatment.	Blinatumomab 5/15/30 μg n=6 Participants Participants received blinatumomab by continuous intravenous infusion over 4 weeks followed by a treatment-free interval of 2 weeks for up to 5 consecutive cycles. The initial dose was 5 μg/m²/day for the first seven days of treatment, a dose of 15 μg/m²/day in the subsequent 7 days, followed by 30 μg/m²/day starting from Week 3 of treatment.	Blinatumomab Overall n=36 Participants Participants received blinatumomab as a continuous intravenous infusion at a constant flow rate over 4 weeks followed by a 2-week treatment-free interval for up to 5 consecutive cycles.
Percentage of Participants With a Best Response of Complete Remission With Only Partial Hematological Recovery Within 2 Cycles of Treatment	57.1 percentage of participants Interval 18.4 to 90.1	26.1 percentage of participants Interval 10.2 to 48.4	0.0 percentage of participants Interval 0.0 to 45.9	27.8 percentage of participants Interval 14.2 to 45.2

SECONDARY outcome

Timeframe: Within the first 2 cycles of treatment, 12 weeks

Population: Full analysis set

Outcome measures

Outcome measures
Measure	Blinatumomab 15 μg n=7 Participants Participants received blinatumomab 15 μg/m²/day as a continuous intravenous infusion at a constant flow rate over 4 weeks followed by a 2-week treatment-free interval for up to 5 consecutive cycles.	Blinatumomab 5/15 μg n=23 Participants Participants received blinatumomab by continuous intravenous infusion over 4 weeks followed by a treatment-free interval of 2 weeks for up to 5 consecutive cycles. The initial dose was 5 μg/m²/day for the first seven days of treatment, followed by 15 μg/m²/day starting from Week 2 of treatment.	Blinatumomab 5/15/30 μg n=6 Participants Participants received blinatumomab by continuous intravenous infusion over 4 weeks followed by a treatment-free interval of 2 weeks for up to 5 consecutive cycles. The initial dose was 5 μg/m²/day for the first seven days of treatment, a dose of 15 μg/m²/day in the subsequent 7 days, followed by 30 μg/m²/day starting from Week 3 of treatment.	Blinatumomab Overall n=36 Participants Participants received blinatumomab as a continuous intravenous infusion at a constant flow rate over 4 weeks followed by a 2-week treatment-free interval for up to 5 consecutive cycles.
Percentage of Participants With a Best Response of Partial Remission Within 2 Cycles of Treatment	0.0 percentage of participants Interval 0.0 to 41.0	8.7 percentage of participants Interval 1.1 to 28.0	0.0 percentage of participants Interval 0.0 to 45.9	5.6 percentage of participants Interval 0.7 to 18.7

SECONDARY outcome

Timeframe: During the core study treatment period (up to 30 weeks).

Population: Full analysis set (FAS)

A minimal residual disease (MRD) response is defined as MRD \< 10\^-4 blasts/nucleated cells based on polymerase chain reaction (PCR) evaluation of individual rearrangements of immunoglobulin or T cell receptor genes.

Outcome measures

Outcome measures
Measure	Blinatumomab 15 μg n=7 Participants Participants received blinatumomab 15 μg/m²/day as a continuous intravenous infusion at a constant flow rate over 4 weeks followed by a 2-week treatment-free interval for up to 5 consecutive cycles.	Blinatumomab 5/15 μg n=23 Participants Participants received blinatumomab by continuous intravenous infusion over 4 weeks followed by a treatment-free interval of 2 weeks for up to 5 consecutive cycles. The initial dose was 5 μg/m²/day for the first seven days of treatment, followed by 15 μg/m²/day starting from Week 2 of treatment.	Blinatumomab 5/15/30 μg n=6 Participants Participants received blinatumomab by continuous intravenous infusion over 4 weeks followed by a treatment-free interval of 2 weeks for up to 5 consecutive cycles. The initial dose was 5 μg/m²/day for the first seven days of treatment, a dose of 15 μg/m²/day in the subsequent 7 days, followed by 30 μg/m²/day starting from Week 3 of treatment.	Blinatumomab Overall n=36 Participants Participants received blinatumomab as a continuous intravenous infusion at a constant flow rate over 4 weeks followed by a 2-week treatment-free interval for up to 5 consecutive cycles.
Percentage of Participants With a Minimal Residual Disease (MRD) Response During the Core Study	71.4 percentage of participants Interval 29.0 to 96.3	73.9 percentage of participants Interval 51.6 to 89.8	50.0 percentage of participants Interval 11.8 to 88.2	69.4 percentage of participants Interval 51.9 to 83.7

SECONDARY outcome

Timeframe: Up to the data cut-off date of 15 October 2012; maximum follow up time was 459 days

Population: Full analysis set

The percentage of participants who underwent immediate allogeneic HSCT (defined as those in remission who undergo HSCT without receiving any other treatments) after having discontinued or completed the core study.

Outcome measures

Outcome measures
Measure	Blinatumomab 15 μg n=7 Participants Participants received blinatumomab 15 μg/m²/day as a continuous intravenous infusion at a constant flow rate over 4 weeks followed by a 2-week treatment-free interval for up to 5 consecutive cycles.	Blinatumomab 5/15 μg n=23 Participants Participants received blinatumomab by continuous intravenous infusion over 4 weeks followed by a treatment-free interval of 2 weeks for up to 5 consecutive cycles. The initial dose was 5 μg/m²/day for the first seven days of treatment, followed by 15 μg/m²/day starting from Week 2 of treatment.	Blinatumomab 5/15/30 μg n=6 Participants Participants received blinatumomab by continuous intravenous infusion over 4 weeks followed by a treatment-free interval of 2 weeks for up to 5 consecutive cycles. The initial dose was 5 μg/m²/day for the first seven days of treatment, a dose of 15 μg/m²/day in the subsequent 7 days, followed by 30 μg/m²/day starting from Week 3 of treatment.	Blinatumomab Overall n=36 Participants Participants received blinatumomab as a continuous intravenous infusion at a constant flow rate over 4 weeks followed by a 2-week treatment-free interval for up to 5 consecutive cycles.
Percentage of Participants Who Received an Allogeneic Hematopoietic Stem Cell Transplant (HSCT) After Treatment With Blinatumomab	42.9 percentage of participants	60.9 percentage of participants	16.7 percentage of participants	50.0 percentage of participants

SECONDARY outcome

Timeframe: Up to the data cut-off date of 15 October 2012; maximum follow up time was 459 days.

Population: Participants who reached complete remission or complete remission with partial hematological recovery during the core study.

Time to hematological relapse was measured for participants who achieved a CR or CRh\* during the core study and was measured from the time the participant first achieved remission until first documented relapse or death due to disease progression. Participants without a documented relapse (hematological or extramedullary) and who did not die were censored at the time of their last bone marrow assessment or their last survival follow-up visit confirming remission. Participants who died without having reported hematological relapse or without showing any clinical sign of disease progression were censored on their day of death. Hematological Relapse was defined as: * Proportion of blasts in bone marrow \> 5% * Extramedullary relapse. Time to hematological relapse was analyzed by Kaplan-Meier methods.

Outcome measures

Outcome measures
Measure	Blinatumomab 15 μg n=5 Participants Participants received blinatumomab 15 μg/m²/day as a continuous intravenous infusion at a constant flow rate over 4 weeks followed by a 2-week treatment-free interval for up to 5 consecutive cycles.	Blinatumomab 5/15 μg n=16 Participants Participants received blinatumomab by continuous intravenous infusion over 4 weeks followed by a treatment-free interval of 2 weeks for up to 5 consecutive cycles. The initial dose was 5 μg/m²/day for the first seven days of treatment, followed by 15 μg/m²/day starting from Week 2 of treatment.	Blinatumomab 5/15/30 μg n=4 Participants Participants received blinatumomab by continuous intravenous infusion over 4 weeks followed by a treatment-free interval of 2 weeks for up to 5 consecutive cycles. The initial dose was 5 μg/m²/day for the first seven days of treatment, a dose of 15 μg/m²/day in the subsequent 7 days, followed by 30 μg/m²/day starting from Week 3 of treatment.	Blinatumomab Overall n=25 Participants Participants received blinatumomab as a continuous intravenous infusion at a constant flow rate over 4 weeks followed by a 2-week treatment-free interval for up to 5 consecutive cycles.
Time to Hematological Relapse	240.0 days Interval 63.0 to 270.0	NA days Interval 227.0 to median was not reached during the core study	NA days Interval 15.0 to Median was not reached during the core study	270.0 days Interval 227.0 to Could not be estimated due to the low number of events

SECONDARY outcome

Timeframe: Up to the data cut-off date of 15 October 2012; maximum follow up time was 459 days.

Population: Participants who reached complete remission or complete remission with partial hematological recovery during the core study.

Relapse-free survival was measured only for participants who achieved a CR or CRh\* during the core study and was measured from the time the participant first achieved remission until first documented relapse or death due to any cause. Participants without a documented relapse (hematological or extramedullary) or who did not die were censored at the time of their last bone marrow assessment or their last survival follow-up visit confirming remission. Relapse-free survival was estimated using Kaplan-Meier methods.

Outcome measures

Outcome measures
Measure	Blinatumomab 15 μg n=5 Participants Participants received blinatumomab 15 μg/m²/day as a continuous intravenous infusion at a constant flow rate over 4 weeks followed by a 2-week treatment-free interval for up to 5 consecutive cycles.	Blinatumomab 5/15 μg n=16 Participants Participants received blinatumomab by continuous intravenous infusion over 4 weeks followed by a treatment-free interval of 2 weeks for up to 5 consecutive cycles. The initial dose was 5 μg/m²/day for the first seven days of treatment, followed by 15 μg/m²/day starting from Week 2 of treatment.	Blinatumomab 5/15/30 μg n=4 Participants Participants received blinatumomab by continuous intravenous infusion over 4 weeks followed by a treatment-free interval of 2 weeks for up to 5 consecutive cycles. The initial dose was 5 μg/m²/day for the first seven days of treatment, a dose of 15 μg/m²/day in the subsequent 7 days, followed by 30 μg/m²/day starting from Week 3 of treatment.	Blinatumomab Overall n=25 Participants Participants received blinatumomab as a continuous intravenous infusion at a constant flow rate over 4 weeks followed by a 2-week treatment-free interval for up to 5 consecutive cycles.
Relapse-free Survival	137.0 days Interval 63.0 to 270.0	268.0 days Interval 226.0 to 403.0	NA days Interval 15.0 to Median was not reached during the core study	233.0 days Interval 175.0 to 291.0

SECONDARY outcome

Timeframe: Up to the data cut-off date of 15 October 2012; maximum follow up time was 667 days.

Population: Full analysis set

Overall survival was measured for all participants from the date of first infusion of blinatumomab until the date of death due to any cause. Participants who did not die were censored on the last documented visit date. Overall survival was estimated using Kaplan-Meier methods.

Outcome measures

Outcome measures
Measure	Blinatumomab 15 μg n=7 Participants Participants received blinatumomab 15 μg/m²/day as a continuous intravenous infusion at a constant flow rate over 4 weeks followed by a 2-week treatment-free interval for up to 5 consecutive cycles.	Blinatumomab 5/15 μg n=23 Participants Participants received blinatumomab by continuous intravenous infusion over 4 weeks followed by a treatment-free interval of 2 weeks for up to 5 consecutive cycles. The initial dose was 5 μg/m²/day for the first seven days of treatment, followed by 15 μg/m²/day starting from Week 2 of treatment.	Blinatumomab 5/15/30 μg n=6 Participants Participants received blinatumomab by continuous intravenous infusion over 4 weeks followed by a treatment-free interval of 2 weeks for up to 5 consecutive cycles. The initial dose was 5 μg/m²/day for the first seven days of treatment, a dose of 15 μg/m²/day in the subsequent 7 days, followed by 30 μg/m²/day starting from Week 3 of treatment.	Blinatumomab Overall n=36 Participants Participants received blinatumomab as a continuous intravenous infusion at a constant flow rate over 4 weeks followed by a 2-week treatment-free interval for up to 5 consecutive cycles.
Overall Survival	269.0 days Interval 165.0 to 482.0	300.0 days Interval 254.0 to 431.0	NA days Interval 276.0 to Median was not reached during the core study	300.0 days Interval 258.0 to 455.0

SECONDARY outcome

Timeframe: From the start of the first infusion to 30 days after the end of the last infusion in the core study or from the start of the first retreatment cycle infusion to 30 days after the end of the last retreatment cycle; median treatment duration was 55.7 days.

Population: Safety analysis set, defined as all participants who received any infusion of blinatumomab.

Adverse events were evaluated for severity according to the grading scale provided in the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 3.0 and according to the following: Grade I (mild); Grade 2 (moderate); Grade 3 (severe - significantly limits the patient's ability to perform routine activities despite symptomatic therapy; Grade 4 (life-threatening); Grade 5 (death). The investigator used medical judgment to determine if there was a causal relationship (ie, certain, probable, possible, unlikely, not related) between an adverse event and blinatumomab. A serious adverse event is any untoward medical occurrence or effect, that at any dose: resulted in death, was life-threatening, required or prolonged hospitalization, resulted in persistent or significant disability or incapacity, is a congenital anomaly or birth defect or is a medically important condition.

Outcome measures

Outcome measures
Measure	Blinatumomab 15 μg n=7 Participants Participants received blinatumomab 15 μg/m²/day as a continuous intravenous infusion at a constant flow rate over 4 weeks followed by a 2-week treatment-free interval for up to 5 consecutive cycles.	Blinatumomab 5/15 μg n=23 Participants Participants received blinatumomab by continuous intravenous infusion over 4 weeks followed by a treatment-free interval of 2 weeks for up to 5 consecutive cycles. The initial dose was 5 μg/m²/day for the first seven days of treatment, followed by 15 μg/m²/day starting from Week 2 of treatment.	Blinatumomab 5/15/30 μg n=6 Participants Participants received blinatumomab by continuous intravenous infusion over 4 weeks followed by a treatment-free interval of 2 weeks for up to 5 consecutive cycles. The initial dose was 5 μg/m²/day for the first seven days of treatment, a dose of 15 μg/m²/day in the subsequent 7 days, followed by 30 μg/m²/day starting from Week 3 of treatment.	Blinatumomab Overall n=36 Participants Participants received blinatumomab as a continuous intravenous infusion at a constant flow rate over 4 weeks followed by a 2-week treatment-free interval for up to 5 consecutive cycles.
Number of Participants With Treatment-emergent Adverse Events Any adverse event (AE)	7 participants	23 participants	6 participants	36 participants
Number of Participants With Treatment-emergent Adverse Events Adverse events of at least CTC grade 3	7 participants	15 participants	5 participants	27 participants
Number of Participants With Treatment-emergent Adverse Events Treatment-related adverse events	7 participants	23 participants	6 participants	36 participants
Number of Participants With Treatment-emergent Adverse Events Related adverse events of at least CTC grade 3	7 participants	12 participants	4 participants	23 participants
Number of Participants With Treatment-emergent Adverse Events Serious adverse events	6 participants	13 participants	5 participants	24 participants
Number of Participants With Treatment-emergent Adverse Events Serious adverse events of at least CTC grade 3	6 participants	12 participants	4 participants	22 participants
Number of Participants With Treatment-emergent Adverse Events Serious related adverse events	4 participants	8 participants	4 participants	16 participants
Number of Participants With Treatment-emergent Adverse Events AEs leading to interruption of blinatumomab	3 participants	6 participants	3 participants	12 participants
Number of Participants With Treatment-emergent Adverse Events AEs leading to discontinuation of blinatumomab	4 participants	4 participants	1 participants	9 participants
Number of Participants With Treatment-emergent Adverse Events AEs leading to death	1 participants	4 participants	1 participants	6 participants

SECONDARY outcome

Timeframe: Samples were collected at predose and at 48 hours following start of infusion, when dose is escalated and on Days 8, 15, 22, and 29 of the first 2 cycles.

Population: Participants who received blinatumomab and who had available pharmacokinetic data.

The steady state concentration of blinatumomab was summarized as the observed concentrations collected at least 10 hours after the intravenous infusion was started for cycle 1 and cycle 2, respectively. Actual doses administered were used in the analysis. Concentrations below the limit of detection (3 pg/mL) were set to zero before data analysis and concentrations below the lower limit of quantitation (50 pg/mL) were excluded from analysis.

Outcome measures

Outcome measures
Measure	Blinatumomab 15 μg n=31 Participants Participants received blinatumomab 15 μg/m²/day as a continuous intravenous infusion at a constant flow rate over 4 weeks followed by a 2-week treatment-free interval for up to 5 consecutive cycles.	Blinatumomab 5/15 μg n=34 Participants Participants received blinatumomab by continuous intravenous infusion over 4 weeks followed by a treatment-free interval of 2 weeks for up to 5 consecutive cycles. The initial dose was 5 μg/m²/day for the first seven days of treatment, followed by 15 μg/m²/day starting from Week 2 of treatment.	Blinatumomab 5/15/30 μg n=5 Participants Participants received blinatumomab by continuous intravenous infusion over 4 weeks followed by a treatment-free interval of 2 weeks for up to 5 consecutive cycles. The initial dose was 5 μg/m²/day for the first seven days of treatment, a dose of 15 μg/m²/day in the subsequent 7 days, followed by 30 μg/m²/day starting from Week 3 of treatment.	Blinatumomab Overall Participants received blinatumomab as a continuous intravenous infusion at a constant flow rate over 4 weeks followed by a 2-week treatment-free interval for up to 5 consecutive cycles.
Steady State Blinatumomab Concentration	167 pg/mL Standard Deviation 66	553 pg/mL Standard Deviation 238	1180 pg/mL Standard Deviation 820	—

SECONDARY outcome

Timeframe: Samples were collected at predose and at 48 hours following start of infusion, when dose is escalated and on Days 8, 15, 22, and 29 of the first 2 cycles.

Population: Participants who received blinatumomab and who had available pharmacokinetic data.

Clearance was calculated as R0/Css; where R0 is the infusion rate (μg/m\^2/hr) and Css is the steady state concentration.

Outcome measures

Outcome measures
Measure	Blinatumomab 15 μg n=36 Participants Participants received blinatumomab 15 μg/m²/day as a continuous intravenous infusion at a constant flow rate over 4 weeks followed by a 2-week treatment-free interval for up to 5 consecutive cycles.	Blinatumomab 5/15 μg Participants received blinatumomab by continuous intravenous infusion over 4 weeks followed by a treatment-free interval of 2 weeks for up to 5 consecutive cycles. The initial dose was 5 μg/m²/day for the first seven days of treatment, followed by 15 μg/m²/day starting from Week 2 of treatment.	Blinatumomab 5/15/30 μg Participants received blinatumomab by continuous intravenous infusion over 4 weeks followed by a treatment-free interval of 2 weeks for up to 5 consecutive cycles. The initial dose was 5 μg/m²/day for the first seven days of treatment, a dose of 15 μg/m²/day in the subsequent 7 days, followed by 30 μg/m²/day starting from Week 3 of treatment.	Blinatumomab Overall Participants received blinatumomab as a continuous intravenous infusion at a constant flow rate over 4 weeks followed by a 2-week treatment-free interval for up to 5 consecutive cycles.
Clearance of Blinatumomab	1.34 L/m^2/hr Standard Deviation 0.61	—	—	—

SECONDARY outcome

Timeframe: Samples were collected prior to treatment start (baseline), and at 2, 6, 24, and 48 hours after drug infusion start, and at these same time points when dose is escalated in each treatment cycle.

Population: Participants who received blinatumomab and who had evaluable pharmacodynamic data.

The activation of immune effector cells was monitored by the measurement of peripheral blood cytokine levels including interleukin (IL)-2, IL-6, IL-10, tumor necrosis factor (TNF)-α and interferon gamma (IFN-γ) using multiplex cytometric bead assays. The lower limit of quantification (LLOQ) is 125 pg/mL and the limit of detection (LOD) is 20 pg/mL.

Outcome measures

Outcome measures
Measure	Blinatumomab 15 μg n=36 Participants Participants received blinatumomab 15 μg/m²/day as a continuous intravenous infusion at a constant flow rate over 4 weeks followed by a 2-week treatment-free interval for up to 5 consecutive cycles.	Blinatumomab 5/15 μg Participants received blinatumomab by continuous intravenous infusion over 4 weeks followed by a treatment-free interval of 2 weeks for up to 5 consecutive cycles. The initial dose was 5 μg/m²/day for the first seven days of treatment, followed by 15 μg/m²/day starting from Week 2 of treatment.	Blinatumomab 5/15/30 μg Participants received blinatumomab by continuous intravenous infusion over 4 weeks followed by a treatment-free interval of 2 weeks for up to 5 consecutive cycles. The initial dose was 5 μg/m²/day for the first seven days of treatment, a dose of 15 μg/m²/day in the subsequent 7 days, followed by 30 μg/m²/day starting from Week 3 of treatment.	Blinatumomab Overall Participants received blinatumomab as a continuous intravenous infusion at a constant flow rate over 4 weeks followed by a 2-week treatment-free interval for up to 5 consecutive cycles.
Serum Cytokine Peak Levels IL-6: Cycle 1 (N=35)	2563 pg/mL Standard Deviation 5231	—	—	—
Serum Cytokine Peak Levels IL-6: Cycle 2 (N=22)	212 pg/mL Standard Deviation 477	—	—	—
Serum Cytokine Peak Levels IL-6: Cycle 3 (N=11)	21 pg/mL Standard Deviation 26	—	—	—
Serum Cytokine Peak Levels IL-10: Cycle 1 (N=35)	1302 pg/mL Standard Deviation 2563	—	—	—
Serum Cytokine Peak Levels IL-10: Cycle 2 (N=22)	351 pg/mL Standard Deviation 582	—	—	—
Serum Cytokine Peak Levels IL-10: Cycle 3 (N=11)	419 pg/mL Standard Deviation 730	—	—	—
Serum Cytokine Peak Levels IFN-Ɣ: Cycle 1 (N=35)	467 pg/mL Standard Deviation 1824	—	—	—
Serum Cytokine Peak Levels IFN-Ɣ: Cycle 2 (N=22)	25 pg/mL Standard Deviation 28	—	—	—
Serum Cytokine Peak Levels IFN-Ɣ: Cycle 3 (N=11)	NA pg/mL Standard Deviation NA Data below detection level of the assay	—	—	—
Serum Cytokine Peak Levels IL-2: Cycle 1 (N=35)	36 pg/mL Standard Deviation 49	—	—	—
Serum Cytokine Peak Levels IL-2: Cycle 2 (N=22)	NA pg/mL Standard Deviation NA Data below detection level of the assay	—	—	—
Serum Cytokine Peak Levels IL-2: Cycle 3 (N=11)	NA pg/mL Standard Deviation NA Data below detection level of the assay	—	—	—
Serum Cytokine Peak Levels TNF-α: Cycle 1 (N=35)	60 pg/mL Standard Deviation 122	—	—	—
Serum Cytokine Peak Levels TNF-α: Cycle 2 (N=22)	NA pg/mL Standard Deviation NA Data below detection level of the assay	—	—	—
Serum Cytokine Peak Levels TNF-α: Cycle 3 (N=11)	NA pg/mL Standard Deviation NA Data below detection level of the assay	—	—	—

Adverse Events

Blinatumomab 15 μg

Serious events: 6 serious events

Other events: 7 other events

Deaths: 0 deaths

Blinatumomab 5/15 μg

Serious events: 13 serious events

Other events: 23 other events

Deaths: 0 deaths

Blinatumomab 5/15/30 μg

Serious events: 5 serious events

Other events: 6 other events

Deaths: 0 deaths

Blinatumomab Overall

Serious events: 24 serious events

Other events: 36 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Study Director

Amgen Inc.

Phone: 866-572-6436

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