Study of Blinatumomab in Japanese Patients With Relapsed/Refractory B-precursor Acute Lymphoblastic Leukemia

NCT ID: NCT02412306

Last Updated: 2022-12-12

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1/PHASE2

Total Enrollment

66 participants

Study Classification

INTERVENTIONAL

Study Start Date

2015-06-04

Study Completion Date

2019-07-04

Brief Summary

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This is an open-label, combined 2-part multicenter study to evaluate the efficacy, safety, and tolerability of blinatumomab in adult and pediatric Japanese patients with relapsed/refractory B-precursor ALL.

Detailed Description

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The Phase 1b part will investigate the safety, efficacy, pharmacokinetics (PK) and pharmacodynamics (PD) of blinatumomab to determine the maximum tolerated dose (MTD) in both adult and pediatric Japanese patients with relapsed/refractory B-precursor ALL. The Phase 2 part will assess the safety and efficacy of the recommended dose level of blinatumomab identified in the Phase 1b portion of the study in the adult study population.

In June 2017 protocol amendment 4 extended the study to include an expansion cohort of approximately 65 participants to investigate the safety of blinatumomab in participants who did not participate in Phase 1b or Phase 2 of the study. Adult and pediatric patients in the expansion cohort may receive up to 5 cycles of investigational blinatomumab and may receive commercial blinatomumab after a minimum of 2 cycles of the investigational drug.

Conditions

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Relapsed Refractory B Precursor Acute Lymphoblastic Leukemia

Keywords

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Amgen

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Blinatumomab 9-28 µg/day Phase 1b Adult Population

Participants received blinatumomab by continuous intravenous (CIV) infusion over 4 weeks followed by a treatment-free interval of 2 weeks for up to 5 consecutive cycles. The initial dose for adults was 9 µg/day for the first week of cycle 1, escalated to 28 µg/day starting from Week 2 and all cycles thereafter.

Group Type EXPERIMENTAL

Blinatumomab

Intervention Type DRUG

Continuous intravenous infusion over four weeks per treatment cycle

Blinatumomab 5-15 µg/m^2/day Phase 1b Pediatric Population

Participants received blinatumomab by CIV infusion over 4 weeks followed by a treatment-free interval of 2 weeks for up to 5 consecutive cycles. For pediatric participants the initial dose was 5 µg/m²/day for the first week of cycle 1, escalated to 15 µg/m²/day starting from week 2 and all cycles thereafter.

Group Type EXPERIMENTAL

Blinatumomab

Intervention Type DRUG

Continuous intravenous infusion over four weeks per treatment cycle

Blinatumomab 9-28 µg/day Phase 2 Adult Population

Participants received blinatumomab by CIV infusion over 4 weeks followed by a treatment-free interval of 2 weeks for up to 5 consecutive cycles. The initial dose for adults was 9 µg/day for the first week of cycle 1, escalated to 28 µg/day starting from Week 2 and all cycles thereafter.

Group Type EXPERIMENTAL

Blinatumomab

Intervention Type DRUG

Continuous intravenous infusion over four weeks per treatment cycle

Blinatumomab 9-28 µg/day Adult Expansion Population

Participants received blinatumomab by CIV infusion over 4 weeks followed by a treatment-free interval of 2 weeks for up to 5 consecutive cycles. The initial dose for adults was 9 µg/day for the first week of cycle 1, escalated to 28 µg/day starting from Week 2 and all cycles thereafter.

Group Type EXPERIMENTAL

Blinatumomab

Intervention Type DRUG

Continuous intravenous infusion over four weeks per treatment cycle

Blinatumomab 5-15 µg/m^2/day Pediatric Expansion Population

Participants received blinatumomab by CIV infusion over 4 weeks followed by a treatment-free interval of 2 weeks for up to 5 consecutive cycles. For pediatric participants the initial dose was 5 µg/m²/day for the first week of cycle 1, escalated to 15 µg/m²/day starting from week 2 and all cycles thereafter.

Group Type EXPERIMENTAL

Blinatumomab

Intervention Type DRUG

Continuous intravenous infusion over four weeks per treatment cycle

Interventions

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Blinatumomab

Continuous intravenous infusion over four weeks per treatment cycle

Intervention Type DRUG

Other Intervention Names

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Blincyto®

Eligibility Criteria

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Inclusion Criteria

* Age ≥ 18 years old at enrollment
* Subjects with Philadelphia-negative B-precursor ALL, with any of the following:

* Relapsed or refractory after first line therapy with first remission duration ≤ 12 months; or
* Relapsed or refractory after first salvage therapy; or
* Relapsed or refractory within 12 months of allogeneic hematopoietic stem cell transplant (alloHSCT)
* Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1, or 2.
* Greater than 5% blasts in bone marrow


* Age \< 18 years old at enrollment
* Relapsed/refractory disease, defined as one of the following:

* second or later bone marrow relapse;
* any marrow relapse after alloHSCT; or
* Refractory to other treatments:

* For subjects in first relapse: failure to achieve a complete response (CR) following a full standard reinduction chemotherapy regimen
* For subjects who have not achieved a first remission: failure to achieve remission following a full standard induction regimen
* Greater than 5% blasts in bone marrow
* Karnofsky performance status ≥ 50% for subjects ≥ 16 years
* Lansky performance status ≥ 50% for subjects \< 16 years

Exclusion Criteria

* Subjects with Burkitt´s Leukemia according to World Health Organization (WHO) classification
* History or presence of clinically relevant central nervous system (CNS) pathology such as epilepsy, seizure, paresis, aphasia, stroke, severe brain injuries, dementia, Parkinson's disease, cerebellar disease, organic brain syndrome, psychosis; with the exception of well-controlled CNS leukemia
* Active ALL in the CNS or testes
* Current autoimmune disease or history of autoimmune disease with potential CNS involvement
* Autologous HSCT within 6 weeks prior to start of blinatumomab treatment
* AlloHSCT within 12 weeks prior to start of blinatumomab treatment
* Any active acute Graft-versus-Host Disease (GvHD) grade 2-4 according to Glucksberg criteria or active chronic GvHD requiring systemic treatment
Minimum Eligible Age

0 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Amgen Astellas Biopharma K.K.

INDUSTRY

Sponsor Role collaborator

Amgen

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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MD

Role: STUDY_DIRECTOR

Amgen

Locations

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National Hospital Organization Nagoya Medical Center

Nagoya, Aichi-ken, Japan

Site Status

Nagoya University Hospital

Nagoya, Aichi-ken, Japan

Site Status

Kyushu University Hospital

Fukuoka, Fukuoka, Japan

Site Status

Gunmaken Saiseikai Maebashi Hospital

Maebashi, Gunma, Japan

Site Status

Sapporo Hokuyu Hospital

Sapporo, Hokkaido, Japan

Site Status

Kobe University Hospital

Kobe, Hyōgo, Japan

Site Status

Kanagawa Childrens Medical Center

Yokohama, Kanagawa, Japan

Site Status

Nagasaki University Hospital

Nagasaki, Nagasaki, Japan

Site Status

Niigata Cancer Center Hospital

Niigata, Niigata, Japan

Site Status

Okayama University Hospital

Okayama, Okayama-ken, Japan

Site Status

Osaka City General Hospital

Osaka, Osaka, Japan

Site Status

Osaka Metropolitan University Hospital

Osaka, Osaka, Japan

Site Status

Saitama Childrens Medical Center

Saitama-shi, Saitama, Japan

Site Status

Jichi Medical University Hospital

Shimotsuke-shi, Tochigi, Japan

Site Status

National Cancer Center Hospital

Chuo-ku, Tokyo, Japan

Site Status

National Center for Child Health and Development

Setagaya-ku, Tokyo, Japan

Site Status

Countries

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Japan

References

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Horibe K, Morris JD, Tuglus CA, Dos Santos C, Kalabus J, Anderson A, Goto H, Ogawa C. A phase 1b study of blinatumomab in Japanese children with relapsed/refractory B-cell precursor acute lymphoblastic leukemia. Int J Hematol. 2020 Aug;112(2):223-233. doi: 10.1007/s12185-020-02907-9. Epub 2020 Jun 20.

Reference Type BACKGROUND
PMID: 32564243 (View on PubMed)

Kiyoi H, Morris JD, Oh I, Maeda Y, Minami H, Miyamoto T, Sakura T, Iida H, Tuglus CA, Chen Y, Dos Santos C, Kalabus J, Anderson A, Hata T, Nakashima Y, Kobayashi Y. Phase 1b/2 study of blinatumomab in Japanese adults with relapsed/refractory acute lymphoblastic leukemia. Cancer Sci. 2020 Apr;111(4):1314-1323. doi: 10.1111/cas.14322. Epub 2020 Feb 11.

Reference Type BACKGROUND
PMID: 31971321 (View on PubMed)

Kobayashi Y, Oh I, Miyamoto T, Lee WS, Iida H, Minami H, Maeda Y, Jang JH, Yoon SS, Yeh SP, Tran Q, Morris J, Franklin J, Kiyoi H. Efficacy and safety of blinatumomab: Post hoc pooled analysis in Asian adults with relapsed/refractory B-cell precursor acute lymphoblastic leukemia. Asia Pac J Clin Oncol. 2022 Jun;18(3):311-318. doi: 10.1111/ajco.13609. Epub 2021 Jun 29.

Reference Type BACKGROUND
PMID: 34185953 (View on PubMed)

Goto H, Ogawa C, Iida H, Horibe K, Oh I, Takada S, Maeda Y, Minami H, Nakashima Y, Morris JD, Kormany W, Chen Y, Miyamoto T. Safety and Efficacy of Blinatumomab in Japanese Adult and Pediatric Patients with Relapsed/Refractory B-Cell Precursor Acute Lymphoblastic Leukemia: Final Results from an Expansion Cohort. Acta Haematol. 2022;145(6):592-602. doi: 10.1159/000525835. Epub 2022 Jul 5.

Reference Type BACKGROUND
PMID: 35790143 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

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http://www.amgentrials.com

AmgenTrials clinical trials website

Other Identifiers

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20130265

Identifier Type: -

Identifier Source: org_study_id