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

NCT02412306 | Completed Phase 1 Results DMC

• 1 other identifier: 20130265
• Study Type: interventional
• Target: 66
• Locations: 1 country
• Sites: 16

Brief Summary

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.

Conditions

Relapsed Refractory B Precursor Acute Lymphoblastic Leukemia

Keywords

Amgen

Outcome Measures

Primary Outcomes (3)

• Phase 1b: Number of Participants With Dose-limiting Toxicities

  Dose-limiting toxicities (DLTs) were defined as any Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 grade ≥ 3 adverse event related to blinatumomab, excluding specific CTCAE grade ≥ 3 adverse events considered consistent with the current known safety profile of blinatumomab, CTCAE grade ≥ 3 fever or infection, and laboratory parameters of CTCAE grade ≥ 3 not considered clinically relevant and/or responding to routine medical management.

  Days 1 to 14

• Phase 2: Percentage of Participants With a Best Response of Complete Remission or Complete Remission With Only Partial Hematological Recovery Within 2 Cycles of Treatment

  Hematological assessments were performed from bone marrow biopsy samples. All hematological assessments of bone marrow were reviewed in a central reference laboratory. Hematological remissions were defined by the following criteria: * Complete Remission (CR) is defined as ≤ 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. * Complete Remission With Partial Hematological Recovery (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.

  Within the first 2 cycles of treatment, 12 weeks

• Expansion Cohort: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Related TEAEs

  TEAEs are defined as those that start between the start of the first infusion of blinatumomab and 30 days after the end of the last infusion during the treatment period. The severity of adverse events was assessed by the investigator according to the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 as follows: Grade 1 - Mild AE; Grade 2 - Moderate AE; Grade 3 - Severe AE; Grade 4 - Life-threatening or disabling AE; Grade 5 - Death. The investigator used medical judgment to determine if there was a causal relationship (ie, related, unrelated) between an adverse event and blinatumomab.

  From the start of the first infusion to 30 days after the end of the last infusion; median (min, max) treatment duration was 55.6 (25, 140) and 28.0 (8, 56) days in the adult and pediatric expansion cohorts, respectively.

Secondary Outcomes (21)

• Phase 1b Adults: Percentage of Participants With a Best Response of Complete Remission or Complete Remission With Only Partial Hematological Recovery Within 2 Cycles of Treatment

  Within the first 2 cycles of treatment, 12 weeks

• Phase 1b Pediatric: Percentage of Participants With M1 Remission Within 2 Cycles of Treatment

  The first 2 cycles of treatment, 12 weeks

• Phase 1b and Phase 2: Duration of Response

  Median (minimum [min], maximum [max]) follow-up time was 6.3 (2.4, 13.6) months for Phase 1b and 26.7 (3.0, 28.5) months for Phase 2.

• Phase 1b and Phase 2: Relapse-free Survival

  Median (min, max) follow-up time was 6.3 (2.4, 13.6) months for Phase 1b and 26.7 (3.0, 28.5) months for Phase 2.

• Phase 1b and Phase 2: Overall Survival

  Median (min, max) follow-up time was 6.3 (2.4, 13.6) months for Phase 1b and 26.7 (3.0, 28.5) months for Phase 2.

Study Arms (5)

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

EXPERIMENTAL

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.

Drug: Blinatumomab

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

EXPERIMENTAL

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.

Drug: Blinatumomab

Blinatumomab 9-28 µg/day Phase 2 Adult Population

EXPERIMENTAL

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.

Drug: Blinatumomab

Blinatumomab 9-28 µg/day Adult Expansion Population

EXPERIMENTAL

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.

Drug: Blinatumomab

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

EXPERIMENTAL

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.

Drug: Blinatumomab

Interventions

Blinatumomab DRUG

Continuous intravenous infusion over four weeks per treatment cycle

Also known as: Blincyto®

Blinatumomab 5-15 µg/m^2/day Pediatric Expansion Population; Blinatumomab 5-15 µg/m^2/day Phase 1b Pediatric Population; Blinatumomab 9-28 µg/day Adult Expansion Population; Blinatumomab 9-28 µg/day Phase 1b Adult Population; Blinatumomab 9-28 µg/day Phase 2 Adult Population

Eligibility Criteria

• Age: 0 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Amgen: lead
• Amgen Astellas Biopharma K.K.: collaborator

Study Sites (16)

National Hospital Organization Nagoya Medical Center

Nagoya, Aichi-ken, 460-0001, Japan

Location

Nagoya University Hospital

Nagoya, Aichi-ken, 466-8560, Japan

Location

Kyushu University Hospital

Fukuoka, Fukuoka, 812-8582, Japan

Location

Gunmaken Saiseikai Maebashi Hospital

Maebashi, Gunma, 371-0821, Japan

Location

Sapporo Hokuyu Hospital

Sapporo, Hokkaido, 003-0006, Japan

Location

Kobe University Hospital

Kobe, Hyōgo, 650-0017, Japan

Location

Kanagawa Childrens Medical Center

Yokohama, Kanagawa, 232-8555, Japan

Location

Nagasaki University Hospital

Nagasaki, Nagasaki, 852-8501, Japan

Location

Niigata Cancer Center Hospital

Niigata, Niigata, 951-8566, Japan

Location

Okayama University Hospital

Okayama, Okayama-ken, 700-8558, Japan

Location

Osaka City General Hospital

Osaka, Osaka, 534-0021, Japan

Location

Osaka Metropolitan University Hospital

Osaka, Osaka, 545-8586, Japan

Location

Saitama Childrens Medical Center

Saitama-shi, Saitama, 330-8777, Japan

Location

Jichi Medical University Hospital

Shimotsuke-shi, Tochigi, 329-0498, Japan

Location

National Cancer Center Hospital

Chuo-ku, Tokyo, 104-0045, Japan

Location

National Center for Child Health and Development

Setagaya-ku, Tokyo, 157-8535, Japan

Location

Related Publications (4)

• 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.

  PMID: 32564243 BACKGROUND

• 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.

  PMID: 31971321 BACKGROUND

• 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.

  PMID: 34185953 BACKGROUND

• 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.

  PMID: 35790143 BACKGROUND

Related Links

• AmgenTrials clinical trials website

MeSH Terms

Interventions

blinatumomab

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 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 12, 2015
• First Posted: April 9, 2015
• Study Start: June 4, 2015
• Primary Completion: February 6, 2019
• Study Completion: July 4, 2019
• Last Updated: December 12, 2022
• Results First Posted: January 10, 2020

Record last verified: 2022-12

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

JP (16)