Back to results

Phase 3 Trial of Blinatumomab vs Standard Chemotherapy in Pediatric Subjects With HIgh-Risk (HR) First Relapse B-precursor Acute Lymphoblastic Leukemia (ALL)

Primary Purpose

Leukemia, Acute Lymphoblastic

Status

Completed

Phase

Phase 3

Locations

International

Study Type

Interventional

Intervention

Blinatumomab

Dexamethasone

Vincrisitne

Daunorubicin

Methotrexate

Ifosfamide

PEG-asparaginase

Erwinia-asparaginase

About this trial

This is an interventional treatment trial for Leukemia, Acute Lymphoblastic focused on measuring ALL, High-risk first relapse B-precursor ALL, Precursor Cell Lymphoblastic Leukemia, Neoplasms, Lymphoproliferative Disorders, Immunoproliferative Disorders, Antibodies, Bispecific

Eligibility Criteria

0 Years - 17 Years (Child)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Subjects with Philadelphia chromosome negative (Ph-) high-risk (HR) first relapse B-precursor acute lymphoblastic leukemia (ALL; as defined by International Berlin-Frankfurt-Muenster study group/International study for treatment of childhood relapsed ALL [I-BFM SG/IntReALL] criteria)
Subjects with bone marrow blast percentage < 5% (M1) or bone marrow blast percentage < 25% and ≥5% (M2) marrow at the time of randomization,
Age > 28 days and < 18 years at the time of informed consent/assent
Subject's legally acceptable representative has provided informed consent when the subject is legally too young to provide informed consent and the subject has provided written assent based on local regulations and/or guidelines prior to any study-specific activities/procedures being initiated
Availability of the following material from relapse diagnosis for central analysis of minimal residual disease (MRD) by polymerase chain reaction (PCR): clone-specific primers and reference deoxyribonucleic acid (DNA), as well as primer sequences and analyzed sequences of clonal rearrangements (cases with isolated extramedullary relapse or cases with technical and/or logistic hurdles to obtain and process bone marrow material are exempt from providing this material. In these cases, central MRD analysis only by Flow is permitted).

Exclusion Criteria:

Clinically relevant central nervous system (CNS) pathology requiring treatment (eg, unstable epilepsy). Evidence of current CNS (CNS 2, CNS 3) involvement by ALL. Subjects with CNS relapse at the time of relapse are eligible if CNS is successfully treated prior to enrollment
Peripheral neutrophils < 500/μL prior to start of treatment
Peripheral platelets < 50,000/μL prior to start of treatment
Currently receiving treatment in another investigational device or drug study or less than 4 weeks since ending treatment on another investigational device or drug study(s), procedures required by IntReALL high-risk (HR) guidelines are allowed
Chemotherapy related toxicities that have not resolved to ≤ grade 2 (except for parameters defined in Exclusion Criteria 202, 203, 204, and 217)
Symptoms and/or clinical signs and/or radiological and/or sonographic signs that indicate an acute or uncontrolled chronic infection, any other concurrent disease or medical condition that could be exacerbated by the treatment or would seriously complicate compliance with the protocol
Abnormal renal or hepatic function prior to start of treatment (day 1) as defined below
Abnormal serum creatinine based on age/gender
Total bilirubin > 3.0 mg/dL prior to start of treatment (unless related to Gilbert's or Meulengracht disease)
Documented infection with human immunodeficiency virus (HIV)
Known hypersensitivity to immunoglobulins or any of the products or components to be administered during dosing (excluding asparaginase)
Post-menarchal female subject who is pregnant or breastfeeding, or is planning to become pregnant or breastfeed while receiving protocol-specified therapy and for at least 12 months after the last dose of chemotherapy
Post-menarchal female subject who is not willing to practice true sexual abstinence or use a highly effective form of contraception while receiving protocol-specified therapy and for at least 12 months after the last dose of chemotherapy
Sexually mature male subject who is not willing to practice true sexual abstinence or use a condom with spermicide while receiving protocol-specified therapy and for at least 6 months after last dose of chemotherapy. In countries where spermicide is not available, a condom without spermicide is acceptable
Sexually mature male subject who is not willing to abstain from sperm donation while receiving protocol-specified therapy and for at least 6 months after last dose of chemotherapy
Subject likely to not be available to complete all protocol-required study visits or procedures, including follow-up visits, and/or to comply with all required study procedures to the best of the subject's and investigator's knowledge
History or evidence of any other clinically significant disorder, condition or disease (with the exception of those outlined above) that, in the opinion of the investigator or Amgen physician, if consulted, would pose a risk to subject safety or interfere with the study evaluation, procedures, or completion
Placed into an institution due to juridical or regulatory ruling.

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Experimental

Arm Label

High Risk Consolidation 3 (HC3) Chemotherapy

Blinatumomab

Arm Description

One week of treatment with HC3 followed by 3 weeks of no treatment. The standard intensive consolidation chemotherapy course HC3 includes dexamethasone (10 mg/m^2/day intravenous [IV] on Days 1-6), vincrisitne (1.5 mg/m^2/day IV on Days 1 and 6), daunorubicin (30 mg/m^2 IV over 24 hours on Day 5), methotrexate (1 g/m^2 IV over 36 hours on Day 1), ifosfamide (800 mg/m^2 IV for 1 hour on Days 2-4), and pegylated [PEG]-asparaginase (1000 U/m^2 IV for 2 hours or intramuscularly [IM] on Day 6) or, if allergic, erwinia-asparaginase (20,000 units/m^2 IV or IM every 48 hours for a total of 6 doses).

15 μg/m^2/day as a continuous intravenous infusion (CIVI) for 4 weeks

Outcomes

Primary Outcome Measures

Kaplan Meier Estimate: Event-Free Survival (EFS; Primary Analysis)

EFS is calculated from the time of randomization until the date of relapse or M2 marrow (representative bone marrow aspirate or biopsy with ≥ 5% and < 25% blasts) after having achieved a complete remission (CR), failure to achieve a CR at the end of treatment, second malignancy, or death due to any cause, whichever occurs first. Participants who failed to achieve a CR following treatment with investigational product (IP) or who died before the disease assessment at the end of treatment were considered treatment failures and assigned an EFS duration of 1 day. Participants still alive and event-free were censored on their last disease assessment date. Participants were said to be in CR when they had the following: M1 marrow Peripheral blood without blasts Absence of extramedullary leukemic involvement Months are calculated as days from randomization date to event/censor date, divided by 30.5.

Kaplan Meier Estimate: EFS (Final Analysis)

EFS is calculated from the time of randomization until the date of relapse or M2 marrow after having achieved a CR, failure to achieve a CR at the end of treatment, second malignancy, or death due to any cause, whichever occurs first. Participants who failed to achieve a CR following treatment with IP or who died before the disease assessment at the end of treatment were considered treatment failures and assigned an EFS duration of 1 day. Participants still alive and event-free were censored on their last disease assessment date. Participants were said to be in CR when they had the following: M1 marrow Peripheral blood without blasts Absence of extramedullary leukemic involvement Months are calculated as days from randomization date to event/censor date, divided by 30.5.

Secondary Outcome Measures

Kaplan Meier Estimate: Overall Survival (OS)

OS was calculated from time of randomization until death due to any cause. Participants still alive were censored at the date they were last known to be alive. Months were calculated as days from randomization date to event/censor date, divided by 30.5.

Percentage of Participants With an MRD Response Within 29 Days of Treatment Initiation

At the end of the first treatment cycle (Day 29) a bone marrow aspiration/biopsy was performed and evaluated by the central MRD laboratory. MRD response was defined as MRD level < 10^-4, by polymerase chain reaction (PCR) or flow cytometry, at the end of treatment (Cycle 1 Day 29) with study drug. Participants who were part of the MRD Evaluable Set and were missing the end of treatment (Cycle 1 Day 29) assessment for a respective MRD assessment method were considered not to have achieved a response.

Cumulative Incidence of Relapse (CIR)

CIR estimate, presented as median months to relapse, calculated from date of achievement of first CR, using the cumulative incidence method (Fine JP, Gray RJ:1999). Deaths prior to relapse not considered related to an otherwise undocumented relapse were treated as a competing risk. Participants still alive without a date of relapse were censored at the time of last follow-up. Relapse=presence of ≥1 of the following: isolated bone marrow relapse (M3 marrow [representative bone marrow aspirate or biopsy with ≥25% blasts] in the absence of extramedullary involvement) combined bone marrow relapse (M2 [representative bone marrow aspirate or biopsy with ≥5% and <25% blasts] or M3 marrow and ≥1 extramedullary manifestation of acute lymphoblastic leukemia) central nervous system extramedullary relapse testicular extramedullary relapse extramedullary relapse at other sites Months were calculated as days from randomization to event/censor date, divided by 30.5.

Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Related Adverse Events (TRAEs)

Adverse event (AE): any untoward medical occurrence. Serious AE: an AE meeting at least 1 of the following serious criteria: fatal; life-threatening; requires in-patient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; congenital anomaly/birth defect; other medically important serious event. Severity was graded according to the Common Terminology Criteria for AEs (CTCAE) version 4.03: 1=mild, 2=moderate, 3=severe, 4=life-threatening, 5=death. Investigational product (IP) in the HC3 arm refers to dexamethasone, methotrexate, daunorubicin, erwinase, ifosfamide, asparaginase, and vincristine, and in the blinatumomab arm refers to blinatumomab. Treatment-related refers to the assessment of a relationship between IP and the event.

Number of Participants With TEAEs of Interest

TEAEs of interest included capillary leak syndrome (CLS), cytokine release syndrome (CRS), decreased immunoglobulins (DI), elevated liver enzymes (ELE), embolic and thrombotic events (ETE), infections (INF), infusion reactions without considering duration (IRWCD), medication errors (ME), neurologic events (NE), neutropenia and febrile neutropenia (NFN), pancreatitis (PNC), tumor lysis syndrome, leukoencephalopathy, immunogenicity. Severity was graded according to the CTCAE version 4.03: 1=mild, 2=moderate, 3=severe, 4=life-threatening, 5=death.

Number of Participants With Shifts From Baseline Grade 0 or 1 to Worst Postbaseline Grade 3 or 4 Clinical Chemistry and Hematology Values

Severity was graded according to the CTCAE version 4.03: 1=mild, 2=moderate, 3=severe, 4=life-threatening, 5=death. Increases (↑) or decreases (↓) in laboratory value grades (Gr) from baseline (BL) to worst postbaseline (→ PB) grade are presented. NA=not available.

Kaplan-Meier Estimate of 100-Day Mortality After Allogeneic Hematopoietic Stem Cell Transplantation (alloHSCT)

The analysis of 100-day mortality after alloHSCT was assessed for participants who received an alloHSCT while in remission and did not receive any additional anti-leukemic treatment. 100-day mortality after alloHSCT was calculated relative to the date of alloHSCT. The 100-day mortality rate after alloHSCT was defined as the percentage of participants having died up to 100 days after alloHSCT, estimated using the estimated time to death in percent calculated by Kaplan-Meier methods. Participants still alive were censored at the date they were last known to be alive.

Number of Participants With Anti-Blinatumomab Antibodies Postbaseline (Blinatumomab Arm Only)

Participants receiving blinatumomab had blood samples analyzed for binding antibodies. Samples testing positive for binding antibodies were also tested for neutralizing antibodies. Participants who were binding antibody-positive or neutralizing antibody-positive post-baseline with a negative or no result at baseline are presented.

Pharmacokinetics: Concentration at Steady State (Css) (Blinatumomab Arm Only)

Pharmacokinetics: Clearance (CL) (Blinatumomab Arm Only)

Full Information

NCT ID

NCT02393859

First Posted

March 16, 2015

Last Updated

June 24, 2023

Sponsor

Amgen

1. Study Identification

Unique Protocol Identification Number

NCT02393859

Brief Title

Phase 3 Trial of Blinatumomab vs Standard Chemotherapy in Pediatric Subjects With HIgh-Risk (HR) First Relapse B-precursor Acute Lymphoblastic Leukemia (ALL)

Official Title

Phase 3 Trial to Investigate the Efficacy, Safety, and Tolerability of Blinatumomab as Consolidation Therapy Versus Conventional Consolidation Chemotherapy in Pediatric Subjects With HR First Relapse B-precursor ALL

Study Type

Interventional

2. Study Status

Record Verification Date

June 2023

Overall Recruitment Status

Completed

Study Start Date

November 10, 2015 (Actual)

Primary Completion Date

July 17, 2019 (Actual)

Study Completion Date

November 21, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Amgen

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

B-precursor ALL is an aggressive malignant disease. Therapy is usually stratified according to risk characteristics to ensure that appropriate treatment is administered to patients with high-risk of relapse. In general, pediatric treatment regimens are more intense than those employed in adults and include courses of combination chemotherapy. Standard of care chemotherapy is associated with considerable toxicity. There is a lack of novel treatment options for subjects who relapse or are refractory to treatment. Therefore, innovative therapeutic approaches are urgently needed. Blinatumomab is a bispecific single-chain antibody construct designed to link B cells and T cells resulting in T cell activation and a cytotoxic T cell response against CD19 expressing cells. This study will evaluate the event-free survival (EFS) after treatment with blinatumomab when compared to standard of care (SOC) chemotherapy. The effect of blinatumomab on overall survival and reduction of minimal residual disease compared to SOC chemotherapy will also be investigated.

Detailed Description

Patients will be randomized in a 1:1 ratio to receive either one cycle of blinatumomab or one block of standard high-risk consolidation chemotherapy. Blinatumomab is administered as a continuous intravenous infusion (CIVI). One cycle of blinatumomab treatment includes 4 weeks of CIVI of blinatumomab. After completing consolidation therapy, the patients should undergo alloHSCT depending on their bone marrow status. The patients will be followed up until the last subject on study is 36 months following alloHSCT or has died, whichever is first.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Leukemia, Acute Lymphoblastic

Keywords

ALL, High-risk first relapse B-precursor ALL, Precursor Cell Lymphoblastic Leukemia, Neoplasms, Lymphoproliferative Disorders, Immunoproliferative Disorders, Antibodies, Bispecific

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

111 (Actual)

8. Arms, Groups, and Interventions

Arm Title

High Risk Consolidation 3 (HC3) Chemotherapy

Arm Type

Active Comparator

Arm Description

Arm Title

Blinatumomab

Arm Type

Experimental

Arm Description

15 μg/m^2/day as a continuous intravenous infusion (CIVI) for 4 weeks

Intervention Type

Drug

Intervention Name(s)

Blinatumomab

Other Intervention Name(s)

Blincyto, AMG103

Intervention Description

15 μg/m^2/day as a continuous intravenous infusion (CIVI) for 4 weeks

Intervention Type

Drug

Intervention Name(s)

Dexamethasone

Intervention Description

10 mg/m^2/day intravenous (IV) on Days 1-6

Intervention Type

Drug

Intervention Name(s)

Vincrisitne

Intervention Description

1.5 mg/m^2/day IV on Days 1 and 6

Intervention Type

Drug

Intervention Name(s)

Daunorubicin

Intervention Description

30 mg/m^2 IV over 24 hours on Day 5

Intervention Type

Drug

Intervention Name(s)

Methotrexate

Intervention Description

1 g/m^2 IV over 36 hours on Day 1

Intervention Type

Drug

Intervention Name(s)

Ifosfamide

Intervention Description

800 mg/m^2 IV for 1 hour on Days 2-4

Intervention Type

Drug

Intervention Name(s)

PEG-asparaginase

Intervention Description

1000 U/m^2 IV for 2 hours or intramuscularly (IM) on Day 6

Intervention Type

Drug

Intervention Name(s)

Erwinia-asparaginase

Intervention Description

In case of allergic reaction to PEG-asparaginase, participants could change to erwinia-asparaginase, 20,000 units/m2 every 48 hours for a total of 6 doses

Primary Outcome Measure Information:

Title

Kaplan Meier Estimate: Event-Free Survival (EFS; Primary Analysis)

Description

Time Frame

As of the primary analysis data cutoff date (17 July 2019), overall median follow-up time for EFS was 22.4 months.

Title

Kaplan Meier Estimate: EFS (Final Analysis)

Description

Time Frame

At final analysis, overall median follow-up time for EFS was 51.9 months.

Secondary Outcome Measure Information:

Title

Kaplan Meier Estimate: Overall Survival (OS)

Description

Time Frame

At final analysis, overall median follow-up time for OS was 55.2 months.

Title

Percentage of Participants With an MRD Response Within 29 Days of Treatment Initiation

Description

Time Frame

Up to End of Treatment (Cycle 1, Day 29)

Title

Cumulative Incidence of Relapse (CIR)

Description

Time Frame

At final analysis, the overall maximum follow-up time was 82.0 months.

Title

Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Related Adverse Events (TRAEs)

Description

Time Frame

From first dose of IP through the last dose of IP (up to Day 29) plus 30 days.

Title

Number of Participants With TEAEs of Interest

Description

Time Frame

From first dose of IP through the last dose of IP (up to Day 29) plus 30 days.

Title

Number of Participants With Shifts From Baseline Grade 0 or 1 to Worst Postbaseline Grade 3 or 4 Clinical Chemistry and Hematology Values

Description

Time Frame

Up to Day 29 (± 2 days).

Title

Kaplan-Meier Estimate of 100-Day Mortality After Allogeneic Hematopoietic Stem Cell Transplantation (alloHSCT)

Description

Time Frame

From the date of alloHSCT until death/censor date; median follow up time was 1742.0 days for blinatumomab and 1619.0 days for HC3.

Title

Number of Participants With Anti-Blinatumomab Antibodies Postbaseline (Blinatumomab Arm Only)

Description

Time Frame

Day 1 to Day 29.

Title

Pharmacokinetics: Concentration at Steady State (Css) (Blinatumomab Arm Only)

Time Frame

Day 1: at least 10 hours after infusion start and up to 24 hours; Day 15

Title

Pharmacokinetics: Clearance (CL) (Blinatumomab Arm Only)

Time Frame

Day 1: at least 10 hours after infusion start and up to 24 hours; Day 15

10. Eligibility

Sex

All

Minimum Age & Unit of Time

0 Years

Maximum Age & Unit of Time

17 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Subjects with Philadelphia chromosome negative (Ph-) high-risk (HR) first relapse B-precursor acute lymphoblastic leukemia (ALL; as defined by International Berlin-Frankfurt-Muenster study group/International study for treatment of childhood relapsed ALL [I-BFM SG/IntReALL] criteria) Subjects with bone marrow blast percentage < 5% (M1) or bone marrow blast percentage < 25% and ≥5% (M2) marrow at the time of randomization, Age > 28 days and < 18 years at the time of informed consent/assent Subject's legally acceptable representative has provided informed consent when the subject is legally too young to provide informed consent and the subject has provided written assent based on local regulations and/or guidelines prior to any study-specific activities/procedures being initiated Availability of the following material from relapse diagnosis for central analysis of minimal residual disease (MRD) by polymerase chain reaction (PCR): clone-specific primers and reference deoxyribonucleic acid (DNA), as well as primer sequences and analyzed sequences of clonal rearrangements (cases with isolated extramedullary relapse or cases with technical and/or logistic hurdles to obtain and process bone marrow material are exempt from providing this material. In these cases, central MRD analysis only by Flow is permitted). Exclusion Criteria: Clinically relevant central nervous system (CNS) pathology requiring treatment (eg, unstable epilepsy). Evidence of current CNS (CNS 2, CNS 3) involvement by ALL. Subjects with CNS relapse at the time of relapse are eligible if CNS is successfully treated prior to enrollment Peripheral neutrophils < 500/μL prior to start of treatment Peripheral platelets < 50,000/μL prior to start of treatment Currently receiving treatment in another investigational device or drug study or less than 4 weeks since ending treatment on another investigational device or drug study(s), procedures required by IntReALL high-risk (HR) guidelines are allowed Chemotherapy related toxicities that have not resolved to ≤ grade 2 (except for parameters defined in Exclusion Criteria 202, 203, 204, and 217) Symptoms and/or clinical signs and/or radiological and/or sonographic signs that indicate an acute or uncontrolled chronic infection, any other concurrent disease or medical condition that could be exacerbated by the treatment or would seriously complicate compliance with the protocol Abnormal renal or hepatic function prior to start of treatment (day 1) as defined below Abnormal serum creatinine based on age/gender Total bilirubin > 3.0 mg/dL prior to start of treatment (unless related to Gilbert's or Meulengracht disease) Documented infection with human immunodeficiency virus (HIV) Known hypersensitivity to immunoglobulins or any of the products or components to be administered during dosing (excluding asparaginase) Post-menarchal female subject who is pregnant or breastfeeding, or is planning to become pregnant or breastfeed while receiving protocol-specified therapy and for at least 12 months after the last dose of chemotherapy Post-menarchal female subject who is not willing to practice true sexual abstinence or use a highly effective form of contraception while receiving protocol-specified therapy and for at least 12 months after the last dose of chemotherapy Sexually mature male subject who is not willing to practice true sexual abstinence or use a condom with spermicide while receiving protocol-specified therapy and for at least 6 months after last dose of chemotherapy. In countries where spermicide is not available, a condom without spermicide is acceptable Sexually mature male subject who is not willing to abstain from sperm donation while receiving protocol-specified therapy and for at least 6 months after last dose of chemotherapy Subject likely to not be available to complete all protocol-required study visits or procedures, including follow-up visits, and/or to comply with all required study procedures to the best of the subject's and investigator's knowledge History or evidence of any other clinically significant disorder, condition or disease (with the exception of those outlined above) that, in the opinion of the investigator or Amgen physician, if consulted, would pose a risk to subject safety or interfere with the study evaluation, procedures, or completion Placed into an institution due to juridical or regulatory ruling.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Organizational Affiliation

Amgen

Official's Role

Study Director

Facility Information:

Facility Name

Research Site

City

Ciudad Autonoma de Buenos Aires

State/Province

Buenos Aires

ZIP/Postal Code

C1199ABB

Country

Argentina

Facility Name

Research Site

City

Randwick

State/Province

New South Wales

ZIP/Postal Code

2031

Country

Australia

Facility Name

Research Site

City

Westmead

State/Province

New South Wales

ZIP/Postal Code

2145

Country

Australia

Facility Name

Research Site

City

South Brisbane

State/Province

Queensland

ZIP/Postal Code

4101

Country

Australia

Facility Name

Research Site

City

Parkville

State/Province

Victoria

ZIP/Postal Code

3052

Country

Australia

Facility Name

Research Site

City

Graz

ZIP/Postal Code

8036

Country

Austria

Facility Name

Research Site

City

Innsbruck

ZIP/Postal Code

6020

Country

Austria

Facility Name

Research Site

City

Wien

ZIP/Postal Code

1090

Country

Austria

Facility Name

Research Site

City

Brussels

ZIP/Postal Code

1020

Country

Belgium

Facility Name

Research Site

City

Brussels

ZIP/Postal Code

1200

Country

Belgium

Facility Name

Research Site

City

Gent

ZIP/Postal Code

9000

Country

Belgium

Facility Name

Research Site

City

Leuven

ZIP/Postal Code

3000

Country

Belgium

Facility Name

Research Site

City

Liege

ZIP/Postal Code

4000

Country

Belgium

Facility Name

Research Site

City

Curitba

State/Province

Paraná

ZIP/Postal Code

81520-060

Country

Brazil

Facility Name

Research Site

City

Porto Alegre

State/Province

Rio Grande Do Sul

ZIP/Postal Code

90035-903

Country

Brazil

Facility Name

Research Site

City

Sao Paulo

State/Province

São Paulo

ZIP/Postal Code

04039-001

Country

Brazil

Facility Name

Research Site

City

Sao Paulo

State/Province

São Paulo

ZIP/Postal Code

08270-070

Country

Brazil

Facility Name

Research Site

City

Praha 5

ZIP/Postal Code

150 06

Country

Czechia

Facility Name

Research Site

City

Kobenhavn O

ZIP/Postal Code

2100

Country

Denmark

Facility Name

Research Site

City

Bordeaux Cedex

ZIP/Postal Code

33076

Country

France

Facility Name

Research Site

City

Lille

ZIP/Postal Code

59037

Country

France

Facility Name

Research Site

City

Lyon

ZIP/Postal Code

69008

Country

France

Facility Name

Research Site

City

Marseille cedex 5

ZIP/Postal Code

13385

Country

France

Facility Name

Research Site

City

Montpellier cedex 05

ZIP/Postal Code

34295

Country

France

Facility Name

Research Site

City

Nantes cedex 1

ZIP/Postal Code

44093

Country

France

Facility Name

Research Site

City

Paris

ZIP/Postal Code

75012

Country

France

Facility Name

Research Site

City

Paris

ZIP/Postal Code

75019

Country

France

Facility Name

Research Site

City

Strasbourg Cedex

ZIP/Postal Code

67200

Country

France

Facility Name

Research Site

City

Vandoeuvre les Nancy

ZIP/Postal Code

54511

Country

France

Facility Name

Research Site

City

Berlin

ZIP/Postal Code

13353

Country

Germany

Facility Name

Research Site

City

Duesseldorf

ZIP/Postal Code

40225

Country

Germany

Facility Name

Research Site

City

Erlangen

ZIP/Postal Code

91054

Country

Germany

Facility Name

Research Site

City

Essen

ZIP/Postal Code

45122

Country

Germany

Facility Name

Research Site

City

Frankfurt am Main

ZIP/Postal Code

60590

Country

Germany

Facility Name

Research Site

City

Freiburg

ZIP/Postal Code

79106

Country

Germany

Facility Name

Research Site

City

Giessen

ZIP/Postal Code

35392

Country

Germany

Facility Name

Research Site

City

Hamburg

ZIP/Postal Code

20246

Country

Germany

Facility Name

Research Site

City

Hannover

ZIP/Postal Code

30625

Country

Germany

Facility Name

Research Site

City

Jena

ZIP/Postal Code

07740

Country

Germany

Facility Name

Research Site

City

Kiel

ZIP/Postal Code

24105

Country

Germany

Facility Name

Research Site

City

München

ZIP/Postal Code

80337

Country

Germany

Facility Name

Research Site

City

Münster

ZIP/Postal Code

48149

Country

Germany

Facility Name

Research Site

City

Tübingen

ZIP/Postal Code

72076

Country

Germany

Facility Name

Research Site

City

Ulm

ZIP/Postal Code

89075

Country

Germany

Facility Name

Research Site

City

Würzburg

ZIP/Postal Code

97080

Country

Germany

Facility Name

Research Site

City

Goudi

ZIP/Postal Code

11527

Country

Greece

Facility Name

Research Site

City

Haifa

ZIP/Postal Code

3109601

Country

Israel

Facility Name

Research Site

City

Jerusalem

ZIP/Postal Code

9112001

Country

Israel

Facility Name

Research Site

City

Petah Tikva

ZIP/Postal Code

4920235

Country

Israel

Facility Name

Research Site

City

Tel Aviv

ZIP/Postal Code

6423906

Country

Israel

Facility Name

Research Site

City

Tel Hashomer

ZIP/Postal Code

5262000

Country

Israel

Facility Name

Research Site

City

Bologna

ZIP/Postal Code

40138

Country

Italy

Facility Name

Research Site

City

Genova

ZIP/Postal Code

16147

Country

Italy

Facility Name

Research Site

City

Monza (MB)

ZIP/Postal Code

20900

Country

Italy

Facility Name

Research Site

City

Napoli

ZIP/Postal Code

80123

Country

Italy

Facility Name

Research Site

City

Padova

ZIP/Postal Code

35128

Country

Italy

Facility Name

Research Site

City

Pavia

ZIP/Postal Code

27100

Country

Italy

Facility Name

Research Site

City

Roma

ZIP/Postal Code

00161

Country

Italy

Facility Name

Research Site

City

Roma

ZIP/Postal Code

00165

Country

Italy

Facility Name

Research Site

City

Torino

ZIP/Postal Code

10126

Country

Italy

Facility Name

Research Site

City

Mexico

State/Province

Distrito Federal

ZIP/Postal Code

01120

Country

Mexico

Facility Name

Research Site

City

Guadalajara

State/Province

Jalisco

ZIP/Postal Code

44340

Country

Mexico

Facility Name

Research Site

City

Monterrey

State/Province

Nuevo León

ZIP/Postal Code

64460

Country

Mexico

Facility Name

Research Site

City

Rotterdam

ZIP/Postal Code

3015 CN

Country

Netherlands

Facility Name

Research Site

City

Utrecht

ZIP/Postal Code

3584 CS

Country

Netherlands

Facility Name

Research Site

City

Oslo

ZIP/Postal Code

0372

Country

Norway

Facility Name

Research Site

City

Bydgoszcz

ZIP/Postal Code

85-094

Country

Poland

Facility Name

Research Site

City

Krakow

ZIP/Postal Code

30-663

Country

Poland

Facility Name

Research Site

City

Lublin

ZIP/Postal Code

20-093

Country

Poland

Facility Name

Research Site

City

Wroclaw

ZIP/Postal Code

50-556

Country

Poland

Facility Name

Research Site

City

Zabrze

ZIP/Postal Code

41-800

Country

Poland

Facility Name

Research Site

City

Lisboa

ZIP/Postal Code

1099-023

Country

Portugal

Facility Name

Research Site

City

Porto

ZIP/Postal Code

4200-072

Country

Portugal

Facility Name

Research Site

City

Bucharest

ZIP/Postal Code

022328

Country

Romania

Facility Name

Research Site

City

Cluj-Napoca

ZIP/Postal Code

400177

Country

Romania

Facility Name

Research Site

City

Moscow

ZIP/Postal Code

115478

Country

Russian Federation

Facility Name

Research Site

City

Saint Petersburg

ZIP/Postal Code

197022

Country

Russian Federation

Facility Name

Research Site

City

Malaga

State/Province

Andalucía

ZIP/Postal Code

29011

Country

Spain

Facility Name

Research Site

City

Sevilla

State/Province

Andalucía

ZIP/Postal Code

41013

Country

Spain

Facility Name

Research Site

City

Santander

State/Province

Cantabria

ZIP/Postal Code

39008

Country

Spain

Facility Name

Research Site

City

Barcelona

State/Province

Cataluña

ZIP/Postal Code

08035

Country

Spain

Facility Name

Research Site

City

Barcelona

State/Province

Cataluña

ZIP/Postal Code

08041

Country

Spain

Facility Name

Research Site

City

Valencia

State/Province

Comunidad Valenciana

ZIP/Postal Code

46026

Country

Spain

Facility Name

Research Site

City

Santiago de Compostela

State/Province

Galicia

ZIP/Postal Code

15706

Country

Spain

Facility Name

Research Site

City

Boadilla del Monte

State/Province

Madrid

ZIP/Postal Code

28660

Country

Spain

Facility Name

Research Site

City

El Palmar

State/Province

Murcia

ZIP/Postal Code

30120

Country

Spain

Facility Name

Research Site

City

Madrid

ZIP/Postal Code

28009

Country

Spain

Facility Name

Research Site

City

Madrid

ZIP/Postal Code

28046

Country

Spain

Facility Name

Research Site

City

Stockholm

ZIP/Postal Code

171 76

Country

Sweden

Facility Name

Research Site

City

Basel

ZIP/Postal Code

4056

Country

Switzerland

Facility Name

Research Site

City

Zuerich

ZIP/Postal Code

8032

Country

Switzerland

Facility Name

Research Site

City

Adana

ZIP/Postal Code

01130

Country

Turkey

Facility Name

Research Site

City

Antalya

ZIP/Postal Code

07059

Country

Turkey

Facility Name

Research Site

City

Izmir

ZIP/Postal Code

35040

Country

Turkey

Facility Name

Research Site

City

Kayseri

ZIP/Postal Code

38039

Country

Turkey

Facility Name

Research Site

City

Birmingham

ZIP/Postal Code

B4 6NH

Country

United Kingdom

Facility Name

Research Site

City

Bristol

ZIP/Postal Code

BS2 8BJ

Country

United Kingdom

Facility Name

Research Site

City

Glasgow

ZIP/Postal Code

G51 4TF

Country

United Kingdom

Facility Name

Research Site

City

London

ZIP/Postal Code

WC1N 3JH

Country

United Kingdom

Facility Name

Research Site

City

Manchester

ZIP/Postal Code

M13 9WL

Country

United Kingdom

Facility Name

Research Site

City

Newcastle upon Tyne

ZIP/Postal Code

NE1 4LP

Country

United Kingdom

Facility Name

Research Site

City

Sheffield

ZIP/Postal Code

S10 2TH

Country

United Kingdom

Facility Name

Research Site

City

Sutton

ZIP/Postal Code

SM2 5PT

Country

United Kingdom

12. IPD Sharing Statement

Plan to Share IPD

Yes

IPD Sharing Plan Description

De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request

IPD Sharing Time Frame

Data sharing requests relating to this study will be considered beginning 18 months after the study has ended and either 1) the product and indication (or other new use) have been granted marketing authorization in both the US and Europe or 2) clinical development for the product and/or indication discontinues and the data will not be submitted to regulatory authorities. There is no end date for eligibility to submit a data sharing request for this study.

IPD Sharing Access Criteria

Qualified researchers may submit a request containing the research objectives, the Amgen product(s) and Amgen study/studies in scope, endpoints/outcomes of interest, statistical analysis plan, data requirements, publication plan, and qualifications of the researcher(s). In general, Amgen does not grant external requests for individual patient data for the purpose of re-evaluating safety and efficacy issues already addressed in the product labelling. Requests are reviewed by a committee of internal advisors, and if not approved, may be further arbitrated by a Data Sharing Independent Review Panel. Upon approval, information necessary to address the research question will be provided under the terms of a data sharing agreement. This may include anonymized individual patient data and/or available supporting documents, containing fragments of analysis code where provided in analysis specifications. Further details are available at the link below.

IPD Sharing URL

https://www.amgen.com/datasharing

Citations:

PubMed Identifier

35482538

Citation

Locatelli F, Eckert C, Hrusak O, Buldini B, Sartor M, Zugmaier G, Zeng Y, Pilankar D, Morris J, von Stackelberg A. Blinatumomab overcomes poor prognostic impact of measurable residual disease in pediatric high-risk first relapse B-cell precursor acute lymphoblastic leukemia. Pediatr Blood Cancer. 2022 Aug;69(8):e29715. doi: 10.1002/pbc.29715. Epub 2022 Apr 28.

Results Reference

background

Citation

Blinatumomabe em pacientes pediátricos com leucemia linfoblástica aguda B em primeira recidiva de alto risco: um estudo de custo-efetividade. van Beurden-Tan CHY, Ribeiro RA, Seber A, de Martino Lee ML, Marçola M, Schuetz R, Loggetto SR, Maiolino A. Jornal Brasileiro de Economia da Saúde 14(1): 41-50. 10.21115/JBES.v14.n1.p41-50

Results Reference

background

PubMed Identifier

33651091

Citation

Locatelli F, Zugmaier G, Rizzari C, Morris JD, Gruhn B, Klingebiel T, Parasole R, Linderkamp C, Flotho C, Petit A, Micalizzi C, Mergen N, Mohammad A, Kormany WN, Eckert C, Moricke A, Sartor M, Hrusak O, Peters C, Saha V, Vinti L, von Stackelberg A. Effect of Blinatumomab vs Chemotherapy on Event-Free Survival Among Children With High-risk First-Relapse B-Cell Acute Lymphoblastic Leukemia: A Randomized Clinical Trial. JAMA. 2021 Mar 2;325(9):843-854. doi: 10.1001/jama.2021.0987.

Results Reference

background

PubMed Identifier

36482128

Citation

Locatelli F, Zugmaier G, Rizzari C, Morris JD, Gruhn B, Klingebiel T, Parasole R, Linderkamp C, Flotho C, Petit A, Micalizzi C, Zeng Y, Desai R, Kormany WN, Eckert C, Moricke A, Sartor M, Hrusak O, Peters C, Saha V, Vinti L, von Stackelberg A. Improved survival and MRD remission with blinatumomab vs. chemotherapy in children with first high-risk relapse B-ALL. Leukemia. 2023 Jan;37(1):222-225. doi: 10.1038/s41375-022-01770-3. Epub 2022 Dec 8. No abstract available.

Results Reference

background

Links:

URL

http://www.amgentrials.com

Description

AmgenTrials clinical trials website

Learn more about this trial

Phase 3 Trial of Blinatumomab vs Standard Chemotherapy in Pediatric Subjects With HIgh-Risk (HR) First Relapse B-precursor Acute Lymphoblastic Leukemia (ALL)

We'll reach out to this number within 24 hrs

Phase 3 Trial of Blinatumomab vs Standard Chemotherapy in Pediatric Subjects With HIgh-Risk (HR) First Relapse B-precursor Acute Lymphoblastic Leukemia (ALL)

Leukemia, Acute Lymphoblastic

About this trial

Eligibility Criteria

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

1. Study Identification

2. Study Status

3. Sponsor/Collaborators

4. Oversight

5. Study Description

6. Conditions and Keywords

7. Study Design

8. Arms, Groups, and Interventions

10. Eligibility

12. IPD Sharing Statement

Learn more about this trial