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| Name | Class |
|---|---|
| Amgen Astellas Biopharma K.K. | INDUSTRY |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
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| 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. |
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| 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. |
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| 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. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Blinatumomab | Drug | Continuous intravenous infusion over four weeks per treatment cycle |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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:
| 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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 | 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:
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Adult Subjects Key Inclusion Criteria:
Age ≥ 18 years old at enrollment
Subjects with Philadelphia-negative B-precursor ALL, with any of the following:
Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1, or 2.
Greater than 5% blasts in bone marrow
Pediatric Subjects Key Inclusion Criteria:
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:
Greater than 5% blasts in bone marrow
Karnofsky performance status ≥ 50% for subjects ≥ 16 years
Lansky performance status ≥ 50% for subjects < 16 years
Key Exclusion Criteria
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| Name | Affiliation | Role |
|---|---|---|
| MD | Amgen | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| National Hospital Organization Nagoya Medical Center | Nagoya | Aichi-ken | 460-0001 | Japan | ||
| Nagoya University Hospital |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 32564243 | Background | 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. | |
| 31971321 | Background |
| Label | URL |
|---|---|
| AmgenTrials clinical trials website | View source |
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De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request
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.
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.
After a 2-week screening and pre-phase period, participants were treated in an open-label phase 1b part (adult or pediatric), a phase 2 part (adult), or in an expansion cohort (adult or pediatric).
Study was conducted at 16 centers in Japan. Cohort enrollment periods were: adult phase 1b, from 04 Jun 2015 to 13 Jan 2016; pediatric phase 1b, from 17 Feb 2016 to 20 Jun 2016; adult phase 2, from 11 Apr 2016 to 12 Jun 2017; adult expansion cohort, from 04 Dec 2017 to 13 Nov 2018; pediatric expansion cohort, from 05 Nov 2017 to 05 Sep 2018.
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| ID | Title | Description |
|---|---|---|
| FG000 | Phase 1b: Blinatumomab 9/28 μg/Day (Adults) | 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 was 9 μg/day for the first week of cycle 1, escalated to 28 μg/day starting from week 2 and all cycles thereafter. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Mar 20, 2019 | Dec 20, 2019 |
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| 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. |
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| Within the first 2 cycles of treatment, 12 weeks |
| Phase 1b Pediatric: Percentage of Participants With M1 Remission Within 2 Cycles of Treatment | M1 remission for pediatric participants was defined as ≤ 5% blasts (M1 bone marrow) in the bone marrow and no evidence of disease. | The first 2 cycles of treatment, 12 weeks |
| Phase 1b and Phase 2: Duration of Response | Duration of response was calculated from the date of bone marrow aspiration when response (CR/CRh*) was detected for the first time during the first 2 cycles of treatment until the earlier of the following events:
For a responder who did not report an event and was alive during the study, the end date of duration (censoring) was based on the date of the last available bone marrow aspiration prior to the data cutoff date for the analysis. Participants with response who did not report an event and who died due to reasons other than PD, were censored on the date of death, with death treated as a competing risk. | 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 | Relapse-free survival (RFS) was defined for participants who achieved a response (CR/CRh*) during the first 2 cycles of treatment. RFS was calculated from the date of bone marrow aspiration when response was detected for the first time to the date of bone marrow aspiration at which hematological relapse was first detected or the date of diagnosis on which the hematological or extra medullary relapse was documented or the date of death due to any cause, whichever was earlier. Participants who did not experience hematological relapse and did not die were censored on the date of the last available bone marrow aspiration prior to the data cutoff date for the analysis. | 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 | Overall survival (OS) was calculated from the start date of blinatumomab infusion in the first treatment cycle. All deaths were counted as events on the date of death. Participants still alive were censored on the last documented visit date or the date of the last phone contact when the participant was last known to have been alive. For participants who withdrew their informed consent, only information until the date of withdrawal was used in the analysis. | 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 2: Best Overall Response Within 2 Cycles of Treatment | Best response was defined as one of the following: CR: ≤ 5% blasts in the bone marrow (BM); No evidence of disease; Full recovery of peripheral blood counts: Platelets > 100,000/µl, and absolute neutrophil count (ANC) > 1,000/µl CRh*: ≤ 5% blasts in BM; No evidence of disease; Partial recovery of peripheral blood counts: Platelets > 50,000/µl, and ANC > 500/µl CRi: CR with incomplete count recovery without CRh* Blast free hypoplastic or aplastic BM: ≤ 5 % blasts in BM; No evidence of disease; Insufficient recovery of peripheral blood counts: platelets ≤ 50,000/µl and/or ANC ≤ 500/µl Partial Remission: BM blasts > 5 to < 25% with at least a 50% reduction from baseline Hematological Relapse: > 5% blasts in BM or blasts in peripheral blood after documented CR/CRh* during the study PD: An increase from baseline of ≥ 25% of BM blasts or an absolute increase of ≥ 5,000 cells/µL in the number of circulating leukemia cells. | Within the first 2 cycles of treatment, 12 weeks |
| Phase 2: Percentage of Participants Who Received an Allogeneic Hematopoietic Stem Cell Transplant (HSCT) During Blinatumomab Induced Remission | Participants who were eligible for allogeneic HSCT were those who achieved remission (complete response or complete response with partial recovery of peripheral blood counts) after 2 cycles of blinatumomab treatment, and no further anti-leukemic medication was given before HSCT. | Median (min, max) follow-up time was 26.7 (3.0, 28.5) months. |
| Phase 2: 100-Day Mortality After Allogeneic HSCT | The analysis of 100-day mortality after allogeneic HSCT was assessed for all participants who received an allogeneic HSCT while in any CR following treatment with blinatumomab. 100-day mortality after allogeneic HSCT was calculated relative to the date of allogeneic HSCT. Participants still alive alive were censored on the last documented visit date or the date of the last phone contact when the patient was last known to have been alive. The 100-day mortality rate after allogeneic HSCT was defined as the percentage of participants having died up to 100 days after allogeneic HSCT estimated using the estimated time to death in percent calculated by Kaplan-Meier methods. | 100 days, from the date of allogeneic HSCT; median (min, max) follow-up time was 26.7 (3.0, 28.5) |
| Phase 1b and Phase 2: Number of Participants With 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 108 (56, 140), 56.0 (5, 84), and 56.0 (11, 115) days in adult phase 1b, adult phase 2 and pediatric phase 1b cohort respectively. |
| Phase 1b and Phase 2: Serum Blinatumomab Concentration at Steady State | The steady-state concentration (Css) of serum blinatumomab was summarized as the average of the observed concentrations collected after 5 half-lives or after 24 hours from the start of continuous IV infusion. Cycle 1, day 2 values represent steady-state concentration after CIV with the initial dose of blinatumomab (9 µg/day for adults and 5 µg/m²/day for pediatric patients). All other time points were measured after the dose step to 28 µg/day (adults) / 15 µg/m²/day (pediatric participants). | After 24 hours from the start of infusion: Cycle 1 (before dose step) day 2; Cycle 1 (after dose step) days 15 and 29; Cycle 2 onwards day 8 (pediatric and adult), days 15 and 29 (adult). |
| Phase 1b and Phase 2: Systemic Clearance of Blinatumomab | Systemic clearance (CL) was calculated as CL = R0/Css, where R0 is the infusion rate (µg/hour or µg/m²/hour). | After 24 hours from the start of infusion: Cycle 1 (before dose step) day 2; Cycle 1 (after dose step) days 15 and 29; Cycle 2 onwards day 8 (pediatric and adult), days 15 and 29 (adult). |
| Phase 1b and Phase 2: Terminal Half-life of Blinatumomab | Cycle 1 day 1 predose, 2, 6 (adults), 10, 24 hours; day 8 (prior to dose step) 0 hour (adults); day 15 any time during infusion; day 29 prior to end of infusion, 1 (adults), 2, 4 (adults), 6 hours after end of infusion |
| Phase 1b and Phase 2: Volume of Distribution of Blinatumomab | Cycle 1 day 1 predose, 2, 6 (adults), 10, 24 hours; day 8 (prior to dose step) 0 hour (adults); day 15 any time during infusion; day 29 prior to end of infusion, 1 (adults), 2, 4 (adults), 6 hours after end of infusion |
| Phase 1b and Phase 2: Number of Participants Who Developed Anti-Blinatumomab Antibodies | Antibodies to blinatumomab were detected using an electrochemiluminescence (ECL)-based assay. | Day 1 before first dose; cycles 1 and 2 day 29, 6 hours after end of infusion; 30 days after last dose. |
| Phase 1b and Phase 2: Interleukin-2 Concentration | The activation of immune effector cells was monitored by the measurement of peripheral blood cytokine levels including interleukin (IL)-2, IL-6, IL-10, tumor necrosis factor (TNF)-α and interferon gamma (IFN-γ) using multiplex cytometric bead assays. The lower limit of quantification (LLOQ) was 125 pg/mL and the limit of detection (LOD) was 20 pg/mL. For calculations of mean cytokine concentrations at every time point across all participants, samples with concentrations below LLOQ were included in the calculation as ½ LLOQ (= 62.5 pg/mL); samples with values below LOD were included as ½ LOD (= 10 pg/mL). | Adults: cycle 1, day 1: 2, 6, 10, 24 hrs after infusion start; day 8: 2, 6, 10 hrs after dose step. Cycles 2-5, day 1: 6 hrs after infusion start. Pediatric: cycle 1, day 1: 6, 10, 24 hrs after infusion start; Cycles 2-5, day 1: 6 hrs after infusion start |
| Phase 1b and Phase 2: Interleukin-6 Concentration | The activation of immune effector cells was monitored by the measurement of peripheral blood cytokine levels including interleukin (IL)-2, IL-6, IL-10, tumor necrosis factor (TNF)-α and interferon gamma (IFN-γ) using multiplex cytometric bead assays. The lower limit of quantification (LLOQ) was 125 pg/mL and the limit of detection (LOD) was 20 pg/mL. For calculations of mean cytokine concentrations at every time point across all participants, samples with concentrations below LLOQ were included in the calculation as ½ LLOQ (= 62.5 pg/mL); samples with values below LOD were included as ½ LOD (= 10 pg/mL). | Adults: cycle 1, day 1: 2, 6, 10, 24 hrs after infusion start; day 8: 2, 6, 10 hrs after dose step. Cycles 2-5, day 1: 6 hrs after infusion start. Pediatric: cycle 1, day 1: 6, 10, 24 hrs after infusion start; Cycles 2-5, day 1: 6 hrs after infusion start |
| Phase 1b and Phase 2: Interleukin-10 Concentration | The activation of immune effector cells was monitored by the measurement of peripheral blood cytokine levels including interleukin (IL)-2, IL-6, IL-10, tumor necrosis factor (TNF)-α and interferon gamma (IFN-γ) using multiplex cytometric bead assays. The lower limit of quantification (LLOQ) was 125 pg/mL and the limit of detection (LOD) was 20 pg/mL. For calculations of mean cytokine concentrations at every time point across all participants, samples with concentrations below LLOQ were included in the calculation as ½ LLOQ (= 62.5 pg/mL); samples with values below LOD were included as ½ LOD (= 10 pg/mL). | Adults: cycle 1, day 1: 2, 6, 10, 24 hrs after infusion start; day 8: 2, 6, 10 hrs after dose step. Cycles 2-5, day 1: 6 hrs after infusion start. Pediatric: cycle 1, day 1: 6, 10, 24 hrs after infusion start; Cycles 2-5, day 1: 6 hrs after infusion start |
| Phase 1b and Phase 2: Tumor Necrosis Factor-Alpha (TNFα) Concentration | The activation of immune effector cells was monitored by the measurement of peripheral blood cytokine levels including interleukin (IL)-2, IL-6, IL-10, tumor necrosis factor (TNF)-α and interferon gamma (IFN-γ) using multiplex cytometric bead assays. The lower limit of quantification (LLOQ) was 125 pg/mL and the limit of detection (LOD) was 20 pg/mL. For calculations of mean cytokine concentrations at every time point across all participants, samples with concentrations below LLOQ were included in the calculation as ½ LLOQ (= 62.5 pg/mL); samples with values below LOD were included as ½ LOD (= 10 pg/mL). | Adults: cycle 1, day 1: 2, 6, 10, 24 hrs after infusion start; day 8: 2, 6, 10 hrs after dose step. Cycles 2-5, day 1: 6 hrs after infusion start. Pediatric: cycle 1, day 1: 6, 10, 24 hrs after infusion start; Cycles 2-5, day 1: 6 hrs after infusion start |
| Phase 1b and Phase 2: Interferon Gamma (IFN-γ) Concentration | The activation of immune effector cells was monitored by the measurement of peripheral blood cytokine levels including interleukin (IL)-2, IL-6, IL-10, tumor necrosis factor (TNF)-α and interferon gamma (IFN-γ) using multiplex cytometric bead assays. The lower limit of quantification (LLOQ) was 125 pg/mL and the limit of detection (LOD) was 20 pg/mL. For calculations of mean cytokine concentrations at every time point across all participants, samples with concentrations below LLOQ were included in the calculation as ½ LLOQ (= 62.5 pg/mL); samples with values below LOD were included as ½ LOD (= 10 pg/mL). | Adults: cycle 1, day 1: 2, 6, 10, 24 hrs after infusion start; day 8: 2, 6, 10 hrs after dose step. Cycles 2-5, day 1: 6 hrs after infusion start. Pediatric: cycle 1, day 1: 6, 10, 24 hrs after infusion start; Cycles 2-5, day 1: 6 hrs after infusion start |
| Expansion Cohort Adult: 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:
| Within the first 2 cycles of treatment, 12 weeks |
| Expansion Cohort Pediatric: Percentage of Participants With M1 Remission Within 2 Cycles of Treatment | M1 remission for pediatric participants was defined as ≤ 5% blasts (M1 bone marrow) in the bone marrow and no evidence of disease. | Within the first 2 cycles of treatment, 12 weeks |
| Nagoya |
| Aichi-ken |
| 466-8560 |
| Japan |
| Kyushu University Hospital | Fukuoka | Fukuoka | 812-8582 | Japan |
| Gunmaken Saiseikai Maebashi Hospital | Maebashi | Gunma | 371-0821 | Japan |
| Sapporo Hokuyu Hospital | Sapporo | Hokkaido | 003-0006 | Japan |
| Kobe University Hospital | Kobe | Hyōgo | 650-0017 | Japan |
| Kanagawa Childrens Medical Center | Yokohama | Kanagawa | 232-8555 | Japan |
| Nagasaki University Hospital | Nagasaki | Nagasaki | 852-8501 | Japan |
| Niigata Cancer Center Hospital | Niigata | Niigata | 951-8566 | Japan |
| Okayama University Hospital | Okayama | Okayama-ken | 700-8558 | Japan |
| Osaka City General Hospital | Osaka | Osaka | 534-0021 | Japan |
| Osaka Metropolitan University Hospital | Osaka | Osaka | 545-8586 | Japan |
| Saitama Childrens Medical Center | Saitama-shi | Saitama | 330-8777 | Japan |
| Jichi Medical University Hospital | Shimotsuke-shi | Tochigi | 329-0498 | Japan |
| National Cancer Center Hospital | Chuo-ku | Tokyo | 104-0045 | Japan |
| National Center for Child Health and Development | Setagaya-ku | Tokyo | 157-8535 | Japan |
| 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. |
| 34185953 | 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. |
| 35790143 | 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. |
| FG001 |
| Phase 1b: Blinatumomab 5/15 µg/m²/Day (Pediatric) |
Participants received blinatumomab by CIV over 4 weeks followed by a treatment-free interval of 2 weeks for up to 5 consecutive cycles. 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. |
| FG002 | Phase 2: Blinatumomab 9/28 μg/Day (Adults) | Participants received blinatumomab by continuous intravenous infusion over 4 weeks followed by a treatment-free interval of 2 weeks for up to 5 consecutive cycles. The initial dose was 9 μg/day for the first week of cycle 1, escalated to 28 μg/day starting from Week 2 and all cycles thereafter. |
| FG003 | Expansion Cohort: Blinatumomab 9/28 μg/Day (Adults) | Participants received blinatumomab by continuous intravenous infusion over 4 weeks followed by a treatment-free interval of 2 weeks for up to 5 consecutive cycles. The initial dose was 9 μg/day for the first week of cycle 1, escalated to 28 μg/day starting from Week 2 and all cycles thereafter. |
| FG004 | Expansion Cohort: Blinatumomab 5/15 µg/m²/Day (Pediatric) | Participants received blinatumomab by continuous intravenous infusion over 4 weeks followed by a treatment-free interval of 2 weeks for up to 5 consecutive cycles. 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. |
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| NOT COMPLETED |
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| ID | Title | Description |
|---|---|---|
| BG000 | Phase 1b: Blinatumomab 9/28 μg/Day (Adults) | 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 was 9 μg/day for the first week of cycle 1, escalated to 28 μg/day starting from week 2 and all cycles thereafter. |
| BG001 | Phase 1b: Blinatumomab 5/15 µg/m²/Day (Pediatric) | Participants received blinatumomab by CIV over 4 weeks followed by a treatment-free interval of 2 weeks for up to 5 consecutive cycles. 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. |
| BG002 | Phase 2: Blinatumomab 9/28 μg/Day (Adults) | Participants received blinatumomab by continuous intravenous infusion over 4 weeks followed by a treatment-free interval of 2 weeks for up to 5 consecutive cycles. The initial dose was 9 μg/day for the first week of cycle 1, escalated to 28 μg/day starting from Week 2 and all cycles thereafter. |
| BG003 | Expansion Cohort: Blinatumomab 9/28 μg/Day (Adults) | Participants received blinatumomab by continuous intravenous infusion over 4 weeks followed by a treatment-free interval of 2 weeks for up to 5 consecutive cycles. The initial dose was 9 μg/day for the first week of cycle 1, escalated to 28 μg/day starting from Week 2 and all cycles thereafter. |
| BG004 | Expansion Cohort: Blinatumomab 5/15 µg/m²/Day (Pediatric) | Participants received blinatumomab by continuous intravenous infusion over 4 weeks followed by a treatment-free interval of 2 weeks for up to 5 consecutive cycles. 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. |
| BG005 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Customized | Count of Participants | Participants |
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| Sex: Female, Male | Count of Participants | Participants |
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| Race/Ethnicity, Customized | Count of Participants | Participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||
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| Primary | 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. | Phase 1b participants in who received any infusion of blinatumomab. | Posted | Count of Participants | Participants | Days 1 to 14 |
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| Primary | 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:
| Phase 2 participants who received any infusion of blinatumomab. | Posted | Number | 95% Confidence Interval | percentage of participants | Within the first 2 cycles of treatment, 12 weeks |
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| Secondary | 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 | 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:
| Phase 1b adult participants who received any infusion of blinatumomab. | Posted | Number | 95% Confidence Interval | percentage of participants | Within the first 2 cycles of treatment, 12 weeks |
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| Secondary | Phase 1b Pediatric: Percentage of Participants With M1 Remission Within 2 Cycles of Treatment | M1 remission for pediatric participants was defined as ≤ 5% blasts (M1 bone marrow) in the bone marrow and no evidence of disease. | Phase 1b pediatric participants who received any infusion of blinatumomab. | Posted | Number | 95% Confidence Interval | percentage of participants | The first 2 cycles of treatment, 12 weeks |
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| Secondary | Phase 1b and Phase 2: Duration of Response | Duration of response was calculated from the date of bone marrow aspiration when response (CR/CRh*) was detected for the first time during the first 2 cycles of treatment until the earlier of the following events:
For a responder who did not report an event and was alive during the study, the end date of duration (censoring) was based on the date of the last available bone marrow aspiration prior to the data cutoff date for the analysis. Participants with response who did not report an event and who died due to reasons other than PD, were censored on the date of death, with death treated as a competing risk. | Phase 1b and Phase 2 participants who received any infusion of blinatumomab and achieved CR/CRh* during the first 2 cycles of treatment. | Posted | Median | 95% Confidence Interval | months | 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. |
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| Secondary | Phase 1b and Phase 2: Relapse-free Survival | Relapse-free survival (RFS) was defined for participants who achieved a response (CR/CRh*) during the first 2 cycles of treatment. RFS was calculated from the date of bone marrow aspiration when response was detected for the first time to the date of bone marrow aspiration at which hematological relapse was first detected or the date of diagnosis on which the hematological or extra medullary relapse was documented or the date of death due to any cause, whichever was earlier. Participants who did not experience hematological relapse and did not die were censored on the date of the last available bone marrow aspiration prior to the data cutoff date for the analysis. | Phase 1b and Phase 2 participants who received any infusion of blinatumomab and achieved CR/CRh* during the first 2 cycles of treatment. | Posted | Median | 95% Confidence Interval | months | 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. |
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| Secondary | Phase 1b and Phase 2: Overall Survival | Overall survival (OS) was calculated from the start date of blinatumomab infusion in the first treatment cycle. All deaths were counted as events on the date of death. Participants still alive were censored on the last documented visit date or the date of the last phone contact when the participant was last known to have been alive. For participants who withdrew their informed consent, only information until the date of withdrawal was used in the analysis. | Phase 1b and Phase 2 participants who received any infusion of blinatumomab. | Posted | Median | 95% Confidence Interval | months | 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. |
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| Secondary | Phase 2: Best Overall Response Within 2 Cycles of Treatment | Best response was defined as one of the following: CR: ≤ 5% blasts in the bone marrow (BM); No evidence of disease; Full recovery of peripheral blood counts: Platelets > 100,000/µl, and absolute neutrophil count (ANC) > 1,000/µl CRh*: ≤ 5% blasts in BM; No evidence of disease; Partial recovery of peripheral blood counts: Platelets > 50,000/µl, and ANC > 500/µl CRi: CR with incomplete count recovery without CRh* Blast free hypoplastic or aplastic BM: ≤ 5 % blasts in BM; No evidence of disease; Insufficient recovery of peripheral blood counts: platelets ≤ 50,000/µl and/or ANC ≤ 500/µl Partial Remission: BM blasts > 5 to < 25% with at least a 50% reduction from baseline Hematological Relapse: > 5% blasts in BM or blasts in peripheral blood after documented CR/CRh* during the study PD: An increase from baseline of ≥ 25% of BM blasts or an absolute increase of ≥ 5,000 cells/µL in the number of circulating leukemia cells. | Phase 2 participants who received any infusion of blinatumomab. | Posted | Count of Participants | Participants | Within the first 2 cycles of treatment, 12 weeks |
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| Secondary | Phase 2: Percentage of Participants Who Received an Allogeneic Hematopoietic Stem Cell Transplant (HSCT) During Blinatumomab Induced Remission | Participants who were eligible for allogeneic HSCT were those who achieved remission (complete response or complete response with partial recovery of peripheral blood counts) after 2 cycles of blinatumomab treatment, and no further anti-leukemic medication was given before HSCT. | Phase 2 participants who received any infusion of blinatumomab. | Posted | Number | percentage of participants | Median (min, max) follow-up time was 26.7 (3.0, 28.5) months. |
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| Secondary | Phase 2: 100-Day Mortality After Allogeneic HSCT | The analysis of 100-day mortality after allogeneic HSCT was assessed for all participants who received an allogeneic HSCT while in any CR following treatment with blinatumomab. 100-day mortality after allogeneic HSCT was calculated relative to the date of allogeneic HSCT. Participants still alive alive were censored on the last documented visit date or the date of the last phone contact when the patient was last known to have been alive. The 100-day mortality rate after allogeneic HSCT was defined as the percentage of participants having died up to 100 days after allogeneic HSCT estimated using the estimated time to death in percent calculated by Kaplan-Meier methods. | Phase 2 participants who received an allogeneic HSCT. | Posted | Number | percentage of participants | 100 days, from the date of allogeneic HSCT; median (min, max) follow-up time was 26.7 (3.0, 28.5) |
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| Secondary | Phase 1b and Phase 2: Number of Participants With 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. | Phase 1b and Phase 2 participants who received any infusion of blinatumomab. | Posted | Count of Participants | Participants | From the start of the first infusion to 30 days after the end of the last infusion; median (min, max) treatment duration was 108 (56, 140), 56.0 (5, 84), and 56.0 (11, 115) days in adult phase 1b, adult phase 2 and pediatric phase 1b cohort respectively. |
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| Secondary | Phase 1b and Phase 2: Serum Blinatumomab Concentration at Steady State | The steady-state concentration (Css) of serum blinatumomab was summarized as the average of the observed concentrations collected after 5 half-lives or after 24 hours from the start of continuous IV infusion. Cycle 1, day 2 values represent steady-state concentration after CIV with the initial dose of blinatumomab (9 µg/day for adults and 5 µg/m²/day for pediatric patients). All other time points were measured after the dose step to 28 µg/day (adults) / 15 µg/m²/day (pediatric participants). | Phase 1b and phase 2 participants who received any infusion of blinatumomab and had at least one pharmacokinetic sample collected, with available data at each time point. | Posted | Mean | Standard Deviation | pg/mL | After 24 hours from the start of infusion: Cycle 1 (before dose step) day 2; Cycle 1 (after dose step) days 15 and 29; Cycle 2 onwards day 8 (pediatric and adult), days 15 and 29 (adult). |
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| Secondary | Phase 1b and Phase 2: Systemic Clearance of Blinatumomab | Systemic clearance (CL) was calculated as CL = R0/Css, where R0 is the infusion rate (µg/hour or µg/m²/hour). | Phase 1b and phase 2 participants who received any infusion of blinatumomab and had at least one pharmacokinetic sample collected. | Posted | Mean | Standard Deviation | liters/hour | After 24 hours from the start of infusion: Cycle 1 (before dose step) day 2; Cycle 1 (after dose step) days 15 and 29; Cycle 2 onwards day 8 (pediatric and adult), days 15 and 29 (adult). |
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| Secondary | Phase 1b and Phase 2: Terminal Half-life of Blinatumomab | Phase 1b and phase 2 participants who received any infusion of blinatumomab and had at least one pharmacokinetic sample collected with available data. | Posted | Mean | Standard Deviation | hours | Cycle 1 day 1 predose, 2, 6 (adults), 10, 24 hours; day 8 (prior to dose step) 0 hour (adults); day 15 any time during infusion; day 29 prior to end of infusion, 1 (adults), 2, 4 (adults), 6 hours after end of infusion |
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| Secondary | Phase 1b and Phase 2: Volume of Distribution of Blinatumomab | Phase 1b and phase 2 participants who received any infusion of blinatumomab and had at least one pharmacokinetic sample collected with available data. | Posted | Mean | Standard Deviation | liters | Cycle 1 day 1 predose, 2, 6 (adults), 10, 24 hours; day 8 (prior to dose step) 0 hour (adults); day 15 any time during infusion; day 29 prior to end of infusion, 1 (adults), 2, 4 (adults), 6 hours after end of infusion |
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| Secondary | Phase 1b and Phase 2: Number of Participants Who Developed Anti-Blinatumomab Antibodies | Antibodies to blinatumomab were detected using an electrochemiluminescence (ECL)-based assay. | Phase 1b and Phase 2 participants who received any infusion of blinatumomab. | Posted | Count of Participants | Participants | Day 1 before first dose; cycles 1 and 2 day 29, 6 hours after end of infusion; 30 days after last dose. |
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| Secondary | Phase 1b and Phase 2: Interleukin-2 Concentration | The activation of immune effector cells was monitored by the measurement of peripheral blood cytokine levels including interleukin (IL)-2, IL-6, IL-10, tumor necrosis factor (TNF)-α and interferon gamma (IFN-γ) using multiplex cytometric bead assays. The lower limit of quantification (LLOQ) was 125 pg/mL and the limit of detection (LOD) was 20 pg/mL. For calculations of mean cytokine concentrations at every time point across all participants, samples with concentrations below LLOQ were included in the calculation as ½ LLOQ (= 62.5 pg/mL); samples with values below LOD were included as ½ LOD (= 10 pg/mL). | Phase 1b and phase 2 participants who received any infusion of blinatumomab and had at least one pharmacodynamic sample collected, with available data at each time point. | Posted | Mean | Standard Deviation | pg/mL | Adults: cycle 1, day 1: 2, 6, 10, 24 hrs after infusion start; day 8: 2, 6, 10 hrs after dose step. Cycles 2-5, day 1: 6 hrs after infusion start. Pediatric: cycle 1, day 1: 6, 10, 24 hrs after infusion start; Cycles 2-5, day 1: 6 hrs after infusion start |
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| Secondary | Phase 1b and Phase 2: Interleukin-6 Concentration | The activation of immune effector cells was monitored by the measurement of peripheral blood cytokine levels including interleukin (IL)-2, IL-6, IL-10, tumor necrosis factor (TNF)-α and interferon gamma (IFN-γ) using multiplex cytometric bead assays. The lower limit of quantification (LLOQ) was 125 pg/mL and the limit of detection (LOD) was 20 pg/mL. For calculations of mean cytokine concentrations at every time point across all participants, samples with concentrations below LLOQ were included in the calculation as ½ LLOQ (= 62.5 pg/mL); samples with values below LOD were included as ½ LOD (= 10 pg/mL). | Phase 1b and phase 2 participants who received any infusion of blinatumomab and had at least one pharmacodynamic sample collected, with available data at each time point. | Posted | Mean | Standard Deviation | pg/mL | Adults: cycle 1, day 1: 2, 6, 10, 24 hrs after infusion start; day 8: 2, 6, 10 hrs after dose step. Cycles 2-5, day 1: 6 hrs after infusion start. Pediatric: cycle 1, day 1: 6, 10, 24 hrs after infusion start; Cycles 2-5, day 1: 6 hrs after infusion start |
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| Secondary | Phase 1b and Phase 2: Interleukin-10 Concentration | The activation of immune effector cells was monitored by the measurement of peripheral blood cytokine levels including interleukin (IL)-2, IL-6, IL-10, tumor necrosis factor (TNF)-α and interferon gamma (IFN-γ) using multiplex cytometric bead assays. The lower limit of quantification (LLOQ) was 125 pg/mL and the limit of detection (LOD) was 20 pg/mL. For calculations of mean cytokine concentrations at every time point across all participants, samples with concentrations below LLOQ were included in the calculation as ½ LLOQ (= 62.5 pg/mL); samples with values below LOD were included as ½ LOD (= 10 pg/mL). | Phase 1b and phase 2 participants who received any infusion of blinatumomab and had at least one pharmacodynamic sample collected, with available data at each time point. | Posted | Mean | Standard Deviation | pg/mL | Adults: cycle 1, day 1: 2, 6, 10, 24 hrs after infusion start; day 8: 2, 6, 10 hrs after dose step. Cycles 2-5, day 1: 6 hrs after infusion start. Pediatric: cycle 1, day 1: 6, 10, 24 hrs after infusion start; Cycles 2-5, day 1: 6 hrs after infusion start |
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| Secondary | Phase 1b and Phase 2: Tumor Necrosis Factor-Alpha (TNFα) Concentration | The activation of immune effector cells was monitored by the measurement of peripheral blood cytokine levels including interleukin (IL)-2, IL-6, IL-10, tumor necrosis factor (TNF)-α and interferon gamma (IFN-γ) using multiplex cytometric bead assays. The lower limit of quantification (LLOQ) was 125 pg/mL and the limit of detection (LOD) was 20 pg/mL. For calculations of mean cytokine concentrations at every time point across all participants, samples with concentrations below LLOQ were included in the calculation as ½ LLOQ (= 62.5 pg/mL); samples with values below LOD were included as ½ LOD (= 10 pg/mL). | Phase 1b and phase 2 participants who received any infusion of blinatumomab and had at least one pharmacodynamic sample collected, with available data at each time point. | Posted | Mean | Standard Deviation | pg/mL | Adults: cycle 1, day 1: 2, 6, 10, 24 hrs after infusion start; day 8: 2, 6, 10 hrs after dose step. Cycles 2-5, day 1: 6 hrs after infusion start. Pediatric: cycle 1, day 1: 6, 10, 24 hrs after infusion start; Cycles 2-5, day 1: 6 hrs after infusion start |
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| Secondary | Phase 1b and Phase 2: Interferon Gamma (IFN-γ) Concentration | The activation of immune effector cells was monitored by the measurement of peripheral blood cytokine levels including interleukin (IL)-2, IL-6, IL-10, tumor necrosis factor (TNF)-α and interferon gamma (IFN-γ) using multiplex cytometric bead assays. The lower limit of quantification (LLOQ) was 125 pg/mL and the limit of detection (LOD) was 20 pg/mL. For calculations of mean cytokine concentrations at every time point across all participants, samples with concentrations below LLOQ were included in the calculation as ½ LLOQ (= 62.5 pg/mL); samples with values below LOD were included as ½ LOD (= 10 pg/mL). | Phase 1b participants who received any infusion of blinatumomab and had at least one pharmacodynamic sample collected, with available data at each time point. | Posted | Mean | Standard Deviation | pg/mL | Adults: cycle 1, day 1: 2, 6, 10, 24 hrs after infusion start; day 8: 2, 6, 10 hrs after dose step. Cycles 2-5, day 1: 6 hrs after infusion start. Pediatric: cycle 1, day 1: 6, 10, 24 hrs after infusion start; Cycles 2-5, day 1: 6 hrs after infusion start |
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| Primary | 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. | Expansion Cohort participants in the who received any infusion of blinatumomab. | Posted | Number | participants | 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. |
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| Secondary | Expansion Cohort Adult: 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:
| Expansion Cohort adult participants who received any infusion of blinatumomab. | Posted | Number | 95% Confidence Interval | percentage of participants | Within the first 2 cycles of treatment, 12 weeks |
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| Secondary | Expansion Cohort Pediatric: Percentage of Participants With M1 Remission Within 2 Cycles of Treatment | M1 remission for pediatric participants was defined as ≤ 5% blasts (M1 bone marrow) in the bone marrow and no evidence of disease. | Expansion Cohort pediatric participants who received any infusion of blinatumomab. | Posted | Number | 95% Confidence Interval | percentage of participants | Within the first 2 cycles of treatment, 12 weeks |
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The median treatment duration for blinatumomab was 108 days for Adult Phase 1b Cohort, 56 days for Pediatric Phase 1b Cohort, 56 days for Adult Phase 2 Cohort, 55.6 days for Adult Expansion Cohort and 28 days for Pediatric Expansion Cohort
All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
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| EG000 | Phase 1b: Blinatumomab 9/28 μg/Day (Adults) | 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 was 9 μg/day for the first week of cycle 1, escalated to 28 μg/day starting from week 2 and all cycles thereafter. | 5 | 5 | 0 | 5 | 5 | 5 |
| EG001 | Phase 1b: Blinatumomab 5/15 µg/m²/Day (Pediatric) | Participants received blinatumomab by CIV over 4 weeks followed by a treatment-free interval of 2 weeks for up to 5 consecutive cycles. 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. | 7 | 9 | 1 | 9 | 9 | 9 |
| EG002 | Phase 2: Blinatumomab 9/28 μg/Day (Adults) | Participants received blinatumomab by continuous intravenous infusion over 4 weeks followed by a treatment-free interval of 2 weeks for up to 5 consecutive cycles. The initial dose was 9 μg/day for the first week of cycle 1, escalated to 28 μg/day starting from Week 2 and all cycles thereafter. | 15 | 21 | 7 | 21 | 21 | 21 |
| EG003 | Expansion Cohort: Blinatumomab 9/28 μg/Day (Adults) | Participants received blinatumomab by continuous intravenous infusion over 4 weeks followed by a treatment-free interval of 2 weeks for up to 5 consecutive cycles. The initial dose was 9 μg/day for the first week of cycle 1, escalated to 28 μg/day starting from Week 2 and all cycles thereafter. | 0 | 14 | 2 | 14 | 14 | 14 |
| EG004 | Expansion Cohort: Blinatumomab 5/15 µg/m²/Day (Pediatric) | Participants received blinatumomab by continuous intravenous infusion over 4 weeks followed by a treatment-free interval of 2 weeks for up to 5 consecutive cycles. 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. | 2 | 17 | 3 | 17 | 16 | 17 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Colitis | Gastrointestinal disorders | MedDRA 22.0 | Systematic Assessment |
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| Cytokine release syndrome | Immune system disorders | MedDRA 22.0 | Systematic Assessment |
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| Bacteraemia | Infections and infestations | MedDRA 22.0 | Systematic Assessment |
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| Neutrophil count decreased | Investigations | MedDRA 22.0 | Systematic Assessment |
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| Decreased appetite | Metabolism and nutrition disorders | MedDRA 22.0 | Systematic Assessment |
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| Tumour lysis syndrome | Metabolism and nutrition disorders | MedDRA 22.0 | Systematic Assessment |
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| Shock haemorrhagic | Vascular disorders | MedDRA 22.0 | Systematic Assessment |
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| Stomatitis | Gastrointestinal disorders | MedDRA 22.0 | Systematic Assessment |
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| Disease progression | General disorders | MedDRA 22.0 | Systematic Assessment |
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| Multiple organ dysfunction syndrome | General disorders | MedDRA 22.0 | Systematic Assessment |
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| Device related sepsis | Infections and infestations | MedDRA 22.0 | Systematic Assessment |
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| Sepsis | Infections and infestations | MedDRA 22.0 | Systematic Assessment |
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| Overdose | Injury, poisoning and procedural complications | MedDRA 22.0 | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA 22.0 | Systematic Assessment |
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| Bone marrow failure | Blood and lymphatic system disorders | MedDRA 22.0 | Systematic Assessment |
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| Disseminated intravascular coagulation | Blood and lymphatic system disorders | MedDRA 22.0 | Systematic Assessment |
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| Febrile neutropenia | Blood and lymphatic system disorders | MedDRA 22.0 | Systematic Assessment |
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| Leukopenia | Blood and lymphatic system disorders | MedDRA 22.0 | Systematic Assessment |
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| Lymphopenia | Blood and lymphatic system disorders | MedDRA 22.0 | Systematic Assessment |
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| Neutropenia | Blood and lymphatic system disorders | MedDRA 22.0 | Systematic Assessment |
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| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA 22.0 | Systematic Assessment |
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| Cardiac failure | Cardiac disorders | MedDRA 22.0 | Systematic Assessment |
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| Sinus bradycardia | Cardiac disorders | MedDRA 22.0 | Systematic Assessment |
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| Steroid withdrawal syndrome | Endocrine disorders | MedDRA 22.0 | Systematic Assessment |
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| Conjunctival haemorrhage | Eye disorders | MedDRA 22.0 | Systematic Assessment |
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| Dry eye | Eye disorders | MedDRA 22.0 | Systematic Assessment |
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| Photophobia | Eye disorders | MedDRA 22.0 | Systematic Assessment |
| |
| Vitreous floaters | Eye disorders | MedDRA 22.0 | Systematic Assessment |
| |
| Abdominal distension | Gastrointestinal disorders | MedDRA 22.0 | Systematic Assessment |
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| Abdominal pain | Gastrointestinal disorders | MedDRA 22.0 | Systematic Assessment |
| |
| Abdominal pain upper | Gastrointestinal disorders | MedDRA 22.0 | Systematic Assessment |
| |
| Aphthous ulcer | Gastrointestinal disorders | MedDRA 22.0 | Systematic Assessment |
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| Constipation | Gastrointestinal disorders | MedDRA 22.0 | Systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA 22.0 | Systematic Assessment |
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| Dyspepsia | Gastrointestinal disorders | MedDRA 22.0 | Systematic Assessment |
| |
| Gastritis | Gastrointestinal disorders | MedDRA 22.0 | Systematic Assessment |
| |
| Gingival swelling | Gastrointestinal disorders | MedDRA 22.0 | Systematic Assessment |
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| Nausea | Gastrointestinal disorders | MedDRA 22.0 | Systematic Assessment |
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| Oral pain | Gastrointestinal disorders | MedDRA 22.0 | Systematic Assessment |
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| Pancreatitis | Gastrointestinal disorders | MedDRA 22.0 | Systematic Assessment |
| |
| Proctitis | Gastrointestinal disorders | MedDRA 22.0 | Systematic Assessment |
| |
| Stomatitis | Gastrointestinal disorders | MedDRA 22.0 | Systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA 22.0 | Systematic Assessment |
| |
| Chest pain | General disorders | MedDRA 22.0 | Systematic Assessment |
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| Fatigue | General disorders | MedDRA 22.0 | Systematic Assessment |
| |
| Localised oedema | General disorders | MedDRA 22.0 | Systematic Assessment |
| |
| Malaise | General disorders | MedDRA 22.0 | Systematic Assessment |
| |
| Oedema | General disorders | MedDRA 22.0 | Systematic Assessment |
| |
| Pain | General disorders | MedDRA 22.0 | Systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA 22.0 | Systematic Assessment |
| |
| Hyperbilirubinaemia | Hepatobiliary disorders | MedDRA 22.0 | Systematic Assessment |
| |
| Liver disorder | Hepatobiliary disorders | MedDRA 22.0 | Systematic Assessment |
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| Liver injury | Hepatobiliary disorders | MedDRA 22.0 | Systematic Assessment |
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| Acute graft versus host disease | Immune system disorders | MedDRA 22.0 | Systematic Assessment |
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| Cytokine release syndrome | Immune system disorders | MedDRA 22.0 | Systematic Assessment |
| |
| Hypogammaglobulinaemia | Immune system disorders | MedDRA 22.0 | Systematic Assessment |
| |
| Bronchopulmonary aspergillosis | Infections and infestations | MedDRA 22.0 | Systematic Assessment |
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| Conjunctivitis | Infections and infestations | MedDRA 22.0 | Systematic Assessment |
| |
| Cystitis | Infections and infestations | MedDRA 22.0 | Systematic Assessment |
| |
| Cytomegalovirus infection | Infections and infestations | MedDRA 22.0 | Systematic Assessment |
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| Device related infection | Infections and infestations | MedDRA 22.0 | Systematic Assessment |
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| Gingivitis | Infections and infestations | MedDRA 22.0 | Systematic Assessment |
| |
| Hepatitis B | Infections and infestations | MedDRA 22.0 | Systematic Assessment |
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| Herpes zoster | Infections and infestations | MedDRA 22.0 | Systematic Assessment |
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| Infection | Infections and infestations | MedDRA 22.0 | Systematic Assessment |
| |
| Nasopharyngitis | Infections and infestations | MedDRA 22.0 | Systematic Assessment |
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| Otitis media | Infections and infestations | MedDRA 22.0 | Systematic Assessment |
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| Pneumonia | Infections and infestations | MedDRA 22.0 | Systematic Assessment |
| |
| Sepsis | Infections and infestations | MedDRA 22.0 | Systematic Assessment |
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| Staphylococcal sepsis | Infections and infestations | MedDRA 22.0 | Systematic Assessment |
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| Upper respiratory tract infection | Infections and infestations | MedDRA 22.0 | Systematic Assessment |
| |
| Contusion | Injury, poisoning and procedural complications | MedDRA 22.0 | Systematic Assessment |
| |
| Infusion related reaction | Injury, poisoning and procedural complications | MedDRA 22.0 | Systematic Assessment |
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| Wrist fracture | Injury, poisoning and procedural complications | MedDRA 22.0 | Systematic Assessment |
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| Activated partial thromboplastin time prolonged | Investigations | MedDRA 22.0 | Systematic Assessment |
| |
| Alanine aminotransferase increased | Investigations | MedDRA 22.0 | Systematic Assessment |
| |
| Amylase increased | Investigations | MedDRA 22.0 | Systematic Assessment |
| |
| Aspartate aminotransferase increased | Investigations | MedDRA 22.0 | Systematic Assessment |
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| Blood alkaline phosphatase increased | Investigations | MedDRA 22.0 | Systematic Assessment |
| |
| Blood bilirubin increased | Investigations | MedDRA 22.0 | Systematic Assessment |
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| Blood glucose decreased | Investigations | MedDRA 22.0 | Systematic Assessment |
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| Blood uric acid increased | Investigations | MedDRA 22.0 | Systematic Assessment |
| |
| Gamma-glutamyltransferase increased | Investigations | MedDRA 22.0 | Systematic Assessment |
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| Glucose urine present | Investigations | MedDRA 22.0 | Systematic Assessment |
| |
| Hepatic enzyme increased | Investigations | MedDRA 22.0 | Systematic Assessment |
| |
| Immunoglobulins decreased | Investigations | MedDRA 22.0 | Systematic Assessment |
| |
| International normalised ratio increased | Investigations | MedDRA 22.0 | Systematic Assessment |
| |
| Lipase increased | Investigations | MedDRA 22.0 | Systematic Assessment |
| |
| Lymphocyte count decreased | Investigations | MedDRA 22.0 | Systematic Assessment |
| |
| Neutrophil count decreased | Investigations | MedDRA 22.0 | Systematic Assessment |
| |
| Oxygen saturation decreased | Investigations | MedDRA 22.0 | Systematic Assessment |
| |
| Platelet count decreased | Investigations | MedDRA 22.0 | Systematic Assessment |
| |
| Prothrombin time prolonged | Investigations | MedDRA 22.0 | Systematic Assessment |
| |
| Serum ferritin increased | Investigations | MedDRA 22.0 | Systematic Assessment |
| |
| Weight decreased | Investigations | MedDRA 22.0 | Systematic Assessment |
| |
| Weight increased | Investigations | MedDRA 22.0 | Systematic Assessment |
| |
| White blood cell count decreased | Investigations | MedDRA 22.0 | Systematic Assessment |
| |
| Decreased appetite | Metabolism and nutrition disorders | MedDRA 22.0 | Systematic Assessment |
| |
| Fluid retention | Metabolism and nutrition disorders | MedDRA 22.0 | Systematic Assessment |
| |
| Hypercalcaemia | Metabolism and nutrition disorders | MedDRA 22.0 | Systematic Assessment |
| |
| Hyperglycaemia | Metabolism and nutrition disorders | MedDRA 22.0 | Systematic Assessment |
| |
| Hyperkalaemia | Metabolism and nutrition disorders | MedDRA 22.0 | Systematic Assessment |
| |
| Hyperlipidaemia | Metabolism and nutrition disorders | MedDRA 22.0 | Systematic Assessment |
| |
| Hyperuricaemia | Metabolism and nutrition disorders | MedDRA 22.0 | Systematic Assessment |
| |
| Hypoalbuminaemia | Metabolism and nutrition disorders | MedDRA 22.0 | Systematic Assessment |
| |
| Hypocalcaemia | Metabolism and nutrition disorders | MedDRA 22.0 | Systematic Assessment |
| |
| Hypokalaemia | Metabolism and nutrition disorders | MedDRA 22.0 | Systematic Assessment |
| |
| Hypomagnesaemia | Metabolism and nutrition disorders | MedDRA 22.0 | Systematic Assessment |
| |
| Hyponatraemia | Metabolism and nutrition disorders | MedDRA 22.0 | Systematic Assessment |
| |
| Hypophosphataemia | Metabolism and nutrition disorders | MedDRA 22.0 | Systematic Assessment |
| |
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA 22.0 | Systematic Assessment |
| |
| Arthritis | Musculoskeletal and connective tissue disorders | MedDRA 22.0 | Systematic Assessment |
| |
| Musculoskeletal pain | Musculoskeletal and connective tissue disorders | MedDRA 22.0 | Systematic Assessment |
| |
| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA 22.0 | Systematic Assessment |
| |
| Myopathy | Musculoskeletal and connective tissue disorders | MedDRA 22.0 | Systematic Assessment |
| |
| Neck pain | Musculoskeletal and connective tissue disorders | MedDRA 22.0 | Systematic Assessment |
| |
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA 22.0 | Systematic Assessment |
| |
| Pain in jaw | Musculoskeletal and connective tissue disorders | MedDRA 22.0 | Systematic Assessment |
| |
| Spinal osteoarthritis | Musculoskeletal and connective tissue disorders | MedDRA 22.0 | Systematic Assessment |
| |
| Spinal pain | Musculoskeletal and connective tissue disorders | MedDRA 22.0 | Systematic Assessment |
| |
| Acute lymphocytic leukaemia | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 22.0 | Systematic Assessment |
| |
| Central nervous system leukaemia | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 22.0 | Systematic Assessment |
| |
| Leukaemic infiltration extramedullary | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 22.0 | Systematic Assessment |
| |
| Altered state of consciousness | Nervous system disorders | MedDRA 22.0 | Systematic Assessment |
| |
| Aphasia | Nervous system disorders | MedDRA 22.0 | Systematic Assessment |
| |
| Facial paralysis | Nervous system disorders | MedDRA 22.0 | Systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA 22.0 | Systematic Assessment |
| |
| Hypoaesthesia | Nervous system disorders | MedDRA 22.0 | Systematic Assessment |
| |
| Intention tremor | Nervous system disorders | MedDRA 22.0 | Systematic Assessment |
| |
| Lethargy | Nervous system disorders | MedDRA 22.0 | Systematic Assessment |
| |
| Peripheral sensory neuropathy | Nervous system disorders | MedDRA 22.0 | Systematic Assessment |
| |
| Seizure | Nervous system disorders | MedDRA 22.0 | Systematic Assessment |
| |
| Somnolence | Nervous system disorders | MedDRA 22.0 | Systematic Assessment |
| |
| Tremor | Nervous system disorders | MedDRA 22.0 | Systematic Assessment |
| |
| Agitation | Psychiatric disorders | MedDRA 22.0 | Systematic Assessment |
| |
| Delirium | Psychiatric disorders | MedDRA 22.0 | Systematic Assessment |
| |
| Insomnia | Psychiatric disorders | MedDRA 22.0 | Systematic Assessment |
| |
| Sleep disorder | Psychiatric disorders | MedDRA 22.0 | Systematic Assessment |
| |
| Cystitis haemorrhagic | Renal and urinary disorders | MedDRA 22.0 | Systematic Assessment |
| |
| Renal disorder | Renal and urinary disorders | MedDRA 22.0 | Systematic Assessment |
| |
| Balanoposthitis | Reproductive system and breast disorders | MedDRA 22.0 | Systematic Assessment |
| |
| Metrorrhagia | Reproductive system and breast disorders | MedDRA 22.0 | Systematic Assessment |
| |
| Pelvic pain | Reproductive system and breast disorders | MedDRA 22.0 | Systematic Assessment |
| |
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA 22.0 | Systematic Assessment |
| |
| Epistaxis | Respiratory, thoracic and mediastinal disorders | MedDRA 22.0 | Systematic Assessment |
| |
| Hiccups | Respiratory, thoracic and mediastinal disorders | MedDRA 22.0 | Systematic Assessment |
| |
| Rhinorrhoea | Respiratory, thoracic and mediastinal disorders | MedDRA 22.0 | Systematic Assessment |
| |
| Acne | Skin and subcutaneous tissue disorders | MedDRA 22.0 | Systematic Assessment |
| |
| Alopecia | Skin and subcutaneous tissue disorders | MedDRA 22.0 | Systematic Assessment |
| |
| Asteatosis | Skin and subcutaneous tissue disorders | MedDRA 22.0 | Systematic Assessment |
| |
| Dermatitis contact | Skin and subcutaneous tissue disorders | MedDRA 22.0 | Systematic Assessment |
| |
| Dry skin | Skin and subcutaneous tissue disorders | MedDRA 22.0 | Systematic Assessment |
| |
| Erythema | Skin and subcutaneous tissue disorders | MedDRA 22.0 | Systematic Assessment |
| |
| Ingrowing nail | Skin and subcutaneous tissue disorders | MedDRA 22.0 | Systematic Assessment |
| |
| Palmar-plantar erythrodysaesthesia syndrome | Skin and subcutaneous tissue disorders | MedDRA 22.0 | Systematic Assessment |
| |
| Rash | Skin and subcutaneous tissue disorders | MedDRA 22.0 | Systematic Assessment |
| |
| Rash maculo-papular | Skin and subcutaneous tissue disorders | MedDRA 22.0 | Systematic Assessment |
| |
| Urticaria | Skin and subcutaneous tissue disorders | MedDRA 22.0 | Systematic Assessment |
| |
| Hypertension | Vascular disorders | MedDRA 22.0 | Systematic Assessment |
| |
| Hypotension | Vascular disorders | MedDRA 22.0 | Systematic Assessment |
| |
| Hypoglobulinaemia | Blood and lymphatic system disorders | MedDRA 22.0 | Systematic Assessment |
| |
| Pancytopenia | Blood and lymphatic system disorders | MedDRA 22.0 | Systematic Assessment |
| |
| Thrombotic microangiopathy | Blood and lymphatic system disorders | MedDRA 22.0 | Systematic Assessment |
| |
| Arrhythmia | Cardiac disorders | MedDRA 22.0 | Systematic Assessment |
| |
| Ventricular tachycardia | Cardiac disorders | MedDRA 22.0 | Systematic Assessment |
| |
| Glaucoma | Eye disorders | MedDRA 22.0 | Systematic Assessment |
| |
| Dental caries | Gastrointestinal disorders | MedDRA 22.0 | Systematic Assessment |
| |
| Gastrointestinal disorder | Gastrointestinal disorders | MedDRA 22.0 | Systematic Assessment |
| |
| Haemorrhoids | Gastrointestinal disorders | MedDRA 22.0 | Systematic Assessment |
| |
| Lip pain | Gastrointestinal disorders | MedDRA 22.0 | Systematic Assessment |
| |
| Oral disorder | Gastrointestinal disorders | MedDRA 22.0 | Systematic Assessment |
| |
| Proctalgia | Gastrointestinal disorders | MedDRA 22.0 | Systematic Assessment |
| |
| Salivary gland pain | Gastrointestinal disorders | MedDRA 22.0 | Systematic Assessment |
| |
| Catheter site pain | General disorders | MedDRA 22.0 | Systematic Assessment |
| |
| Chills | General disorders | MedDRA 22.0 | Systematic Assessment |
| |
| Disease progression | General disorders | MedDRA 22.0 | Systematic Assessment |
| |
| Face oedema | General disorders | MedDRA 22.0 | Systematic Assessment |
| |
| Infusion site extravasation | General disorders | MedDRA 22.0 | Systematic Assessment |
| |
| Non-cardiac chest pain | General disorders | MedDRA 22.0 | Systematic Assessment |
| |
| Oedema peripheral | General disorders | MedDRA 22.0 | Systematic Assessment |
| |
| Cholecystitis | Hepatobiliary disorders | MedDRA 22.0 | Systematic Assessment |
| |
| Drug-induced liver injury | Hepatobiliary disorders | MedDRA 22.0 | Systematic Assessment |
| |
| Hepatic function abnormal | Hepatobiliary disorders | MedDRA 22.0 | Systematic Assessment |
| |
| Hepatic pain | Hepatobiliary disorders | MedDRA 22.0 | Systematic Assessment |
| |
| Engraftment syndrome | Immune system disorders | MedDRA 22.0 | Systematic Assessment |
| |
| Graft versus host disease | Immune system disorders | MedDRA 22.0 | Systematic Assessment |
| |
| Hypersensitivity | Immune system disorders | MedDRA 22.0 | Systematic Assessment |
| |
| Bacteraemia | Infections and infestations | MedDRA 22.0 | Systematic Assessment |
| |
| Folliculitis | Infections and infestations | MedDRA 22.0 | Systematic Assessment |
| |
| Fungal infection | Infections and infestations | MedDRA 22.0 | Systematic Assessment |
| |
| Gastroenteritis norovirus | Infections and infestations | MedDRA 22.0 | Systematic Assessment |
| |
| Paronychia | Infections and infestations | MedDRA 22.0 | Systematic Assessment |
| |
| Pharyngitis | Infections and infestations | MedDRA 22.0 | Systematic Assessment |
| |
| Sialoadenitis | Infections and infestations | MedDRA 22.0 | Systematic Assessment |
| |
| Skin candida | Infections and infestations | MedDRA 22.0 | Systematic Assessment |
| |
| Arthropod bite | Injury, poisoning and procedural complications | MedDRA 22.0 | Systematic Assessment |
| |
| Antithrombin III decreased | Investigations | MedDRA 22.0 | Systematic Assessment |
| |
| Bilirubin conjugated increased | Investigations | MedDRA 22.0 | Systematic Assessment |
| |
| Blast cell count increased | Investigations | MedDRA 22.0 | Systematic Assessment |
| |
| Blood cholesterol increased | Investigations | MedDRA 22.0 | Systematic Assessment |
| |
| Blood creatinine increased | Investigations | MedDRA 22.0 | Systematic Assessment |
| |
| Blood fibrinogen decreased | Investigations | MedDRA 22.0 | Systematic Assessment |
| |
| Hypernatraemia | Metabolism and nutrition disorders | MedDRA 22.0 | Systematic Assessment |
| |
| Hypertriglyceridaemia | Metabolism and nutrition disorders | MedDRA 22.0 | Systematic Assessment |
| |
| Hypoglycaemia | Metabolism and nutrition disorders | MedDRA 22.0 | Systematic Assessment |
| |
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 22.0 | Systematic Assessment |
| |
| Haemorrhage intracranial | Nervous system disorders | MedDRA 22.0 | Systematic Assessment |
| |
| Movement disorder | Nervous system disorders | MedDRA 22.0 | Systematic Assessment |
| |
| Posterior reversible encephalopathy syndrome | Nervous system disorders | MedDRA 22.0 | Systematic Assessment |
| |
| Wernicke's encephalopathy | Nervous system disorders | MedDRA 22.0 | Systematic Assessment |
| |
| Disorientation | Psychiatric disorders | MedDRA 22.0 | Systematic Assessment |
| |
| Hallucination | Psychiatric disorders | MedDRA 22.0 | Systematic Assessment |
| |
| Cystitis noninfective | Renal and urinary disorders | MedDRA 22.0 | Systematic Assessment |
| |
| Pollakiuria | Renal and urinary disorders | MedDRA 22.0 | Systematic Assessment |
| |
| Urinary retention | Renal and urinary disorders | MedDRA 22.0 | Systematic Assessment |
| |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA 22.0 | Systematic Assessment |
| |
| Hypoxia | Respiratory, thoracic and mediastinal disorders | MedDRA 22.0 | Systematic Assessment |
| |
| Laryngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA 22.0 | Systematic Assessment |
| |
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA 22.0 | Systematic Assessment |
| |
| Dermatitis acneiform | Skin and subcutaneous tissue disorders | MedDRA 22.0 | Systematic Assessment |
| |
| Dermatitis diaper | Skin and subcutaneous tissue disorders | MedDRA 22.0 | Systematic Assessment |
| |
| Dermatitis exfoliative generalised | Skin and subcutaneous tissue disorders | MedDRA 22.0 | Systematic Assessment |
| |
| Eczema | Skin and subcutaneous tissue disorders | MedDRA 22.0 | Systematic Assessment |
| |
| Pruritus | Skin and subcutaneous tissue disorders | MedDRA 22.0 | Systematic Assessment |
| |
| Hot flush | Vascular disorders | MedDRA 22.0 | Systematic Assessment |
|
The Clinical Trial Agreement generally does not restrict an investigator's discussion of trial results after completion. The Agreement permits Amgen a limited period of time to review material discussing trial results (typically up to 45 days and possible extension). Amgen may remove confidential information, but authors have final control and approval of publication content. For multicenter studies, the investigator agrees not to publish any results before the first multi-center publication.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Study Director | Amgen Inc. | 866-572-6436 | medinfo@amgen.com |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Apr 12, 2019 | Dec 20, 2019 | SAP_001.pdf |
| ID | Term |
|---|---|
| C510808 | blinatumomab |
Not provided
Not provided
Not provided
| 2 to 6 years |
|
| 7 to 17 years |
|
| 18 to 34 years |
|
| 35 to 54 years |
|
| 55 to 64 years |
|
| ≥ 65 years |
|
| Male |
|
| Participants |
|
|
| Participants |
|
|
|
| OG001 | Phase 1b: Blinatumomab 5/15 µg/m²/Day (Pediatric) | Participants received blinatumomab by CIV over 4 weeks followed by a treatment-free interval of 2 weeks for up to 5 consecutive cycles. 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. |
| OG002 | Phase 2: Blinatumomab 9/28 μg/Day (Adults) | Participants received blinatumomab by continuous intravenous infusion over 4 weeks followed by a treatment-free interval of 2 weeks for up to 5 consecutive cycles. The initial dose was 9 μg/day for the first week of cycle 1, escalated to 28 μg/day starting from Week 2 and all cycles thereafter. |
|
|
| OG002 | Phase 2: Blinatumomab 9/28 μg/Day (Adults) | Participants received blinatumomab by continuous intravenous infusion over 4 weeks followed by a treatment-free interval of 2 weeks for up to 5 consecutive cycles. The initial dose was 9 μg/day for the first week of cycle 1, escalated to 28 μg/day starting from Week 2 and all cycles thereafter. |
|
|
| OG002 | Phase 2: Blinatumomab 9/28 μg/Day (Adults) | Participants received blinatumomab by continuous intravenous infusion over 4 weeks followed by a treatment-free interval of 2 weeks for up to 5 consecutive cycles. The initial dose was 9 μg/day for the first week of cycle 1, escalated to 28 μg/day starting from Week 2 and all cycles thereafter. |
|
|
| Units | Counts |
|---|
| Participants |
|
|
|
|
Participants received blinatumomab by CIV over 4 weeks followed by a treatment-free interval of 2 weeks for up to 5 consecutive cycles. 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.
| OG002 | Phase 2: Blinatumomab 9/28 μg/Day (Adults) | Participants received blinatumomab by continuous intravenous infusion over 4 weeks followed by a treatment-free interval of 2 weeks for up to 5 consecutive cycles. The initial dose was 9 μg/day for the first week of cycle 1, escalated to 28 μg/day starting from Week 2 and all cycles thereafter. |
|
|
| OG002 | Blinatumomab 9/28 μg/Day (Phase 1b Only Adults) | 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 was 9 μg/day for the first week of cycle 1, escalated to 28 μg/day starting from week 2 and all cycles thereafter. |
| OG003 | Blinatumomab 5/15 µg/m²/Day (Phase 1b Only Pediatric) | Participants received blinatumomab by CIV over 4 weeks followed by a treatment-free interval of 2 weeks for up to 5 consecutive cycles. 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. |
|
|
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 was 9 μg/day for the first week of cycle 1, escalated to 28 μg/day starting from week 2 and all cycles thereafter. |
| OG003 | Blinatumomab 5/15 µg/m²/Day (Phase 1b Only Pediatric) | Participants received blinatumomab by CIV over 4 weeks followed by a treatment-free interval of 2 weeks for up to 5 consecutive cycles. 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. |
|
|
| OG003 | Blinatumomab 5/15 µg/m²/Day (Phase 1b Only Pediatric) | Participants received blinatumomab by CIV over 4 weeks followed by a treatment-free interval of 2 weeks for up to 5 consecutive cycles. 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. |
|
|
| OG003 | Blinatumomab 5/15 µg/m²/Day (Phase 1b Only Pediatric) | Participants received blinatumomab by CIV over 4 weeks followed by a treatment-free interval of 2 weeks for up to 5 consecutive cycles. 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. |
|
|
|
|
Participants received blinatumomab by CIV over 4 weeks followed by a treatment-free interval of 2 weeks for up to 5 consecutive cycles. 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. |
|
|
Participants received blinatumomab by CIV over 4 weeks followed by a treatment-free interval of 2 weeks for up to 5 consecutive cycles. 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. |
|
|
Participants received blinatumomab by CIV over 4 weeks followed by a treatment-free interval of 2 weeks for up to 5 consecutive cycles. 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. |
|
|
Participants received blinatumomab by CIV over 4 weeks followed by a treatment-free interval of 2 weeks for up to 5 consecutive cycles. 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. |
|
|
Participants received blinatumomab by CIV over 4 weeks followed by a treatment-free interval of 2 weeks for up to 5 consecutive cycles. 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. |
|
|
Participants received blinatumomab by CIV over 4 weeks followed by a treatment-free interval of 2 weeks for up to 5 consecutive cycles. 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.
|
|
| Participants |
|
|
|
| Title | Measurements |
|---|---|
|
| Title | Measurements |
|---|---|
|
| Title | Measurements |
|---|---|
|