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

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

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.

Study Overview

• Status: Completed
• Conditions: Leukemia, Acute Lymphoblastic
• Intervention / Treatment: Drug: Dexamethasone; Drug: Vincrisitne; Drug: Daunorubicin; Drug: Methotrexate; Drug: Ifosfamide; Drug: PEG-asparaginase; Drug: Erwinia-asparaginase; Drug: Blinatumomab

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.

• Study Type: Interventional
• Enrollment (Actual): 111
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires
    • Ciudad Autonoma de Buenos Aires, Buenos Aires, Argentina, C1199ABB
      • Research Site
• Australia
  • New South Wales
    • Randwick, New South Wales, Australia, 2031
      • Research Site
    • Westmead, New South Wales, Australia, 2145
      • Research Site
  • Queensland
    • South Brisbane, Queensland, Australia, 4101
      • Research Site
  • Victoria
    • Parkville, Victoria, Australia, 3052
      • Research Site
• Austria
  • Graz, Austria, 8036
    • Research Site
  • Innsbruck, Austria, 6020
    • Research Site
  • Wien, Austria, 1090
    • Research Site
• Belgium
  • Brussels, Belgium, 1200
    • Research Site
  • Brussels, Belgium, 1020
    • Research Site
  • Gent, Belgium, 9000
    • Research Site
  • Leuven, Belgium, 3000
    • Research Site
  • Liege, Belgium, 4000
    • Research Site
• Brazil
  • Paraná
    • Curitba, Paraná, Brazil, 81520-060
      • Research Site
  • Rio Grande Do Sul
    • Porto Alegre, Rio Grande Do Sul, Brazil, 90035-903
      • Research Site
  • São Paulo
    • Sao Paulo, São Paulo, Brazil, 08270-070
      • Research Site
    • Sao Paulo, São Paulo, Brazil, 04039-001
      • Research Site
• Czechia
  • Praha 5, Czechia, 150 06
    • Research Site
• Denmark
  • Kobenhavn O, Denmark, 2100
    • Research Site
• France
  • Bordeaux Cedex, France, 33076
    • Research Site
  • Lille, France, 59037
    • Research Site
  • Lyon, France, 69008
    • Research Site
  • Marseille cedex 5, France, 13385
    • Research Site
  • Montpellier cedex 05, France, 34295
    • Research Site
  • Nantes cedex 1, France, 44093
    • Research Site
  • Paris, France, 75012
    • Research Site
  • Paris, France, 75019
    • Research Site
  • Strasbourg Cedex, France, 67200
    • Research Site
  • Vandoeuvre les Nancy, France, 54511
    • Research Site
• Germany
  • Berlin, Germany, 13353
    • Research Site
  • Duesseldorf, Germany, 40225
    • Research Site
  • Erlangen, Germany, 91054
    • Research Site
  • Essen, Germany, 45122
    • Research Site
  • Frankfurt am Main, Germany, 60590
    • Research Site
  • Freiburg, Germany, 79106
    • Research Site
  • Giessen, Germany, 35392
    • Research Site
  • Hamburg, Germany, 20246
    • Research Site
  • Hannover, Germany, 30625
    • Research Site
  • Jena, Germany, 07740
    • Research Site
  • Kiel, Germany, 24105
    • Research Site
  • München, Germany, 80337
    • Research Site
  • Münster, Germany, 48149
    • Research Site
  • Tübingen, Germany, 72076
    • Research Site
  • Ulm, Germany, 89075
    • Research Site
  • Würzburg, Germany, 97080
    • Research Site
• Greece
  • Goudi, Greece, 11527
    • Research Site
• Israel
  • Haifa, Israel, 3109601
    • Research Site
  • Jerusalem, Israel, 9112001
    • Research Site
  • Petah Tikva, Israel, 4920235
    • Research Site
  • Tel Aviv, Israel, 6423906
    • Research Site
  • Tel Hashomer, Israel, 5262000
    • Research Site
• Italy
  • Bologna, Italy, 40138
    • Research Site
  • Genova, Italy, 16147
    • Research Site
  • Monza (MB), Italy, 20900
    • Research Site
  • Napoli, Italy, 80123
    • Research Site
  • Padova, Italy, 35128
    • Research Site
  • Pavia, Italy, 27100
    • Research Site
  • Roma, Italy, 00161
    • Research Site
  • Roma, Italy, 00165
    • Research Site
  • Torino, Italy, 10126
    • Research Site
• Mexico
  • Distrito Federal
    • Mexico, Distrito Federal, Mexico, 01120
      • Research Site
  • Jalisco
    • Guadalajara, Jalisco, Mexico, 44340
      • Research Site
  • Nuevo León
    • Monterrey, Nuevo León, Mexico, 64460
      • Research Site
• Netherlands
  • Rotterdam, Netherlands, 3015 CN
    • Research Site
  • Utrecht, Netherlands, 3584 CS
    • Research Site
• Norway
  • Oslo, Norway, 0372
    • Research Site
• Poland
  • Bydgoszcz, Poland, 85-094
    • Research Site
  • Krakow, Poland, 30-663
    • Research Site
  • Lublin, Poland, 20-093
    • Research Site
  • Wroclaw, Poland, 50-556
    • Research Site
  • Zabrze, Poland, 41-800
    • Research Site
• Portugal
  • Lisboa, Portugal, 1099-023
    • Research Site
  • Porto, Portugal, 4200-072
    • Research Site
• Romania
  • Bucharest, Romania, 022328
    • Research Site
  • Cluj-Napoca, Romania, 400177
    • Research Site
• Russian Federation
  • Moscow, Russian Federation, 115478
    • Research Site
  • Saint Petersburg, Russian Federation, 197022
    • Research Site
• Spain
  • Madrid, Spain, 28046
    • Research Site
  • Madrid, Spain, 28009
    • Research Site
  • Andalucía
    • Malaga, Andalucía, Spain, 29011
      • Research Site
    • Sevilla, Andalucía, Spain, 41013
      • Research Site
  • Cantabria
    • Santander, Cantabria, Spain, 39008
      • Research Site
  • Cataluña
    • Barcelona, Cataluña, Spain, 08035
      • Research Site
    • Barcelona, Cataluña, Spain, 08041
      • Research Site
  • Comunidad Valenciana
    • Valencia, Comunidad Valenciana, Spain, 46026
      • Research Site
  • Galicia
    • Santiago de Compostela, Galicia, Spain, 15706
      • Research Site
  • Madrid
    • Boadilla del Monte, Madrid, Spain, 28660
      • Research Site
  • Murcia
    • El Palmar, Murcia, Spain, 30120
      • Research Site
• Sweden
  • Stockholm, Sweden, 171 76
    • Research Site
• Switzerland
  • Basel, Switzerland, 4056
    • Research Site
  • Zuerich, Switzerland, 8032
    • Research Site
• Turkey
  • Adana, Turkey, 01130
    • Research Site
  • Antalya, Turkey, 07059
    • Research Site
  • Izmir, Turkey, 35040
    • Research Site
  • Kayseri, Turkey, 38039
    • Research Site
• United Kingdom
  • Birmingham, United Kingdom, B4 6NH
    • Research Site
  • Bristol, United Kingdom, BS2 8BJ
    • Research Site
  • Glasgow, United Kingdom, G51 4TF
    • Research Site
  • London, United Kingdom, WC1N 3JH
    • Research Site
  • Manchester, United Kingdom, M13 9WL
    • Research Site
  • Newcastle upon Tyne, United Kingdom, NE1 4LP
    • Research Site
  • Sheffield, United Kingdom, S10 2TH
    • Research Site
  • Sutton, United Kingdom, SM2 5PT
    • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 second to 17 years (Child)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: High Risk Consolidation 3 (HC3) Chemotherapy; 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).	Drug: Dexamethasone; 10 mg/m^2/day intravenous (IV) on Days 1-6; Drug: Vincrisitne; 1.5 mg/m^2/day IV on Days 1 and 6; Drug: Daunorubicin; 30 mg/m^2 IV over 24 hours on Day 5; Drug: Methotrexate; 1 g/m^2 IV over 36 hours on Day 1; Drug: Ifosfamide; 800 mg/m^2 IV for 1 hour on Days 2-4; Drug: PEG-asparaginase; 1000 U/m^2 IV for 2 hours or intramuscularly (IM) on Day 6; Drug: Erwinia-asparaginase; 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
Experimental: Blinatumomab; 15 μg/m^2/day as a continuous intravenous infusion (CIVI) for 4 weeks	Drug: Blinatumomab; 15 μg/m^2/day as a continuous intravenous infusion (CIVI) for 4 weeks; Other Names: Blincyto, AMG103

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	As of the primary analysis data cutoff date (17 July 2019), overall median follow-up time for EFS was 22.4 months.
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.	At final analysis, overall median follow-up time for EFS was 51.9 months.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	At final analysis, overall median follow-up time for OS was 55.2 months.
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.	Up to End of Treatment (Cycle 1, Day 29)
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.	At final analysis, the overall maximum follow-up time was 82.0 months.
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.	From first dose of IP through the last dose of IP (up to Day 29) plus 30 days.
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.	From first dose of IP through the last dose of IP (up to Day 29) plus 30 days.
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.	Up to Day 29 (± 2 days).
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.	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.
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.	Day 1 to Day 29.
Pharmacokinetics: Concentration at Steady State (Css) (Blinatumomab Arm Only)		Day 1: at least 10 hours after infusion start and up to 24 hours; Day 15
Pharmacokinetics: Clearance (CL) (Blinatumomab Arm Only)		Day 1: at least 10 hours after infusion start and up to 24 hours; Day 15

Collaborators and Investigators

• Sponsor: Amgen
• Investigators: Study Director: MD, Amgen

Publications and helpful links

General Publications

• 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.
• 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
• 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.
• 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.
• Caillon M, Brethon B, van Beurden-Tan C, Supiot R, Le Mezo A, Chauny JV, Majer I, Petit A. Cost-Effectiveness of Blinatumomab in Pediatric Patients with High-Risk First-Relapse B-Cell Precursor Acute Lymphoblastic Leukemia in France. Pharmacoecon Open. 2023 Jul;7(4):639-653. doi: 10.1007/s41669-023-00411-4. Epub 2023 Apr 18.

Helpful Links

• AmgenTrials clinical trials website

Study record dates

Study Major Dates

• Study Start (Actual): November 10, 2015
• Primary Completion (Actual): July 17, 2019
• Study Completion (Actual): November 21, 2022

Study Registration Dates

• First Submitted: March 16, 2015
• First Submitted That Met QC Criteria: March 19, 2015
• First Posted (Estimated): March 20, 2015

Study Record Updates

• Last Update Posted (Estimated): February 21, 2024
• Last Update Submitted That Met QC Criteria: February 15, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: Neoplasms; ALL; Lymphoproliferative Disorders; Immunoproliferative Disorders; Antibodies, Bispecific; Precursor Cell Lymphoblastic Leukemia; High-risk first relapse B-precursor ALL
• Additional Relevant MeSH Terms: Pathologic Processes; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Disease Attributes; Leukemia, Lymphoid; Leukemia; Recurrence; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-Inflammatory Agents; Antirheumatic Agents; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Antineoplastic Agents, Alkylating; Alkylating Agents; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Dermatologic Agents; Antibiotics, Antineoplastic; Reproductive Control Agents; Abortifacient Agents, Nonsteroidal; Abortifacient Agents; Folic Acid Antagonists; Dexamethasone; Ifosfamide; Methotrexate; Daunorubicin; Asparaginase; Blinatumomab; Pegaspargase
• Other Study ID Numbers: 20120215; 2014-002476-92 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD 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 Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR