Efficacy and Safety of the BiTE Antibody Blinatumomab in Chinese Adult Subjects With Relapsed/Refractory B-precursor Acute Lymphoblastic Leukemia (ALL)

NCT03476239 | Completed Phase 3 Results

• 1 other identifier: 20130316
• Study Type: interventional
• Target: 121
• Locations: 1 country
• Sites: 23

Brief Summary

This study is being done to evaluate the rate of hematological response (complete remission/complete remission with partial hematological recovery \[CR/CRh\*\]) induced by blinatumomab in Chinese adults with relapsed/refractory B-precursor acute lymphoblastic leukemia (ALL).

Conditions

Acute Lymphoblastic Leukemia

Keywords

Relapsed; Refractory; B-precursor; Acute Lymphoblastic; Leukemia ALL; Blinatumomab; Chinese Adult Subjects

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants With a Hematological Response of Complete Remission (CR) or Complete Remission With Partial Hematological Recovery (CRh*) During the First 2 Treatment Cycles With Blinatumomab

  A CR is defined as having ≤ 5% blasts in the bone marrow, no evidence of disease, and full recovery of peripheral blood counts (platelets \> 100,000/μL, and absolute neutrophil count \[ANC\] \> 1,000/μL). CRh\* is defined as ≤ 5% blasts in the bone marrow, no evidence of disease and partial recovery of peripheral blood counts: platelets \> 50,000/μl, and ANC \> 500/μl. CR/CRh\* rate is defined as the percentage of participants who achieve CR/CRh\* within 2 cycles of treatment with blinatumomab. Participants without response assessment were accounted for in the denominator when calculating the response rate, ie, these participants were counted as non-responders. The interim analysis was to become the primary analysis by meeting pre-specified efficacy and safety criteria based on an O'Brien-Fleming alpha spending function with the critical boundary 42.2%. Results for both the interim and final analysis are reported.

  Within 2 cycles of treatment (12 weeks)

Secondary Outcomes (15)

• Percentage of Participants With a Hematological Response of Complete Remission (CR) During the First 2 Treatment Cycles With Blinatumomab

  Within 2 cycles of treatment (12 weeks)

• Percentage of Participants With a CR or CRh* or Complete Remission With Incomplete Hematological Recovery Without CRh* (CRi) (CR/CRh*/CRi) During the First 2 Treatment Cycles With Blinatumomab

  Within 2 cycles of treatment (12 weeks)

• Pharmacokinetic (PK) Parameter: Concentration of Blinatumomab at Steady State (Css)

  Cycle 1: Days 2, 15, and 29; Cycle 2: Days 2, 15, and 29 (approximately study days 44, 57, and 71)

• Pharmacokinetic (PK) Parameter: Clearance

  Cycle 1: Days 2, 15 and 29; Cycle 2: Days 2, 15 and 29 (approximately study days 44, 57 and 71)

• Pharmacokinetic (PK) Parameter: Terminal Half-Life

  Cycle 1 Day 29: prior to end of infusion and after the end of infusion at 3 hours and 6 hours

Study Arms (1)

Blinatumomab

EXPERIMENTAL

Treatment consisted of two induction cycles and up to 3 consolidation cycles of treatment for responders. In the first induction cycle, the initial dose of blinatumomab was 9 μg/day for Days 1-7 and then escalated (dose step) to 28 μg/day starting on day 8 (week 2) through day 29 (week 4). This is followed by two weeks without blinatumomab treatment. In subsequent cycles (beginning with the second induction cycle and continuing through consolidation, for applicable participants) 28 μg/day was administered for all 4 weeks of continuous treatment, followed by a treatment-free interval of two weeks.

Drug: Blinatumomab; Drug: Dexamthasone

Interventions

Blinatumomab DRUG

Blinatumomab will be supplied as single-use glass injection vials as a sterile, preservative-free, white to off-white, lyophilized powder for reconstitution and administration by continuous intravenous infusion (CIVI). A single cycle of blinatumomab treatment is 6 weeks in duration, which includes 4 weeks of blinatumomab CIVI followed by a 2 week treatment-free interval. The treatment-free interval may be prolonged by up to 7 days, if deemed necessary by the investigator.

Also known as: BLINCYTO®, AMG 103, MT103

Blinatumomab

Dexamthasone DRUG

Premedication with dexamethasone was intended to prevent cytokine release syndrome (CRS) events associated with blinatumomab treatment. Treatment could start pre-study. Dexamethasone 20 mg IV was administered within 3 hours before start of blinatumomab in each treatment cycle, and within 3 hours before dose step increase.

Blinatumomab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects have provided informed consent/assent prior to initiation of any study-specific activities/procedures or subjects legally acceptable representative has provided informed consent prior to any study-specific activities/procedures being initiated when the subject has any kind of condition that, in the opinion of the investigator, may compromise the ability of the subject to give written informed consent.
• Subjects with Ph-negative B-precursor ALL, with any of the following:
• Primary refractory after induction therapy or who had relapsed within 12 months of first remission or
• Relapsed within 12 months of receiving allogeneic hematopoietic stem cell transplantation (alloHSCT) or
• Relapsed or refractory after first salvage therapy or beyond
• \> 5% blasts in bone marrow (by morphology)
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤ 2
• Age ≥ 18 years at the time of informed consent

You may not qualify if:

• Disease Related
• Subjects with Ph-positive ALL
• Subjects with Burkitt´s Leukemia according to World Health Organization (WHO) classification.
• History or presence of clinically relevant CNS pathology as epilepsy, seizure, paresis, aphasia, stroke, severe brain injuries, dementia, Parkinson's disease, cerebellar disease, organic brain syndrome, and psychosis
• Active ALL in the central nervous system (CNS) (confirmed by cerebrospinal fluid \[CSF\] analysis) or testes
• Isolated extramedullary disease
• Current active autoimmune disease or history of autoimmune disease with potential CNS involvement
• Other Medical Conditions
• History of malignancy other than ALL within 5 years prior to start of protocol-specified therapy with the exception of:
• Malignancy treated with curative intent and with no known active disease present for 5 years before enrollment and felt to be at low risk for recurrence by the treating physician.
• Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease
• Adequately treated cervical carcinoma in situ without evidence of disease.
• Adequately treated breast ductal carcinoma in situ without evidence of disease.
• Prostatic intraepithelial neoplasia without evidence of prostate cancer.
• Known infection with human immunodeficiency virus (HIV) or chronic infection with hepatitis B virus (HBsAg positive) or hepatitis C virus (anti-HCV positive)

Sponsors & Collaborators

• Amgen: lead

Study Sites (23)

Peking University Third Hospital

Beijing, Beijing Municipality, 100191, China

Location

Peking Union Medical College Hospital

Beijing, Beijing Municipality, 100730, China

Location

Chinese People Liberation Army General Hospital

Beijing, Beijing Municipality, 100853, China

Location

Fujian Medical University Union Hospital

Fuzhou, Fujian, 350001, China

Location

Guangdong Provincial Peoples Hospital

Guangzhou, Guangdong, 510080, China

Location

The First Affiliated Hospital of Sun Yat-sen University

Guangzhou, Guangdong, 510080, China

Location

Sun Yat-sen Memorial Hospital, Sun Yat-sen University

Guangzhou, Guangdong, 510120, China

Location

Nanfang Hospital, Southern Medical University

Guangzhou, Guangdong, 510515, China

Location

Henan Cancer Hospital

Zhengzhou, Henan, 450008, China

Location

Tongji Hospital Tongji Medical College Huazhong University of Science and Technology

Wuhan, Hubei, 430030, China

Location

Xiangya Hospital Central South University

Changsha, Hunan, 410008, China

Location

Jiangsu Province Hospital

Nanjing, Jiangsu, 210029, China

Location

The First Affiliated Hospital of Soochow University

Suzhou, Jiangsu, 215006, China

Location

The First Hospital of Jilin University

Changchun, Jilin, 130021, China

Location

The First Hospital of China Medical University

Shenyang, Liaoning, 110001, China

Location

The Second Affiliated Hospital of Xi an Jiaotong University

Xi'an, Shaanxi, 71004, China

Location

West China Hospital, Sichuang University

Chengdu, Sichuan, 610041, China

Location

Institute of Hematology and Blood Diseases Hospital Peking Union Medical College

Tianjin, Tianjin Municipality, 300020, China

Location

The First Affiliated Hospital, College of Medicine, Zhejiang University

Hangzhou, Zhejiang, 310003, China

Location

Second Affiliated Hospital Zhejiang University College of Medicine

Hangzhou, Zhejiang, 310009, China

Location

Peking University International Hosipital

Beijing, 102206, China

Location

Anhui Provincial Hospital

Hefei, 230001, China

Location

Huashan Hospital Affiliated to Fudan University

Shanghai, 200040, China

Location

Related Publications (1)

• Zhou H, Yin Q, Jin J, Liu T, Cai Z, Jiang B, Li D, Sun Z, Li Y, He Y, Ma L, Gao S, Hu J, He A, Du X, Liu D, Zhang X, Ke X, Zhuang J, Han Y, Wang X, Chen Y, Gordon P, Yu D, Zugmaier G, Wang J. Efficacy and safety of blinatumomab in Chinese adults with Ph-negative relapsed/refractory B-cell precursor acute lymphoblastic leukemia: A multicenter open-label single-arm China registrational study. Hematology. 2022 Dec;27(1):917-927. doi: 10.1080/16078454.2022.2111992.

  PMID: 36000952 DERIVED

Related Links

• AmgenTrials clinical trials website

MeSH Terms

Conditions

Precursor Cell Lymphoblastic Leukemia-Lymphoma; Recurrence

Interventions

blinatumomab

Condition Hierarchy (Ancestors)

Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Study Director
• Organization: Amgen Inc.

medinfo@amgen.com

866-572-6436

Study Officials

• MD

  Amgen

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Evaluate the efficacy and safety of blinatumomab in Chinese subjects with relapsed/refractory B-precursor ALL, The study will consist of a screening period, a treatment period, and a follow-up period. Treatment will consist of up to 5 cycles of blinatumomab

Study Record Dates

• First Submitted: March 12, 2018
• First Posted: March 26, 2018
• Study Start: October 18, 2017
• Primary Completion: August 21, 2019
• Study Completion: April 8, 2021
• Last Updated: February 8, 2023
• Results First Posted: September 14, 2020

Record last verified: 2023-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• 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.
• 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 URL below.

Locations

CN (23)