Study to Evaluate Safety and Efficacy of Blinatumomab in Subjects With Relapsed/Refractory (R/R) Aggressive B-Cell NHL

• Sponsor: Amgen (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02910063
• Collaborator: (none)
• Enrollment: 41
• Locations: 31
• Arm: 1
• Actual Duration (Months): 37.6
• Patients Per Site: 1.3
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

This is a phase 2/3 open label, multicenter trial testing blinatumomab monotherapy for the treatment of subjects with Relapsed/Refractory (R/R) aggressive B-NHL not achieving CMR after 2 cycles of standard platinum-based chemotherapy regimens administered as S1. This study incorporates multiple interim analyses for futility, efficacy, and unblinded sample-size re-estimation. In the phase 3 part of the study, blinatumomab will be compared to Investigator's Choice chemotherapy.

In March 2019, decision made to not proceed with phase 3.

Condition or Disease	Intervention/Treatment	Phase
B-Cell Non Hodgkin Lymphoma	Drug: Blinatumomab	Phase 2/Phase 3

Detailed Description

This is a phase 2/3 open label, multicenter trial testing blinatumomab monotherapy for the treatment of subjects with R/R aggressive B-NHL not achieving CMR after standard platinum-based chemotherapy regimens administered as S1. This study incorporates multiple interim analyses for futility, efficacy, and unblinded sample-size re-estimation. In the phase 3 part of the study, blinatumomab will be compared to IC chemotherapy.The phase 2 component of the study will consist of up to a 28-day screening period, approximately 70 to 112 days of study treatment, a 30-day (+/- 3days) safety follow up, and long-term follow up that will conclude with the final analysis of the phase 3 component, estimated at 30 months after initiation of the phase 3 component. For the phase 3 component, the study will consist of up to a 28-day screening period, a treatment period of up to approximately 168 days, a 30-day safety follow-up visit, and long-term follow up. Long-term follow up will conclude with the final analysis.In the phase 2 component, enrolled subjects will receive blinatumomab monotherapy. In the phase 3 component, enrolled subjects will be randomized in a 1:1 ratio to blinatumomab or IC chemotherapy.

In March 2019, decision made to not proceed with phase 3.

Study Design

• Study Type: Interventional
• Actual Enrollment: 41 participants
• Allocation: N/A
• Intervention Model: Sequential Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 2/3 Multi-center Study to Evaluate the Safety and Efficacy of Blinatumomab in Subjects With Relapsed/Refractory Aggressive B-Cell Non Hodgkin Lymphoma
• Actual Study Start Date: Jan 23, 2017
• Actual Primary Completion Date: Mar 12, 2020
• Actual Study Completion Date: Mar 12, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Blinatumomab Blinatumomab is administered as a continuous intravenous infusion (CIVI). A single cycle of blinatumomab is continuous infusion with step dosing of 9 µg/day x 7 days, 28 µg/day x 7 days, and 112 µg/days until the end of the cycle.	Drug: Blinatumomab; Blinatumomab monotherapy; Other Names: AMG 103 Blincyto

Outcome Measures

Primary Outcome Measures

1. Phase 2: Percentage of Participants Who Achieved Complete Metabolic Response (CMR) [Up to 12 weeks after first dose of blinatumomab]

   Complete metabolic response (CMR) was determined by central radiographic assessment of positron emission tomography and computed tomography (PET/CT) scans using the Lugano Classification.

2. Phase 3: Number of Participants Who Achieved Complete Metabolic Response (CMR) [Up to 12 weeks after first dose of study treatment]

   Complete metabolic response (CMR) was determined by central radiographic assessment of positron emission tomography and computed tomography (PET/CT) scans using the Lugano Classification.

Secondary Outcome Measures

1. Phase 2: Overall Survival (OS) [From randomization until the end of study, up to 30 months]

   OS was defined as the time from the date of randomization until death due to any cause. OS was calculated using Kaplan-Meier estimates.

2. Phase 2: Objective Response Rate (ORR) [Up to 12 weeks after first dose of blinatumomab]

   ORR is inclusive of all participants who achieved CMR or those who achieved partial metabolic response (PMR), as determined by central radiographic assessment of PET/CT scans using the Lugano Classification.

3. Phase 2: Progression Free Survival (PFS) [From first dose of blinatumomab until the end of study, up to 30 months]

   PFS was defined as the time from start of treatment with blinatumomab until the date of diagnosis of progression of lymphoma, or date of death, whichever is earliest. PFS was estimated using Kaplan-Meier method.

4. Phase 2: Duration of Response (DOR) [From first dose of blinatumomab up to 12 weeks]

   DOR was calculated only for participants who achieve a response (CMR or PMR). The duration was calculated from the date a response, CMR or PMR, was first achieved until the earliest date of a disease assessment indicating disease progression or death, whichever occured first. DOR was estimated using Kaplan-Meier method.

5. Phase 2: Percentage of Participants Who Experienced Successful Mobilization [From first dose of blinatumomab until the end of study, up to 30 months]

   Successful mobilization rate was defined as the percentage of participants who initiated mobilization while in remission and without any other anti-tumor therapy where the mobilization procedure had an outcome of 'Successful'. Successful mobilization was dictated by institutional standards and defined when the target cell dose was no less than 2 x 10^6 CD34+ cells/kg.

6. Phase 2: Percentage of Participants Who Had Allogeneic or Autologous Post-baseline Hematopoietic Stem Cell Transplant (HSCT) [From baseline HSCT until the end of study, up to 30 months]

   The percentage of responders per investigator's review (participants who achieved either CMR or PMR during the treatment) who have undergone allogeneic (allo) HSCT or autologous (auto) HSCT while in remission and without any other anti-cancer treatment.

7. Phase 2: Cumulative Incidence Function Estimate of 100-day Mortality After HSCT Presented as Percentage of Participants That Died Not Due to Relapse, With Relapse and Death Due to Relapse as Competing Events [100 days after HSCT]

   Non-relapse mortality rate at 100 days after HSCT was calculated as the percentage of participants who died not due to relapse. Only participants who achieved a response per investigator's review and underwent autoHSCT are included.

8. Phase 2: Blinatumomab Steady State Concentrations (Css) [Pre-dose on Day 1, and post-dose on Days 2, 9 and 16 of Cycle 1 (Cycle 1 was 70 days)]

   Pharmacokinetic (PK) parameters were estimated by non compartmental analysis. The Css of blinatumomab was summarized as the observed concentrations collected after at least 24 hours after the start of continuous IV infusion or start of dose step, where appropriate.

9. Phase 2: Blinatumomab Clearance (CL) [Pre-dose on Day 1, and post-dose on Days 2, 9 and 16 of Cycle 1 (Cycle 1 was 70 days)]

   Serum blinatumomab CL was calculated as CL=R0/Css,DN; where R0 is the infusion rate (μg/hr) and Css,DN is the dose normalized average Css. For the CL calculation, the Css,DN was normalized to the 112 μg/day dose in which the value of dose in units of μg/hr was used for the infusion rate.

10. Phase 2: Half-life of Blinatumomab [Pre-dose on Day 1, and Days 2, 9 and 16 of Cycle 1 (Cycle 1 was 70 days)]

11. Phase 2: Number of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE) [From first dose of blinatumomab until 30 days after last dose. The maximum treatment duration for blinatumomab was 114 days]

    Treatment-emergent adverse events were events with an onset after the administration of the first dose of blinatumomab. TEAEs were graded using the Common Terminology Criteria for Adverse Events (CTCAE). Grade 2 Moderate; minimal, local or noninvasive intervention indicated; limited age appropriate instrumental activities of daily life (ADL). Grade 3 Severe or medically significant but not immediately life-threatening; hospitalization or prolonged hospitalization indicated; disabling; limited self care ADL. Grade 4 Life-threatening consequences; urgent interventions indicated.

12. Phase 3: Objective Response Rate (ORR) [Up to 12 weeks after first dose of study treatment]

13. Phase 3: Progression Free Survival (PFS) [From first dose of study treatment until the end of study, up to 30 months]

14. Phase 3: Duration of Response (DOR) [From first dose of study treatment up to 12 weeks]

15. Phase 3: Percentage of Participants Who Experienced Successful Mobilization [From baseline until the end of study, up to 30 months]

16. Phase 3: Percentage of Participants Who Had Allogeneic or Autologous Post-baseline Hematopoietic Stem Cell Transplant (HSCT) [From baseline HSCT until the end of study, up to 30 months]

17. Phase 3: Percentage of Participants Who Died Within 100 Days After Hematopoietic Stem Cell Transplantation (HSCT) That Was Not Due to Relapse [100 days after HSCT]

18. Phase 3: Change From Baseline in Patient Reported Clinical Outcome Assessments Quality of Life (QOLCOA) Scores [Up to 30 days after last dose after study treatment]

19. Phase 3: Number of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE) [From first dose of study treatment until 30 days after last dose]

20. Phase 3: Serum Blinatumomab Steady State Concentration (Css) [24 hours after first dose of blinatumomab]

21. Phase 3: Blinatumomab Clearance (CL) [Pre-dose on Day 1, and Days 2, 9 and 16 of Cycle 1 (Cycle 1 was 70 days)]

22. Phase 3: Half-life of Blinatumomab [Pre-dose on Day 1, and Days 2, 9 and 16 of Cycle 1 (Cycle 1 was 70 days)]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Biopsy proven aggressive B-cell Non-Hodgkin Lymphoma (B-NHL), including diffuse large B-cell lymphoma (DLBCL) not otherwise specified (NOS), follicular lymphoma Grade 3B, PMBCL, T-cell rich B-cell lymphoma, or DLBCL that represents transformation of indolent non-Hodgkin's Lymphoma (NHL), (including follicular, marginal zone, and lymphoplasmacytoid lymphoma) excluding chronic lymphocytic leukemia or Hodgkin

Lymphoma. The following histologies are not eligible:

• Lymphoblastic lymphoma

• Burkitt lymphoma

• Mantle cell lymphoma Any histologies not specifically mentioned must be discussed with medical monitor.

• Refractory (no prior CR/CMR) or relapsed (prior CMR) following front line treatment of standard multiagent chemotherapy containing an anthracycline AND an approved anti-CD20 agent. For subjects with refractory disease and who have received radiotherapy, PET positivity should be demonstrated no less than 6 weeks after the last dose of radiotherapy

• Biopsy proven confirmation of relapsed disease.

• Received a minimum of 2 cycles of standard of care platinum-based chemotherapy in the S1 setting and had a response of progressive metabolic disease (PMD), no metabolic response (NMR), partial metabolic response (PMR) as centrally assessed by PET-/ CT scan or received at least 1 cycle of S1 chemotherapy and had evidence of PMD as centrally assessed. A pre-salvage scan is required to be submitted to the central reader if a subject had only 1 cycle of pre-salvage chemotherapy.

• Radiographically measurable disease with a demarcated nodal lesion at least 1.5 cm in its largest dimension or a target extranodal lesion at least 1.0 cm in its largest dimension

• Eastern Cooperative Oncology Group performance status less than or equal to 2

• Intention to proceed to high dose chemotherapy (HDT) and autologous hematopoietic stem cell transplant (HSCT)

• Laboratory parameters:

Hematology:

• Absolute neutrophil count (ANC) ≥ 1.0 x 10^9/L

• Platelets ≥ 75 x 10^9/L

Chemistry:

• Creatinine clearance ≥ 50 mL/min

• Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) < 3X upper limit of normal (ULN)

• Total bilirubin (TBL) < 2x ULN (unless Gilbert's disease or if liver involvement with lymphoma)

Exclusion Criteria:

• CMR following S1 chemotherapy

• Treatment within 30 days prior to randomization with another investigational device or drug study (ies).

• Prior anti-CD19-directed therapies

• Prior HDT with autologous HSCT

• Prior allogeneic HSCT

• Clinically relevant central nervous system (CNS) pathology such as epilepsy, paresis, aphasia, stroke, severe brain injury, dementia, Parkinson's disease, cerebellar disease, organic brain syndrome, or psychosis

• Evidence of CNS involvement by NHL

• Known 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 B-NHL within the past 3 years with the exception of:

• Malignancy treated with curative intent and with no known active disease present for ≥ 3 years before enrollment

• Adequately treated non-melanoma skin cancer or lentigo maligna

• Adequately treated cervical carcinoma in situ

• Adequately treated breast ductal carcinoma in situ

• Prostatic intraepithelial neoplasia without evidence of prostate cancer

• Adequately treated urothelial papillary non-invasive carcinoma or carcinoma in situ

• Known sensitivity to immunoglobulins or any of the components to be administered during dosing.

• Subject likely to not be available to complete all protocol-required study visits or procedures, and/or to comply with all required procedures.

• History or evidence of any other clinically significant disorder, condition or disease (with the exception of those outlined above) that would pose a risk to subject safety or interfere with the study evaluation, procedures or completion.

• Female subjects who are pregnant or breastfeeding or planning to become pregnant or breastfeed, or of childbearing potential unwilling to use an effective method of contraception while receiving, and for an additional 48 hours after the last dose of blinatumomab.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Research Site	Duarte	California	United States	91010
2	Research Site	Baltimore	Maryland	United States	21201
3	Research Site	Oklahoma City	Oklahoma	United States	73104
4	Research Site	Greenville	South Carolina	United States	29607
5	Research Site	St Leonards	New South Wales	Australia	2065
6	Research Site	Herston	Queensland	Australia	4029
7	Research Site	Melbourne	Victoria	Australia	3004
8	Research Site	Parkville	Victoria	Australia	3052
9	Research Site	Murdoch	Western Australia	Australia	6150
10	Research Site	Bruxelles		Belgium	1200
11	Research Site	Gent		Belgium	9000
12	Research Site	Leuven		Belgium	3000
13	Research Site	Montreal	Quebec	Canada	H1T 2M4
14	Research Site	Bergamo		Italy	24127
15	Research Site	Firenze		Italy	50134
16	Research Site	Genova		Italy	16132
17	Research Site	Palermo		Italy	90146
18	Research Site	Pisa		Italy	56100
19	Research Site	Roma		Italy	00161
20	Research Site	Udine		Italy	33100
21	Research Site	San Juan		Puerto Rico	00918
22	Research Site	Cordoba	Andalucía	Spain	14004
23	Research Site	Valladolid	Castilla León	Spain	47012
24	Research Site	Barcelona	Cataluña	Spain	08025
25	Research Site	Santiago de Compostela	Galicia	Spain	15706
26	Research Site	Madrid		Spain	28034
27	Research Site	Madrid		Spain	28041
28	Research Site	Murcia		Spain	30008
29	Research Site	Bristol		United Kingdom	BS2 8ED
30	Research Site	Nottingham		United Kingdom	NG5 1PB
31	Research Site	Sheffield		United Kingdom	S10 2JF

Sponsors and Collaborators

• Amgen

Investigators

• Study Director: MD, Amgen

Study Documents (Full-Text)

• Study Protocol - May 7, 2019
• Statistical Analysis Plan - Sep 23, 2019

More Information

Additional Information:

• AmgenTrials clinical trials website

Publications

None provided.

• Responsible Party: Amgen
• ClinicalTrials.gov Identifier: NCT02910063
• Other Study ID Numbers: 20150292; 2016-002044-16
• First Posted: Sep 21, 2016
• Last Update Posted: Jan 13, 2021
• Last Verified: Dec 1, 2020

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Amgen: Relapsed/Refractory Aggressive B-Cell Non Hodgkin Lymphoma; Blinatumomab; Leukemia; Standard of Care; SOC; Cancer; Chemotherapy
• Additional relevant MeSH terms: Lymphoma; Lymphoma, Non-Hodgkin; Lymphoma, B-Cell; Aggression; Blinatumomab

Study Results

Participant Flow

Recruitment Details	Participants were enrolled at 19 research centers in Australia, Belgium, Italy, Spain, the United Kingdom, and the United States from 23 January 2017 to 15 January 2018.
Pre-assignment Detail	Phase 3 part of the study was not initiated after Phase 2 data was reviewed. No participants were screened or enrolled for Phase 3.

Arm/Group Title	Phase 2: Blinatumomab	Phase 3: Blinatumomab	Phase 3: Investigator's Choice (IC) Chemotherapy
Arm/Group Description	Participants entered a single 70-day dose step cycle, and received a total of 56 days of blinatumomab continuous infusion which was administered as 7 days at 9 microgram (μg)/day, 7 days at 28 μg/day, and 42 days at 112 μg/day, followed by a treatment-free period of 14 days. Eligible participants could then enter an optional Cycle 2, 2 to 4 weeks after the end of the previous cycle. The optional Cycle 2 consisted of a 28-day cycle of blinatumomab continuous infusion administered as 7 days at 9 μg/day, 7 days at 28 μg/day, and 14 days at 112 μg/day.	Participants were to enter a single 70-day dose step cycle, and received a total of 56 days of blinatumomab continuous infusion which was administered as 7 days at 9 microgram (μg)/day, 7 days at 28 μg/day, and 42 days at 112 μg/day, followed by a treatment-free period of 14 days. In March 2019, the decision made to not proceed with Phase 3 and no participants were enrolled. No data is available for Phase 3.	Participants were to receive standard of care (SOC) chemotherapy per investigator´s choice. In March 2019, the decision was made to not proceed with Phase 3 and no participants were enrolled. No data is available for Phase 3.
Period Title: Phase 2
STARTED	41	0	0
Started Cycle 1	41	0	0
Started Optional Cycle 2	4	0	0
COMPLETED	13	0	0
NOT COMPLETED	28	0	0
Period Title: Phase 2
STARTED	0	0	0
COMPLETED	0	0	0
NOT COMPLETED	0	0	0

Baseline Characteristics

Arm/Group Title	Phase 2: Blinatumomab
Arm/Group Description	Participants entered a single 70-day dose step cycle, and received a total of 56 days of blinatumomab continuous infusion which was administered as 7 days at 9 microgram (μg)/day, 7 days at 28 μg/day, and 42 days at 112 μg/day, followed by a treatment-free period of 14 days. Eligible participants could then enter an optional Cycle 2, 2 to 4 weeks after the end of the previous cycle. The optional Cycle 2 consisted of a 28-day cycle of blinatumomab continuous infusion administered as 7 days at 9 μg/day, 7 days at 28 μg/day, and 14 days at 112 μg/day.
Overall Participants	41
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	54.7 (12.4)
Sex: Female, Male (Count of Participants)
Female	13 31.7%
Male	28 68.3%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	6 14.6%
Not Hispanic or Latino	35 85.4%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	1 2.4%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	1 2.4%
White	38 92.7%
More than one race	0 0%
Unknown or Not Reported	1 2.4%

Outcome Measures

1. Primary Outcome

Title	Phase 2: Percentage of Participants Who Achieved Complete Metabolic Response (CMR)
Description	Complete metabolic response (CMR) was determined by central radiographic assessment of positron emission tomography and computed tomography (PET/CT) scans using the Lugano Classification.
Time Frame	Up to 12 weeks after first dose of blinatumomab

Outcome Measure Data

Analysis Population Description

FAS: All participants who received blinatumomab.

Arm/Group Title	Phase 2: Blinatumomab
Arm/Group Description	Participants entered a single 70-day dose step cycle, and received a total of 56 days of blinatumomab continuous infusion which was administered as 7 days at 9 microgram (μg)/day, 7 days at 28 μg/day, and 42 days at 112 μg/day, followed by a treatment-free period of 14 days. Eligible participants could then enter an optional Cycle 2, 2 to 4 weeks after the end of the previous cycle. The optional Cycle 2 consisted of a 28-day cycle of blinatumomab continuous infusion administered as 7 days at 9 μg/day, 7 days at 28 μg/day, and 14 days at 112 μg/day.
Measure Participants	41
Number (95% Confidence Interval) [Percentage of participants]	22.0 53.7%

2. Primary Outcome

Title	Phase 3: Number of Participants Who Achieved Complete Metabolic Response (CMR)
Description	Complete metabolic response (CMR) was determined by central radiographic assessment of positron emission tomography and computed tomography (PET/CT) scans using the Lugano Classification.
Time Frame	Up to 12 weeks after first dose of study treatment

Outcome Measure Data

Analysis Population Description

No data is available for Phase 3. In March 2019, the decision was made to not proceed with Phase 3 and no participants were enrolled.

Arm/Group Title	Phase 3: Blinatumomab	Phase 3: Investigator's Choice (IC) Chemotherapy
Arm/Group Description	Participants were to enter a single 70-day dose step cycle, and received a total of 56 days of blinatumomab continuous infusion which was administered as 7 days at 9 microgram (μg)/day, 7 days at 28 μg/day, and 42 days at 112 μg/day, followed by a treatment-free period of 14 days. In March 2019, the decision made to not proceed with Phase 3 and no participants were enrolled. No data is available for Phase 3.	Participants were to receive standard of care (SOC) chemotherapy per investigator´s choice. In March 2019, the decision was made to not proceed with Phase 3 and no participants were enrolled. No data is available for Phase 3.
Measure Participants	0	0

3. Secondary Outcome

Title	Phase 2: Overall Survival (OS)
Description	OS was defined as the time from the date of randomization until death due to any cause. OS was calculated using Kaplan-Meier estimates.
Time Frame	From randomization until the end of study, up to 30 months

Outcome Measure Data

Analysis Population Description

No data is available for Phase 3. In March 2019, the decision made to not proceed with Phase 3 and no participants were enrolled.

Arm/Group Title	Phase 2: Blinatumomab
Arm/Group Description	Participants entered a single 70-day dose step cycle, and received a total of 56 days of blinatumomab continuous infusion which was administered as 7 days at 9 microgram (μg)/day, 7 days at 28 μg/day, and 42 days at 112 μg/day, followed by a treatment-free period of 14 days. Eligible participants could then enter an optional Cycle 2, 2 to 4 weeks after the end of the previous cycle. The optional Cycle 2 consisted of a 28-day cycle of blinatumomab continuous infusion administered as 7 days at 9 μg/day, 7 days at 28 μg/day, and 14 days at 112 μg/day.
Measure Participants	41
Median (95% Confidence Interval) [Months]	11.2

4. Secondary Outcome

Title	Phase 2: Objective Response Rate (ORR)
Description	ORR is inclusive of all participants who achieved CMR or those who achieved partial metabolic response (PMR), as determined by central radiographic assessment of PET/CT scans using the Lugano Classification.
Time Frame	Up to 12 weeks after first dose of blinatumomab

Outcome Measure Data

Analysis Population Description

FAS: All participants who received blinatumomab.

Arm/Group Title	Phase 2: Blinatumomab
Arm/Group Description	Participants entered a single 70-day dose step cycle, and received a total of 56 days of blinatumomab continuous infusion which was administered as 7 days at 9 microgram (μg)/day, 7 days at 28 μg/day, and 42 days at 112 μg/day, followed by a treatment-free period of 14 days. Eligible participants could then enter an optional Cycle 2, 2 to 4 weeks after the end of the previous cycle. The optional Cycle 2 consisted of a 28-day cycle of blinatumomab continuous infusion administered as 7 days at 9 μg/day, 7 days at 28 μg/day, and 14 days at 112 μg/day.
Measure Participants	41
Number (95% Confidence Interval) [Percentage of participants]	36.6 89.3%

5. Secondary Outcome

Title	Phase 2: Progression Free Survival (PFS)
Description	PFS was defined as the time from start of treatment with blinatumomab until the date of diagnosis of progression of lymphoma, or date of death, whichever is earliest. PFS was estimated using Kaplan-Meier method.
Time Frame	From first dose of blinatumomab until the end of study, up to 30 months

Outcome Measure Data

Analysis Population Description

FAS: All participants who received blinatumomab.

Arm/Group Title	Phase 2: Blinatumomab
Arm/Group Description	Participants entered a single 70-day dose step cycle, and received a total of 56 days of blinatumomab continuous infusion which was administered as 7 days at 9 microgram (μg)/day, 7 days at 28 μg/day, and 42 days at 112 μg/day, followed by a treatment-free period of 14 days. Eligible participants could then enter an optional Cycle 2, 2 to 4 weeks after the end of the previous cycle. The optional Cycle 2 consisted of a 28-day cycle of blinatumomab continuous infusion administered as 7 days at 9 μg/day, 7 days at 28 μg/day, and 14 days at 112 μg/day.
Measure Participants	41
Median (95% Confidence Interval) [Months]	2.9

6. Secondary Outcome

Title	Phase 2: Duration of Response (DOR)
Description	DOR was calculated only for participants who achieve a response (CMR or PMR). The duration was calculated from the date a response, CMR or PMR, was first achieved until the earliest date of a disease assessment indicating disease progression or death, whichever occured first. DOR was estimated using Kaplan-Meier method.
Time Frame	From first dose of blinatumomab up to 12 weeks

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS): All participants who received blinatumomab.

Arm/Group Title	Phase 2: Blinatumomab
Arm/Group Description	Participants entered a single 70-day dose step cycle, and received a total of 56 days of blinatumomab continuous infusion which was administered as 7 days at 9 microgram (μg)/day, 7 days at 28 μg/day, and 42 days at 112 μg/day, followed by a treatment-free period of 14 days. Eligible participants could then enter an optional Cycle 2, 2 to 4 weeks after the end of the previous cycle. The optional Cycle 2 consisted of a 28-day cycle of blinatumomab continuous infusion administered as 7 days at 9 μg/day, 7 days at 28 μg/day, and 14 days at 112 μg/day.
Measure Participants	41
Median (95% Confidence Interval) [Months]	6.1

7. Secondary Outcome

Title	Phase 2: Percentage of Participants Who Experienced Successful Mobilization
Description	Successful mobilization rate was defined as the percentage of participants who initiated mobilization while in remission and without any other anti-tumor therapy where the mobilization procedure had an outcome of 'Successful'. Successful mobilization was dictated by institutional standards and defined when the target cell dose was no less than 2 x 10^6 CD34+ cells/kg.
Time Frame	From first dose of blinatumomab until the end of study, up to 30 months

Outcome Measure Data

Analysis Population Description

Responder Analysis Set: All participants who had a CMR or PMR per central review during the first 12 weeks after initiation of blinatumomab.

Arm/Group Title	Phase 2: Blinatumomab
Arm/Group Description	Participants entered a single 70-day dose step cycle, and received a total of 56 days of blinatumomab continuous infusion which was administered as 7 days at 9 microgram (μg)/day, 7 days at 28 μg/day, and 42 days at 112 μg/day, followed by a treatment-free period of 14 days. Eligible participants could then enter an optional Cycle 2, 2 to 4 weeks after the end of the previous cycle. The optional Cycle 2 consisted of a 28-day cycle of blinatumomab continuous infusion administered as 7 days at 9 μg/day, 7 days at 28 μg/day, and 14 days at 112 μg/day.
Measure Participants	15
Number (95% Confidence Interval) [Percentage of participants]	40.0 97.6%

8. Secondary Outcome

Title	Phase 2: Percentage of Participants Who Had Allogeneic or Autologous Post-baseline Hematopoietic Stem Cell Transplant (HSCT)
Description	The percentage of responders per investigator's review (participants who achieved either CMR or PMR during the treatment) who have undergone allogeneic (allo) HSCT or autologous (auto) HSCT while in remission and without any other anti-cancer treatment.
Time Frame	From baseline HSCT until the end of study, up to 30 months

Outcome Measure Data

Analysis Population Description

FAS: All participants who received blinatumomab.

Arm/Group Title	Phase 2: Blinatumomab
Arm/Group Description	Participants entered a single 70-day dose step cycle, and received a total of 56 days of blinatumomab continuous infusion which was administered as 7 days at 9 microgram (μg)/day, 7 days at 28 μg/day, and 42 days at 112 μg/day, followed by a treatment-free period of 14 days. Eligible participants could then enter an optional Cycle 2, 2 to 4 weeks after the end of the previous cycle. The optional Cycle 2 consisted of a 28-day cycle of blinatumomab continuous infusion administered as 7 days at 9 μg/day, 7 days at 28 μg/day, and 14 days at 112 μg/day.
Measure Participants	41
AlloHSCT	6.7 16.3%
AutoHSCT	53.3 130%

9. Secondary Outcome

Title	Phase 2: Cumulative Incidence Function Estimate of 100-day Mortality After HSCT Presented as Percentage of Participants That Died Not Due to Relapse, With Relapse and Death Due to Relapse as Competing Events
Description	Non-relapse mortality rate at 100 days after HSCT was calculated as the percentage of participants who died not due to relapse. Only participants who achieved a response per investigator's review and underwent autoHSCT are included.
Time Frame	100 days after HSCT

Outcome Measure Data

Analysis Population Description

AutoHSCT Analysis Set: All participants who achieved a response and underwent autoHSCT while in remission and without any other anti-cancer treatment.

Arm/Group Title	Phase 2: Blinatumomab
Arm/Group Description	Participants entered a single 70-day dose step cycle, and received a total of 56 days of blinatumomab continuous infusion which was administered as 7 days at 9 microgram (μg)/day, 7 days at 28 μg/day, and 42 days at 112 μg/day, followed by a treatment-free period of 14 days. Eligible participants could then enter an optional Cycle 2, 2 to 4 weeks after the end of the previous cycle. The optional Cycle 2 consisted of a 28-day cycle of blinatumomab continuous infusion administered as 7 days at 9 μg/day, 7 days at 28 μg/day, and 14 days at 112 μg/day.
Measure Participants	9
Number (95% Confidence Interval) [Percentage of participants]	0.0 0%

10. Secondary Outcome

Title	Phase 2: Blinatumomab Steady State Concentrations (Css)
Description	Pharmacokinetic (PK) parameters were estimated by non compartmental analysis. The Css of blinatumomab was summarized as the observed concentrations collected after at least 24 hours after the start of continuous IV infusion or start of dose step, where appropriate.
Time Frame	Pre-dose on Day 1, and post-dose on Days 2, 9 and 16 of Cycle 1 (Cycle 1 was 70 days)

Outcome Measure Data

Analysis Population Description

PK analysis Set: All subjects who received blinatumomab at each individual dose and had at least one PK sample collected.

Arm/Group Title	Phase 2: Blinatumomab 9 µg/Day	Phase 2: Blinatumomab 28 µg/Day	Phase 2: Blinatumomab 112 µg/Day
Arm/Group Description	All participants who received blinatumomab 9 µg/day continuous infusion which was administered for 7 days of in Week 1 of Cycle 1 (Cycle 1 was 70 days in length).	All participants who received blinatumomab 28 µg/day continuous infusion which was administered for 7 days in Week 2 of Cycle 1 (Cycle 1 was 70 days in length).	All participants who received blinatumomab 112 µg/day continuous infusion which was administered for 7 days in Week 3 of Cycle 1 (Cycle 1 was 70 days in length).
Measure Participants	41	38	32
Mean (Standard Deviation) [Picograms/millilter (pg/mL)]	249 (200)	804 (513)	3470 (3700)

11. Secondary Outcome

Title	Phase 2: Blinatumomab Clearance (CL)
Description	Serum blinatumomab CL was calculated as CL=R0/Css,DN; where R0 is the infusion rate (μg/hr) and Css,DN is the dose normalized average Css. For the CL calculation, the Css,DN was normalized to the 112 μg/day dose in which the value of dose in units of μg/hr was used for the infusion rate.
Time Frame	Pre-dose on Day 1, and post-dose on Days 2, 9 and 16 of Cycle 1 (Cycle 1 was 70 days)

Outcome Measure Data

Analysis Population Description

PK analysis Set: All subjects who received any infusion of blinatumomab and had at least one PK sample collected.

Arm/Group Title	Phase 2: Blinatumomab
Arm/Group Description	Participants entered a single 70-day dose step cycle, and received a total of 56 days of blinatumomab continuous infusion which was administered as 7 days at 9 microgram (μg)/day, 7 days at 28 μg/day, and 42 days at 112 μg/day, followed by a treatment-free period of 14 days. Eligible participants could then enter an optional Cycle 2, 2 to 4 weeks after the end of the previous cycle. The optional Cycle 2 consisted of a 28-day cycle of blinatumomab continuous infusion administered as 7 days at 9 μg/day, 7 days at 28 μg/day, and 14 days at 112 μg/day.
Measure Participants	41
Mean (Standard Deviation) [Liter/hour (L/hr)]	1.78 (0.747)

12. Secondary Outcome

Title	Phase 2: Half-life of Blinatumomab
Time Frame	Pre-dose on Day 1, and Days 2, 9 and 16 of Cycle 1 (Cycle 1 was 70 days)

Outcome Measure Data

Analysis Population Description

Blinatumomab half-life was not reported as the serum blinatumomab concentration data collected for PK assessments did not support its estimation. This is in adherence with the considerations for reporting of PK assessments as detailed in Protocol Section 10.6.

Arm/Group Title	Phase 2: Blinatumomab
Arm/Group Description	Participants entered a single 70-day dose step cycle, and received a total of 56 days of blinatumomab continuous infusion which was administered as 7 days at 9 microgram (μg)/day, 7 days at 28 μg/day, and 42 days at 112 μg/day, followed by a treatment-free period of 14 days. Eligible participants could then enter an optional Cycle 2, 2 to 4 weeks after the end of the previous cycle. The optional Cycle 2 consisted of a 28-day cycle of blinatumomab continuous infusion administered as 7 days at 9 μg/day, 7 days at 28 μg/day, and 14 days at 112 μg/day.
Measure Participants	0

13. Secondary Outcome

Title	Phase 2: Number of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE)
Description	Treatment-emergent adverse events were events with an onset after the administration of the first dose of blinatumomab. TEAEs were graded using the Common Terminology Criteria for Adverse Events (CTCAE). Grade 2 Moderate; minimal, local or noninvasive intervention indicated; limited age appropriate instrumental activities of daily life (ADL). Grade 3 Severe or medically significant but not immediately life-threatening; hospitalization or prolonged hospitalization indicated; disabling; limited self care ADL. Grade 4 Life-threatening consequences; urgent interventions indicated.
Time Frame	From first dose of blinatumomab until 30 days after last dose. The maximum treatment duration for blinatumomab was 114 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Phase 2: Blinatumomab
Arm/Group Description	Participants entered a single 70-day dose step cycle, and received a total of 56 days of blinatumomab continuous infusion which was administered as 7 days at 9 microgram (μg)/day, 7 days at 28 μg/day, and 42 days at 112 μg/day, followed by a treatment-free period of 14 days. Eligible participants could then enter an optional Cycle 2, 2 to 4 weeks after the end of the previous cycle. The optional Cycle 2 consisted of a 28-day cycle of blinatumomab continuous infusion administered as 7 days at 9 μg/day, 7 days at 28 μg/day, and 14 days at 112 μg/day.
Measure Participants	41
TEAEs	41 100%
Grade ≥ 2 TEAEs	37 90.2%
Grade ≥ 3 TEAEs	29 70.7%
Grade ≥ 4 TEAEs	12 29.3%
Serious TEAEs	20 48.8%
TEAEs leading to discontinuation of blinatumomab	7 17.1%
TEAEs leading to interruption of blinatumomab	13 31.7%
Fatal TEAEs	7 17.1%

14. Secondary Outcome

Title	Phase 3: Objective Response Rate (ORR)
Time Frame	Up to 12 weeks after first dose of study treatment

Outcome Measure Data

Analysis Population Description

No data is available for Phase 3. In March 2019, the decision made to not proceed with Phase 3 and no participants were enrolled.

Arm/Group Title	Phase 3: Blinatumomab	Phase 3: Investigator's Choice (IC) Chemotherapy
Arm/Group Description	Participants were to enter a single 70-day dose step cycle, and received a total of 56 days of blinatumomab continuous infusion which was administered as 7 days at 9 microgram (μg)/day, 7 days at 28 μg/day, and 42 days at 112 μg/day, followed by a treatment-free period of 14 days. In March 2019, the decision made to not proceed with Phase 3 and no participants were enrolled. No data is available for Phase 3.	Participants were to receive standard of care (SOC) chemotherapy per investigator´s choice. In March 2019, the decision was made to not proceed with Phase 3 and no participants were enrolled. No data is available for Phase 3.
Measure Participants	0	0

15. Secondary Outcome

Title	Phase 3: Progression Free Survival (PFS)
Time Frame	From first dose of study treatment until the end of study, up to 30 months

Outcome Measure Data

Analysis Population Description

No data is available for Phase 3. In March 2019, the decision made to not proceed with Phase 3 and no participants were enrolled.

Arm/Group Title	Phase 3: Blinatumomab	Phase 3: Investigator's Choice (IC) Chemotherapy
Arm/Group Description	Participants were to enter a single 70-day dose step cycle, and received a total of 56 days of blinatumomab continuous infusion which was administered as 7 days at 9 microgram (μg)/day, 7 days at 28 μg/day, and 42 days at 112 μg/day, followed by a treatment-free period of 14 days. In March 2019, the decision made to not proceed with Phase 3 and no participants were enrolled. No data is available for Phase 3.	Participants were to receive standard of care (SOC) chemotherapy per investigator´s choice. In March 2019, the decision was made to not proceed with Phase 3 and no participants were enrolled. No data is available for Phase 3.
Measure Participants	0	0

16. Secondary Outcome

Title	Phase 3: Duration of Response (DOR)
Time Frame	From first dose of study treatment up to 12 weeks

Outcome Measure Data

Analysis Population Description

No data is available for Phase 3. In March 2019, the decision made to not proceed with Phase 3 and no participants were enrolled.

Arm/Group Title	Phase 3: Blinatumomab	Phase 3: Investigator's Choice (IC) Chemotherapy
Arm/Group Description	Participants were to enter a single 70-day dose step cycle, and received a total of 56 days of blinatumomab continuous infusion which was administered as 7 days at 9 microgram (μg)/day, 7 days at 28 μg/day, and 42 days at 112 μg/day, followed by a treatment-free period of 14 days. In March 2019, the decision made to not proceed with Phase 3 and no participants were enrolled. No data is available for Phase 3.	Participants were to receive standard of care (SOC) chemotherapy per investigator´s choice. In March 2019, the decision was made to not proceed with Phase 3 and no participants were enrolled. No data is available for Phase 3.
Measure Participants	0	0

17. Secondary Outcome

Title	Phase 3: Percentage of Participants Who Experienced Successful Mobilization
Time Frame	From baseline until the end of study, up to 30 months

Outcome Measure Data

Analysis Population Description

No data is available for Phase 3. In March 2019, the decision made to not proceed with Phase 3 and no participants were enrolled.

Arm/Group Title	Phase 3: Blinatumomab	Phase 3: Investigator's Choice (IC) Chemotherapy
Arm/Group Description	Participants were to enter a single 70-day dose step cycle, and received a total of 56 days of blinatumomab continuous infusion which was administered as 7 days at 9 microgram (μg)/day, 7 days at 28 μg/day, and 42 days at 112 μg/day, followed by a treatment-free period of 14 days. In March 2019, the decision made to not proceed with Phase 3 and no participants were enrolled. No data is available for Phase 3.	Participants were to receive standard of care (SOC) chemotherapy per investigator´s choice. In March 2019, the decision was made to not proceed with Phase 3 and no participants were enrolled. No data is available for Phase 3.
Measure Participants	0	0

18. Secondary Outcome

Title	Phase 3: Percentage of Participants Who Had Allogeneic or Autologous Post-baseline Hematopoietic Stem Cell Transplant (HSCT)
Time Frame	From baseline HSCT until the end of study, up to 30 months

Outcome Measure Data

Analysis Population Description

No data is available for Phase 3. In March 2019, the decision made to not proceed with Phase 3 and no participants were enrolled.

Arm/Group Title	Phase 3: Blinatumomab	Phase 3: Investigator's Choice (IC) Chemotherapy
Arm/Group Description	Participants were to enter a single 70-day dose step cycle, and received a total of 56 days of blinatumomab continuous infusion which was administered as 7 days at 9 microgram (μg)/day, 7 days at 28 μg/day, and 42 days at 112 μg/day, followed by a treatment-free period of 14 days. In March 2019, the decision made to not proceed with Phase 3 and no participants were enrolled. No data is available for Phase 3.	Participants were to receive standard of care (SOC) chemotherapy per investigator´s choice. In March 2019, the decision was made to not proceed with Phase 3 and no participants were enrolled. No data is available for Phase 3.
Measure Participants	0	0

19. Secondary Outcome

Title	Phase 3: Percentage of Participants Who Died Within 100 Days After Hematopoietic Stem Cell Transplantation (HSCT) That Was Not Due to Relapse
Time Frame	100 days after HSCT

Outcome Measure Data

Analysis Population Description

No data is available for Phase 3. In March 2019, the decision made to not proceed with Phase 3 and no participants were enrolled.

Arm/Group Title	Phase 3: Blinatumomab	Phase 3: Investigator's Choice (IC) Chemotherapy
Arm/Group Description	Participants were to enter a single 70-day dose step cycle, and received a total of 56 days of blinatumomab continuous infusion which was administered as 7 days at 9 microgram (μg)/day, 7 days at 28 μg/day, and 42 days at 112 μg/day, followed by a treatment-free period of 14 days. In March 2019, the decision made to not proceed with Phase 3 and no participants were enrolled. No data is available for Phase 3.	Participants were to receive standard of care (SOC) chemotherapy per investigator´s choice. In March 2019, the decision was made to not proceed with Phase 3 and no participants were enrolled. No data is available for Phase 3.
Measure Participants	0	0

20. Secondary Outcome

Title	Phase 3: Change From Baseline in Patient Reported Clinical Outcome Assessments Quality of Life (QOLCOA) Scores
Time Frame	Up to 30 days after last dose after study treatment

Outcome Measure Data

Analysis Population Description

No data is available for Phase 3. In March 2019, the decision made to not proceed with Phase 3 and no participants were enrolled.

Arm/Group Title	Phase 3: Blinatumomab	Phase 3: Investigator's Choice (IC) Chemotherapy
Arm/Group Description	Participants were to enter a single 70-day dose step cycle, and received a total of 56 days of blinatumomab continuous infusion which was administered as 7 days at 9 microgram (μg)/day, 7 days at 28 μg/day, and 42 days at 112 μg/day, followed by a treatment-free period of 14 days. In March 2019, the decision made to not proceed with Phase 3 and no participants were enrolled. No data is available for Phase 3.	Participants were to receive standard of care (SOC) chemotherapy per investigator´s choice. In March 2019, the decision was made to not proceed with Phase 3 and no participants were enrolled. No data is available for Phase 3.
Measure Participants	0	0

21. Secondary Outcome

Title	Phase 3: Number of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE)
Time Frame	From first dose of study treatment until 30 days after last dose

Outcome Measure Data

Analysis Population Description

No data is available for Phase 3. In March 2019, the decision made to not proceed with Phase 3 and no participants were enrolled.

Arm/Group Title	Phase 3: Blinatumomab	Phase 3: Investigator's Choice (IC) Chemotherapy
Arm/Group Description	Participants were to enter a single 70-day dose step cycle, and received a total of 56 days of blinatumomab continuous infusion which was administered as 7 days at 9 microgram (μg)/day, 7 days at 28 μg/day, and 42 days at 112 μg/day, followed by a treatment-free period of 14 days. In March 2019, the decision made to not proceed with Phase 3 and no participants were enrolled. No data is available for Phase 3.	Participants were to receive standard of care (SOC) chemotherapy per investigator´s choice. In March 2019, the decision was made to not proceed with Phase 3 and no participants were enrolled. No data is available for Phase 3.
Measure Participants	0	0

22. Secondary Outcome

Title	Phase 3: Serum Blinatumomab Steady State Concentration (Css)
Time Frame	24 hours after first dose of blinatumomab

Outcome Measure Data

Analysis Population Description

No data is available for Phase 3. In March 2019, the decision made to not proceed with Phase 3 and no participants were enrolled.

Arm/Group Title	Phase 3: Blinatumomab	Phase 3: Investigator's Choice (IC) Chemotherapy
Arm/Group Description	Participants were to enter a single 70-day dose step cycle, and received a total of 56 days of blinatumomab continuous infusion which was administered as 7 days at 9 microgram (μg)/day, 7 days at 28 μg/day, and 42 days at 112 μg/day, followed by a treatment-free period of 14 days. In March 2019, the decision made to not proceed with Phase 3 and no participants were enrolled. No data is available for Phase 3.	Participants were to receive standard of care (SOC) chemotherapy per investigator´s choice. In March 2019, the decision was made to not proceed with Phase 3 and no participants were enrolled. No data is available for Phase 3.
Measure Participants	0	0

23. Secondary Outcome

Title	Phase 3: Blinatumomab Clearance (CL)
Time Frame	Pre-dose on Day 1, and Days 2, 9 and 16 of Cycle 1 (Cycle 1 was 70 days)

Outcome Measure Data

Analysis Population Description

No data is available for Phase 3. In March 2019, the decision made to not proceed with Phase 3 and no participants were enrolled.

Arm/Group Title	Phase 3: Blinatumomab	Phase 3: Investigator's Choice (IC) Chemotherapy
Arm/Group Description	Participants were to enter a single 70-day dose step cycle, and received a total of 56 days of blinatumomab continuous infusion which was administered as 7 days at 9 microgram (μg)/day, 7 days at 28 μg/day, and 42 days at 112 μg/day, followed by a treatment-free period of 14 days. In March 2019, the decision made to not proceed with Phase 3 and no participants were enrolled. No data is available for Phase 3.	Participants were to receive standard of care (SOC) chemotherapy per investigator´s choice. In March 2019, the decision was made to not proceed with Phase 3 and no participants were enrolled. No data is available for Phase 3.
Measure Participants	0	0

24. Secondary Outcome

Title	Phase 3: Half-life of Blinatumomab
Time Frame	Pre-dose on Day 1, and Days 2, 9 and 16 of Cycle 1 (Cycle 1 was 70 days)

Outcome Measure Data

Analysis Population Description

No data is available for Phase 3. In March 2019, the decision made to not proceed with Phase 3 and no participants were enrolled.

Arm/Group Title	Phase 3: Blinatumomab	Phase 3: Investigator's Choice (IC) Chemotherapy
Arm/Group Description	Participants were to enter a single 70-day dose step cycle, and received a total of 56 days of blinatumomab continuous infusion which was administered as 7 days at 9 microgram (μg)/day, 7 days at 28 μg/day, and 42 days at 112 μg/day, followed by a treatment-free period of 14 days. In March 2019, the decision made to not proceed with Phase 3 and no participants were enrolled. No data is available for Phase 3.	Participants were to receive standard of care (SOC) chemotherapy per investigator´s choice. In March 2019, the decision was made to not proceed with Phase 3 and no participants were enrolled. No data is available for Phase 3.
Measure Participants	0	0

Adverse Events

Time Frame	From first dose of blinatumomab until 30 days after last dose. The maximum treatment duration for blinatumomab was 114 days
Adverse Event Reporting Description	All-cause mortality, serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. No data is available for Phase 3. In March 2019, decision made to not proceed with Phase 3 and no participants were enrolled. The data below is only inclusive of participants in Phase 2.
Arm/Group Title	Phase 2: Blinatumomab
Arm/Group Description	Participants entered a single 70-day dose step cycle, and received a total of 56 days of blinatumomab continuous infusion which was administered as 7 days at 9 microgram (μg)/day, 7 days at 28 μg/day, and 42 days at 112 μg/day, followed by a treatment-free period of 14 days. Eligible participants could then enter an optional Cycle 2, 2 to 4 weeks after the end of the previous cycle. The optional Cycle 2 consisted of a 28-day cycle of blinatumomab continuous infusion administered as 7 days at 9 μg/day, 7 days at 28 μg/day, and 14 days at 112 μg/day.
All Cause Mortality
	Phase 2: Blinatumomab
	Affected / at Risk (%)	# Events
Total	25/41 (61%)
Serious Adverse Events
	Phase 2: Blinatumomab
	Affected / at Risk (%)	# Events
Total	20/41 (48.8%)
Cardiac disorders
Atrial fibrillation	1/41 (2.4%)
Gastrointestinal disorders
Abdominal pain	1/41 (2.4%)
Pancreatitis acute	1/41 (2.4%)
General disorders
Pyrexia	1/41 (2.4%)
Infections and infestations
Bacteraemia	1/41 (2.4%)
Lower respiratory tract infection	1/41 (2.4%)
Pneumonia	1/41 (2.4%)
Sepsis	2/41 (4.9%)
Staphylococcal bacteraemia	1/41 (2.4%)
Musculoskeletal and connective tissue disorders
Back pain	1/41 (2.4%)
Pain in extremity	1/41 (2.4%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
B-cell lymphoma	1/41 (2.4%)
Diffuse large B-cell lymphoma	1/41 (2.4%)
Diffuse large B-cell lymphoma refractory	2/41 (4.9%)
Lymphoma	1/41 (2.4%)
Non-Hodgkin's lymphoma	1/41 (2.4%)
Nervous system disorders
Hemiparesis	1/41 (2.4%)
Neurotoxicity	1/41 (2.4%)
Psychiatric disorders
Confusional state	3/41 (7.3%)
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism	1/41 (2.4%)
Vascular disorders
Deep vein thrombosis	1/41 (2.4%)
Orthostatic hypotension	1/41 (2.4%)
Other (Not Including Serious) Adverse Events
	Phase 2: Blinatumomab
	Affected / at Risk (%)	# Events
Total	29/41 (70.7%)
Blood and lymphatic system disorders
Anaemia	6/41 (14.6%)
Neutropenia	5/41 (12.2%)
Gastrointestinal disorders
Abdominal pain	4/41 (9.8%)
Constipation	6/41 (14.6%)
Diarrhoea	4/41 (9.8%)
Nausea	6/41 (14.6%)
Stomatitis	3/41 (7.3%)
General disorders
Asthenia	3/41 (7.3%)
Fatigue	4/41 (9.8%)
Oedema peripheral	8/41 (19.5%)
Pyrexia	9/41 (22%)
Metabolism and nutrition disorders
Hypoalbuminaemia	4/41 (9.8%)
Hypomagnesaemia	5/41 (12.2%)
Musculoskeletal and connective tissue disorders
Arthralgia	4/41 (9.8%)
Back pain	9/41 (22%)
Pain in extremity	4/41 (9.8%)
Nervous system disorders
Aphasia	3/41 (7.3%)
Headache	10/41 (24.4%)
Paraesthesia	3/41 (7.3%)
Tremor	9/41 (22%)
Psychiatric disorders
Confusional state	4/41 (9.8%)
Insomnia	5/41 (12.2%)
Respiratory, thoracic and mediastinal disorders
Cough	3/41 (7.3%)
Vascular disorders
Hypotension	3/41 (7.3%)

Limitations/Caveats

Phase 3 part of the study was not initiated after Phase 2 data was reviewed. No participants were screened or enrolled for Phase 3.

More Information

Certain Agreements

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

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.