| Primary | Overall Survival (OS) | OS was defined as the time from the date of randomization to the date of death due to any cause. Participants who were still alive or lost to follow up were censored at the time they were last known to be alive. Kaplan-Meier (KM) estimates was used for analysis. | | Posted | | Median | 95% Confidence Interval | months | | From the date of randomization up to the date of death (up to approximatley 74 months) | | | | ID | Title | Description |
|---|
| OG000 | Gilteritinib | Participants received 120 mg gilteritinib (3 tablets of 40 mg) orally, once a day in continuous 28-day cycles until treatment discontinuation criteria were met. Participants who met the treatment discontinuation criteria, entered the long-term follow-up period. Participants remained in the long-term follow-up period for up to 3 years from the participant's end of treatment visit or until discontinuation from the study. | | OG001 | Salvage Chemotherapy | Participants received salvage chemotherapy in continuous 28-day cycles per institutional guidelines. Salvage chemotherapy included: LoDAC: 20 mg cytarabine administered twice daily by SC/IV injection for 10 days. MEC: mitoxantrone 6 mg/m^2 per day administered by IV for 5 days (days 1 through 5), etoposide 100 mg/m^2 per day administered by IV for 5 days (days 1 through 5), cytarabine 1000 mg/m^2 per day administered by IV for 5 days (days 1 through 5). FLAG: G-CSF 300 μg/m^2 per day administered by SC/IV for 5 days (days 1 through 5), fludarabine 30 mg/m^2 per day administered by IV for 5 days (days 2 through 6), cytarabine 2000 mg/m^2 per day administered by IV for 5 days (days 2 through 6). Participants who met treatment discontinuation criteria, entered long-term follow-up and remained in the period for up to 3 years from the participant's end of treatment visit/until discontinuation from study. Based on the outcome of interim analysis, at investigators discretion, participants in the treatment period had the option to enter COE period to receive 120 mg gilteritinib, orally, once a day in continuous 28-day cycles until treatment discontinuation criteria was met. |
| | | Title | Denominators | Categories |
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| | | Title | Measurements |
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| - OG00010.3(8.8 to 12.7)
- OG0015.4(4.1 to 8.1)
|
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| | Group IDs | Group Description | Statistical Method | Statistical Comment | P-Value | P-Value Comment | Parameter Type | Parameter Value | Dispersion Type | Dispersion Value | Confidence Interval Sides | Confidence Interval % | CI Lower Limit | CI Upper Limit | CI Lower Limit Comment | CI Upper Limit Comment | Estimate Comment | Tested Non-Inferiority | Non-Inferiority Type | Non-Inferiority Comment | Other Analysis Description |
|---|
| | Log Rank | Stratification factors were response to first-line AML therapy and preselected salvage chemotherapy per interactive response technology (IRT). | 0.00152 | | Hazard Ratio (HR) | 0.612 | | | 2-Sided | 95 | 0.451 | 0.832 | | | Based on Cox proportional hazard model. Assuming proportional hazards, an HR < 1 indicates a reduction in hazard rate where the numerator is the Gilteritinib arm and the denominator is the Salvage chemotherapy arm. | | Superiority | | |
|
| Secondary | Event-Free Survival (EFS) | EFS: time from the date of randomization until the date of documented relapse, treatment failure, death, reported off treatment relapse or new AML therapy start whichever occued first, including the long-term follow-up data. KM estimate was used for analysis. Relapse was defined as documentation of any of following events:
- Bone marrow (BM) blasts ≥ 5% (not attributable to regenerating BM)
- Reappearance or new appearance of extramedullary leukemia
- Reappearance of significant numbers of peripheral blasts
Treatment failure: Treatment failure was defined as participant who ends treatment without having a previous response of CR, CR with incomplete platelet recovery (CRp) and CR with incomplete hematological recover (CRi). | | Posted | | Median | 95% Confidence Interval | months | | From the date of randomization up to the date of documented relapse, treatment failure or death from any cause, off-treatment relapse and start of new AML therapy (up to approximately 74 months) | | | | ID | Title | Description |
|---|
| OG000 | Gilteritinib | Participants received 120 mg gilteritinib (3 tablets of 40 mg) orally, once a day in continuous 28-day cycles until treatment discontinuation criteria were met. Participants who met the treatment discontinuation criteria, entered the long-term follow-up period. Participants remained in the long-term follow-up period for up to 3 years from the participant's end of treatment visit or until discontinuation from the study. | | OG001 | Salvage Chemotherapy | |
|
| Secondary | Complete Remission (CR) Rate | Percentage of participants with CR were reported. CR: morphologically leukemia-free state, with absolute neutrophil count (ANC) > 1x10^9 per liter (1x10^9/L), platelet count ≥ 100x10^9/L and normal marrow differential with <5% blasts. They were red blood cell (RBC) and platelet transfusion independent and no evidence of extramedullary leukemia or Auer rods was necessary. | | Posted | | Number | 95% Confidence Interval | Percentage of participants | | From the date of randomization up to approximately 74 months | | | | ID | Title | Description |
|---|
| OG000 | Gilteritinib | Participants received 120 mg gilteritinib (3 tablets of 40 mg) orally, once a day in continuous 28-day cycles until treatment discontinuation criteria were met. Participants who met the treatment discontinuation criteria, entered the long-term follow-up period. Participants remained in the long-term follow-up period for up to 3 years from the participant's end of treatment visit or until discontinuation from the study. | | OG001 | Salvage Chemotherapy | Participants received salvage chemotherapy in continuous 28-day cycles per institutional guidelines. Salvage chemotherapy included: LoDAC: 20 mg cytarabine administered twice daily by SC/IV injection for 10 days. MEC: mitoxantrone 6 mg/m^2 per day administered by IV for 5 days (days 1 through 5), etoposide 100 mg/m^2 per day administered by IV for 5 days (days 1 through 5), cytarabine 1000 mg/m^2 per day administered by IV for 5 days (days 1 through 5). FLAG: G-CSF 300 μg/m^2 per day administered by SC/IV for 5 days (days 1 through 5), fludarabine 30 mg/m^2 per day administered by IV for 5 days (days 2 through 6), cytarabine 2000 mg/m^2 per day administered by IV for 5 days (days 2 through 6). Participants who met treatment discontinuation criteria, entered long-term follow-up and remained in the period for up to 3 years from the participant's end of treatment visit/until discontinuation from study. Based on the outcome of interim analysis, at investigators discretion, participants in the treatment period had the option to enter COE period to receive 120 mg gilteritinib, orally, once a day in continuous 28-day cycles until treatment discontinuation criteria was met. |
|
| Secondary | Duration of CR | Duration of CR: time from the date of achieving first CR until date of first documented relapse for participants who achieved CR. KM estimate was used for analysis. CR: morphologically leukemia-free state, with ANC> 1x10^9/L, platelet count ≥ 100x10^9/L and normal marrow differential with < 5% blasts. They were RBC and platelet transfusion independent and no evidence of extramedullary leukemia. Relapse was defined as documentation of any of following events:
- BM blasts ≥ 5% (not attributable to regenerating BM)
- Reappearance or new appearance of extramedullary leukemia
- Reappearance of significant numbers of peripheral blasts
| ITT. Participants with CR were analyzed. | Posted | | Median | 95% Confidence Interval | months | | From date of achieving CR until date of confirmed relapse (maximum duration was 53.4 months ) | | | | ID | Title | Description |
|---|
| OG000 | Gilteritinib | Participants received 120 mg gilteritinib (3 tablets of 40 mg) orally, once a day in continuous 28-day cycles until treatment discontinuation criteria were met. Participants who met the treatment discontinuation criteria, entered the long-term follow-up period. Participants remained in the long-term follow-up period for up to 3 years from the participant's end of treatment visit or until discontinuation from the study. | | OG001 | Salvage Chemotherapy | Participants received salvage chemotherapy in continuous 28-day cycles per institutional guidelines. Salvage chemotherapy included: LoDAC: 20 mg cytarabine administered twice daily by SC/IV injection for 10 days. MEC: mitoxantrone 6 mg/m^2 per day administered by IV for 5 days (days 1 through 5), etoposide 100 mg/m^2 per day administered by IV for 5 days (days 1 through 5), cytarabine 1000 mg/m^2 per day administered by IV for 5 days (days 1 through 5). FLAG: G-CSF 300 μg/m^2 per day administered by SC/IV for 5 days (days 1 through 5), fludarabine 30 mg/m^2 per day administered by IV for 5 days (days 2 through 6), cytarabine 2000 mg/m^2 per day administered by IV for 5 days (days 2 through 6). Participants who met treatment discontinuation criteria, entered long-term follow-up and remained in the period for up to 3 years from the participant's end of treatment visit/until discontinuation from study. Based on the outcome of interim analysis, at investigators discretion, participants in the treatment period had the option to enter COE period to receive 120 mg gilteritinib, orally, once a day in continuous 28-day cycles until treatment discontinuation criteria was met. |
|
| Secondary | Duration of Composite Complete Remission (CRc) | Duration of CRc: time from date of achieving first CRc until date of first documented relapse for participants who achieved CRc. KM estimate was used for analysis. CRc: rate of all complete & incomplete remissions [CR + CRp + CRi]. CR: morphologically leukemia-free state, with ANC> 1x10^9/L, platelet count ≥ 100x10^9/L and normal marrow differential with <5% blasts. They were RBC and platelet transfusion independent and no evidence of extramedullary leukemia. CRp: met all CR criteria except incomplete platelet recovery (< 100x10^9/L). CRi: met all CR criteria, except for incomplete hematological recovery with residual neutropenia < 1x10^9/L with or without complete platelet recovery. Relapse: BM blasts ≥ 5%, reappearance or new appearance of extramedullary leukemia, reappearance of significant numbers of peripheral blasts. | ITT. Participants with best overall response of CRc were analyzed. | Posted | | Median | 95% Confidence Interval | months | | From date of achieving CRc until date of confirmed relapse (maximum duration was 60 months) | | | | ID | Title | Description |
|---|
| OG000 | Gilteritinib | Participants received 120 mg gilteritinib (3 tablets of 40 mg) orally, once a day in continuous 28-day cycles until treatment discontinuation criteria were met. Participants who met the treatment discontinuation criteria, entered the long-term follow-up period. Participants remained in the long-term follow-up period for up to 3 years from the participant's end of treatment visit or until discontinuation from the study. | | OG001 |
|
| Secondary | Duration of CR/Complete Remission With Partial Hematologic Recovery (CRh) | Duration of CR/CRh: time from date of achieving first CR/CRh until date of first documented relapse for participants who achieved CR/CRh. KM estimate was used for analysis. CR: morphologically leukemia-free state, with ANC> 1x10^9/L, platelet count ≥ 100x10^9/L and normal marrow differential with <5% blasts. They were RBC and platelet transfusion independent and no evidence of extramedullary leukemia. CRh was defined as a condition at the post baseline visit, having bone marrow blasts < 5%, partial hematologic recovery ANC ≥ 0.5x10^9/L and platelets ≥ 50x10^9/L, no evidence of extramedullary leukemia and cannot be classified as CR. The blast counts in peripheral blood was ≤ 2%. Relapse: BM blasts ≥ 5%, reappearance or new appearance of extramedullary leukemia, reappearance of significant numbers of peripheral blasts. | ITT. Participants with CR/CRh were analyzed. | Posted | | Median | 95% Confidence Interval | months | | From date of achieving CR/CRh until date of confirmed relapse (maximum duration was 58.1 months) | | | | ID | Title | Description |
|---|
| OG000 | Gilteritinib | Participants received 120 mg gilteritinib (3 tablets of 40 mg) orally, once a day in continuous 28-day cycles until treatment discontinuation criteria were met. Participants who met the treatment discontinuation criteria, entered the long-term follow-up period. Participants remained in the long-term follow-up period for up to 3 years from the participant's end of treatment visit or until discontinuation from the study. | | OG001 |
|
| Secondary | Duration Of Response (DOR) | DOR: time from date of first CRc (CR+CRp+CRi)/PR until date of first documented relapse for participants who achieved CRc or PR. KM estimate used for analysis. CR: morphologically leukemia-free state, with ANC> 1x10^9/L, platelet count ≥ 100x10^9/L and normal marrow differential with <5% blasts. They were RBC and platelet transfusion independent and no evidence of extramedullary leukemia. CRp: met all CR criteria except incomplete platelet recovery (< 100x10^9/L). CRi: met all CR criteria, except for incomplete hematological recovery with residual neutropenia < 1x10^9/L with or without complete platelet recovery. PR: condition with regeneration of normal hematopoietic cells in BM, no detectable blasts, ≥ 50% decrease of blasts in BM aspirate & total BM blasts of 5-25%. Relapse: BM blasts ≥ 5%, reappearance or new appearance of extramedullary leukemia, reappearance of significant numbers of peripheral blasts and increase in the percentage of blasts in the BM aspirate to > 25%. | ITT. Participants with best overall response of CRc/PR were analyzed. | Posted | | Median | 95% Confidence Interval | months | | From date of achieving CRc/PR until date of confirmed relapse (maximum duration was 52.1 months) | | | | ID | Title | Description |
|---|
| OG000 | Gilteritinib | Participants received 120 mg gilteritinib (3 tablets of 40 mg) orally, once a day in continuous 28-day cycles until treatment discontinuation criteria were met. Participants who met the treatment discontinuation criteria, entered the long-term follow-up period. Participants remained in the long-term follow-up period for up to 3 years from the participant's end of treatment visit or until discontinuation from the study. |
|
| Secondary | CR/CRh Rate | Percentage of participants with CR/CRh was reported. CR: morphologically leukemia-free state, with ANC> 1x10^9/L, platelet count ≥ 100x10^9/L and normal marrow differential with <5% blasts. They were RBC and platelet transfusion independent and no evidence of extramedullary leukemia. CRh was defined as a condition at the post baseline visit, having bone marrow blasts < 5%, partial hematologic recovery ANC ≥ 0.5x10^9/L and platelets ≥ 50x10^9/L, no evidence of extramedullary leukemia and could be classified as CR. The blast counts in peripheral blood was ≤ 2%. | | Posted | | Number | 95% Confidence Interval | Percentage of participants | | From the date of randomization up to approximately 74 months | | | | ID | Title | Description |
|---|
| OG000 | Gilteritinib | Participants received 120 mg gilteritinib (3 tablets of 40 mg) orally, once a day in continuous 28-day cycles until treatment discontinuation criteria were met. Participants who met the treatment discontinuation criteria, entered the long-term follow-up period. Participants remained in the long-term follow-up period for up to 3 years from the participant's end of treatment visit or until discontinuation from the study. | | OG001 | Salvage Chemotherapy | Participants received salvage chemotherapy in continuous 28-day cycles per institutional guidelines. Salvage chemotherapy included: LoDAC: 20 mg cytarabine administered twice daily by SC/IV injection for 10 days. MEC: mitoxantrone 6 mg/m^2 per day administered by IV for 5 days (days 1 through 5), etoposide 100 mg/m^2 per day administered by IV for 5 days (days 1 through 5), cytarabine 1000 mg/m^2 per day administered by IV for 5 days (days 1 through 5). FLAG: G-CSF 300 μg/m^2 per day administered by SC/IV for 5 days (days 1 through 5), fludarabine 30 mg/m^2 per day administered by IV for 5 days (days 2 through 6), cytarabine 2000 mg/m^2 per day administered by IV for 5 days (days 2 through 6). Participants who met treatment discontinuation criteria, entered long-term follow-up and remained in the period for up to 3 years from the participant's end of treatment visit/until discontinuation from study. Based on the outcome of interim analysis, at investigators discretion, participants in the treatment period had the option to enter COE period to receive 120 mg gilteritinib, orally, once a day in continuous 28-day cycles until treatment discontinuation criteria was met. |
|
| Secondary | Best Response Rate | Defined as percentage of participants with CR, CRp, CRi, PR, no response (NR) & not estimable (NE). CR: morphologically leukemia-free state, with ANC> 1x10^9/L, platelet count ≥ 100x10^9/L & normal marrow differential with < 5% blasts. They were RBC & platelet transfusion independent & no evidence of extramedullary leukemia. CRp: met all CR criteria except incomplete platelet recovery (<100x10^9/L). CRi: met all CR criteria, except incomplete hematological recovery with residual neutropenia < 1x10^9/L with/without complete platelet recovery. PR: condition with regeneration of normal hematopoietic cells in BM, no detectable blasts, ≥ 50% decrease of blasts in BM aspirate & total BM blasts of 5-25%. <=5% BM blasts if Auer rods are present, no evidence of extramedullary leukemia. Not Estimable (NE): No BM assessed/no myeloblast value, no blast value from peripheral blood or ≤2%, & no extramedullary leukemia. No Response (NR): Response not categorized as CR, CRp, CRi, PR or NE. | | Posted | | Number | | Percentage of participants | | From the date of randomization up to approximately 74 months | | | | ID | Title | Description |
|---|
| OG000 | Gilteritinib | Participants received 120 mg gilteritinib (3 tablets of 40 mg) orally, once a day in continuous 28-day cycles until treatment discontinuation criteria were met. Participants who met the treatment discontinuation criteria, entered the long-term follow-up period. Participants remained in the long-term follow-up period for up to 3 years from the participant's end of treatment visit or until discontinuation from the study. | | OG001 |
|
| Secondary | Leukemia-Fee Survival (LFS) | LFS: time from the date of first CRc (CR+CRp+CRi) until the date of documented relapse or death for participants who achieved CRc. CR: morphologically leukemia-free state, with ANC> 1x10^9/L, platelet count ≥ 100x10^9/L and normal marrow differential with < 5% blasts. They were RBC and platelet transfusion independent and no evidence of extramedullary leukemia. CRp: met all CR criteria except incomplete platelet recovery (< 100x10^9/L). CRi: met all CR criteria, except for incomplete hematological recovery with residual neutropenia < 1x10^9/L with or without complete platelet recovery. Relapse: BM blasts ≥ 5%, reappearance or new appearance of extramedullary leukemia, reappearance of significant numbers of peripheral blasts. | ITT. Participants with best overall response of CRc were analyzed. | Posted | | Median | 95% Confidence Interval | months | | From first day of achieving first CRc to the first day of confirmed relapse/death (maximum duration was 60.0 months) | | | | ID | Title | Description |
|---|
| OG000 | Gilteritinib | Participants received 120 mg gilteritinib (3 tablets of 40 mg) orally, once a day in continuous 28-day cycles until treatment discontinuation criteria were met. Participants who met the treatment discontinuation criteria, entered the long-term follow-up period. Participants remained in the long-term follow-up period for up to 3 years from the participant's end of treatment visit or until discontinuation from the study. | | OG001 | Salvage Chemotherapy | |
|
| Secondary | Composite Complete Remission (CRc) | Percentage of participants with CRc (CR+CRp+CRi) was reported. CR: morphologically leukemia-free state, with ANC> 1x10^9/L, platelet count ≥ 100x10^9/L and normal marrow differential with <5% blasts. They were RBC and platelet transfusion independent and no evidence of extramedullary leukemia. CRp: met all CR criteria except incomplete platelet recovery (< 100x10^9/L). CRi: met all CR criteria, except for incomplete hematological recovery with residual neutropenia < 1x10^9/L with or without complete platelet recovery. | | Posted | | Number | 95% Confidence Interval | Percentage of participants | | From the date of randomization up to approximately 74 months | | | | ID | Title | Description |
|---|
| OG000 | Gilteritinib | Participants received 120 mg gilteritinib (3 tablets of 40 mg) orally, once a day in continuous 28-day cycles until treatment discontinuation criteria were met. Participants who met the treatment discontinuation criteria, entered the long-term follow-up period. Participants remained in the long-term follow-up period for up to 3 years from the participant's end of treatment visit or until discontinuation from the study. | | OG001 | Salvage Chemotherapy | PParticipants received salvage chemotherapy in continuous 28-day cycles per institutional guidelines. Salvage chemotherapy included: Low dose cytarabine (LoDAC): 20 mg cytarabine administered twice daily by subcutaneous (SC)/intravenous (IV) injection for 10 days. Mitoxantrone, etoposide and intermediate dose cytarabine (MEC): mitoxantrone 6 milligrams per square meter(mg/m^2) per day administered by IV for 5 days (days 1 through 5), etoposide 100 mg/m^2 per day administered by IV for 5 days (days 1 through 5), cytarabine 1000 mg/m^2 per day administered by IV for 5 days (days 1 through 5). Fludarabine, cytarabine and granulocyte colony-stimulating factor (FLAG): granulocyte colony-stimulating factor (G-CSF) 300 micrograms per square meter (μg/m^2) per day administered by SC/IV for 5 days (days 1 through 5), fludarabine 30 mg/m^2 per day administered by IV for 5 days (days 2 through 6), cytarabine 2000 mg/m^2 per day administered by IV for 5 days (days 2 through 6). Participants who met treatment discontinuation criteria, entered long-term follow-up and remained in the period for up to 3 years from the participant's end of treatment visit/until discontinuation from study. Based on the outcome of interim analysis, at investigators discretion, participants in the treatment period had the option to enter crossover extension (COE) period to receive 120 mg gilteritinib, orally, once a day in continuous 28-day cycles until treatment discontinuation criteria was met. |
|
| Secondary | Time to CRc | Time to CRc (TTCRc) was defined as the time from the date of randomization until the date of first CRc. CRc: Rate of all complete and incomplete remissions (CR + CRp +Cri) CR: morphologically leukemia-free state, with ANC> 1x10^9/L, platelet count ≥ 100x10^9/L and normal marrow differential with <5% blasts. They were RBC and platelet transfusion independent and no evidence of extramedullary leukemia. CRp: met all CR criteria except incomplete platelet recovery (< 100x10^9/L). CRi: met all CR criteria, except for incomplete hematological recovery with residual neutropenia < 1x10^9/L with or without complete platelet recovery. | ITT population. Participants who achieved CRc were analyzed. | Posted | | Median | Full Range | months | | From randomization until date of first CRc (up to approximately 74 months) | | | | ID | Title | Description |
|---|
| OG000 | Gilteritinib | Participants received 120 milligrams (mg) gilteritinib (3 tablets of 40 mg) orally, once a day in continuous 28-day cycles until treatment discontinuation criteria were met. Participants who met the treatment discontinuation criteria, entered the long-term follow-up period. Participants received 120 mg gilteritinib (3 tablets of 40 mg) orally, once a day in continuous 28-day cycles until treatment discontinuation criteria were met. Participants who met the treatment discontinuation criteria, entered the long-term follow-up period. Participants remained in the long-term follow-up period for up to 3 years from the participant's end of treatment visit or until discontinuation from the study. | | OG001 |
|
| Secondary | Time to CR | Time to CR (TTCR) was defined as the time from the date of randomization until the date of first CR. CR: morphologically leukemia-free state, with ANC> 1x10^9/L, platelet count ≥ 100x10^9/L and normal marrow differential with < 5% blasts. They were RBC and platelet transfusion independent and no evidence of extramedullary leukemia. | ITT population. Participants who achieved CR were analyzed. | Posted | | Median | Full Range | months | | From randomization until date of first CR (up to approximately 74 months) | | | | ID | Title | Description |
|---|
| OG000 | Gilteritinib | Participants received 120 mg gilteritinib (3 tablets of 40 mg) orally, once a day in continuous 28-day cycles until treatment discontinuation criteria were met. Participants who met the treatment discontinuation criteria, entered the long-term follow-up period. Participants remained in the long-term follow-up period for up to 3 years from the participant's end of treatment visit or until discontinuation from the study. | | OG001 | Salvage Chemotherapy | Participants received salvage chemotherapy in continuous 28-day cycles per institutional guidelines. Salvage chemotherapy included: LoDAC: 20 mg cytarabine administered twice daily by SC/IV injection for 10 days. MEC: mitoxantrone 6 mg/m^2 per day administered by IV for 5 days (days 1 through 5), etoposide 100 mg/m^2 per day administered by IV for 5 days (days 1 through 5), cytarabine 1000 mg/m^2 per day administered by IV for 5 days (days 1 through 5). FLAG: G-CSF 300 μg/m^2 per day administered by SC/IV for 5 days (days 1 through 5), fludarabine 30 mg/m^2 per day administered by IV for 5 days (days 2 through 6), cytarabine 2000 mg/m^2 per day administered by IV for 5 days (days 2 through 6). Participants who met treatment discontinuation criteria, entered long-term follow-up and remained in the period for up to 3 years from the participant's end of treatment visit/until discontinuation from study. Based on the outcome of interim analysis, at investigators discretion, participants in the treatment period had the option to enter COE period to receive 120 mg gilteritinib, orally, once a day in continuous 28-day cycles until treatment discontinuation criteria was met. |
|
| Secondary | Time to Response | Time to Response (TTR) was defined as the time from the date of randomization until the date of either first response (CRc or PR). CRc: Rate of all complete and incomplete remissions (CR + CRp +Cri) CR: morphologically leukemia-free state, with ANC> 1x10^9/L, platelet count ≥ 100x10^9/L and normal marrow differential with <5% blasts. They were RBC and platelet transfusion independent and no evidence of extramedullary leukemia. CRp: met all CR criteria except incomplete platelet recovery (< 100x10^9/L). CRi: met all CR criteria, except for incomplete hematological recovery with residual neutropenia < 1x10^9/L with or without complete platelet recovery. PR: condition with regeneration of normal hematopoietic cells in BM, no detectable blasts, ≥ 50% decrease of blasts in BM aspirate & total BM blasts of 5-25%. | ITT population. Participants who achieved CRc or PR were analyzed. | Posted | | Median | Full Range | months | | From randomization until date of first CRc or PR (up to approximately 74 months) | | | | ID | Title | Description |
|---|
| OG000 | Gilteritinib | Participants received 120 mg gilteritinib (3 tablets of 40 mg) orally, once a day in continuous 28-day cycles until treatment discontinuation criteria were met. Participants who met the treatment discontinuation criteria, entered the long-term follow-up period. Participants remained in the long-term follow-up period for up to 3 years from the participant's end of treatment visit or until discontinuation from the study. | | OG001 | Salvage Chemotherapy |
|
| Secondary | Time to CR/CRh | Time to CR/CRh (TTCRCRh) was defined as the time from the date of randomization until the date of first CR/CRh. CR: morphologically leukemia-free state, with ANC> 1x10^9/L, platelet count ≥ 100x10^9/L and normal marrow differential with <5% blasts. They were RBC and platelet transfusion independent and no evidence of extramedullary leukemia. CRh was defined as a condition at the post baseline visit, having bone marrow blasts < 5%, partial hematologic recovery ANC ≥ 0.5x10^9/L and platelets ≥ 50x10^9/L, no evidence of extramedullary leukemia and cannot be classified as CR. The blast counts in peripheral blood was ≤ 2%. | ITT population. Participants who achieved CR/CRh were analyzed. | Posted | | Median | Full Range | months | | From randomization until date of first CR/CRh (up to approximately 74 months) | | | | ID | Title | Description |
|---|
| OG000 | Gilteritinib | Participants received 120 mg gilteritinib (3 tablets of 40 mg) orally, once a day in continuous 28-day cycles until treatment discontinuation criteria were met. Participants who met the treatment discontinuation criteria, entered the long-term follow-up period. Participants remained in the long-term follow-up period for up to 3 years from the participant's end of treatment visit or until discontinuation from the study. | | OG001 | Salvage Chemotherapy | Participants received salvage chemotherapy in continuous 28-day cycles per institutional guidelines. Salvage chemotherapy included: LoDAC: 20 mg cytarabine administered twice daily by SC/IV injection for 10 days. MEC: mitoxantrone 6 mg/m^2 per day administered by IV for 5 days (days 1 through 5), etoposide 100 mg/m^2 per day administered by IV for 5 days (days 1 through 5), cytarabine 1000 mg/m^2 per day administered by IV for 5 days (days 1 through 5). FLAG: G-CSF 300 μg/m^2 per day administered by SC/IV for 5 days (days 1 through 5), fludarabine 30 mg/m^2 per day administered by IV for 5 days (days 2 through 6), cytarabine 2000 mg/m^2 per day administered by IV for 5 days (days 2 through 6). Participants who met treatment discontinuation criteria, entered long-term follow-up and remained in the period for up to 3 years from the participant's end of treatment visit/until discontinuation from study. Based on the outcome of interim analysis, at investigators discretion, participants in the treatment period had the option to enter COE period to receive 120 mg gilteritinib, orally, once a day in continuous 28-day cycles until treatment discontinuation criteria was met. |
|
| Secondary | Percentage of Participants With Transfusion Conversion and Transfusion Maintenance | Transfusion conversion rate: Percentage of transfusion dependent participants at baseline period but became transfusion independent at post-baseline period divided by total participants who were transfusion dependent at baseline period. Transfusion maintenance rate: Percentage of transfusion independent participants at baseline period and still maintained transfusion independent at post-baseline period divided by total participants who were transfusion independent at baseline period. Baseline transfusion status: Participants were classified as transfusion independent if there were no RBC or platelet transfusions within 28 days prior to first dose to 28 days after first dose; otherwise classified as transfusion dependent. Post baseline transfusion status: Participants on treatment ≥ 84 days were classified as transfusion independent, if consecutive 56 days without any RBC or platelet transfusion; otherwise classified as transfusion dependent | ITT population with available data at specified timepoint. This endpoint was planned to be analyzed only for Giltertinib arm. | Posted | | Number | | Percentage of participants | | Baseline up to approximately 74 months | | | | ID | Title | Description |
|---|
| OG000 | Gilteritinib | Participants received 120 mg gilteritinib (3 tablets of 40 mg) orally, once a day in continuous 28-day cycles until treatment discontinuation criteria were met. Participants who met the treatment discontinuation criteria, entered the long-term follow-up period. Participants remained in the long-term follow-up period for up to 3 years from the participant's end of treatment visit or until discontinuation from the study. |
|
| Secondary | Percentage of Participants With Transplantation Rate | Transplantation rate is defined as the percentage of participants undergoing Hematopoietic stem cell transplant (HSCT) during the study period. | | Posted | | Number | 95% Confidence Interval | Percentage of participants | | Baseline up to approximately 74 months | | | | ID | Title | Description |
|---|
| OG000 | Gilteritinib | Participants received 120 mg gilteritinib (3 tablets of 40 mg) orally, once a day in continuous 28-day cycles until treatment discontinuation criteria were met. Participants who met the treatment discontinuation criteria, entered the long-term follow-up period. Participants remained in the long-term follow-up period for up to 3 years from the participant's end of treatment visit or until discontinuation from the study. | | OG001 | Salvage Chemotherapy | Participants received salvage chemotherapy in continuous 28-day cycles per institutional guidelines. Salvage chemotherapy included: LoDAC: 20 mg cytarabine administered twice daily by SC/IV injection for 10 days. MEC: mitoxantrone 6 mg/m^2 per day administered by IV for 5 days (days 1 through 5), etoposide 100 mg/m^2 per day administered by IV for 5 days (days 1 through 5), cytarabine 1000 mg/m^2 per day administered by IV for 5 days (days 1 through 5). FLAG: G-CSF 300 μg/m^2 per day administered by SC/IV for 5 days (days 1 through 5), fludarabine 30 mg/m^2 per day administered by IV for 5 days (days 2 through 6), cytarabine 2000 mg/m^2 per day administered by IV for 5 days (days 2 through 6). Participants who met treatment discontinuation criteria, entered long-term follow-up and remained in the period for up to 3 years from the participant's end of treatment visit/until discontinuation from study. Based on the outcome of interim analysis, at investigators discretion, participants in the treatment period had the option to enter COE period to receive 120 mg gilteritinib, orally, once a day in continuous 28-day cycles until treatment discontinuation criteria was met. |
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| Secondary | Change From Baseline in Brief Fatigue Inventory (BFI) | The BFI is a screening tool designed to assess the severity and impact of fatigue on daily functioning of participants with cancer during the 24 hours. There are 9 items on the scale. The first three questions ask participants to rate their fatigues on a scale from 0 (no fatigue) - 10 (as bad as you can imagine), with higher scores indicating worse outcome. The remaining six questions ask participants to rate how much fatigue has interfered with their daily activities on a scale from 0 (Does not interfere) to 10 (Completely interferes). A global fatigue score can be obtained by averaging all the items on the BFI, ranging between 0 to 10; a higher BFI fatigue score indicates worse outcome. The global BFI scores were calculated only if at least 5 of the 9 items are answered. | ITT population with data available at specified timepoint. | Posted | | Mean | Standard Deviation | Scores on scale | | Baseline, End of treatment (63 months) | | | | ID | Title | Description |
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| OG000 | Gilteritinib | Participants received 120 mg gilteritinib (3 tablets of 40 mg) orally, once a day in continuous 28-day cycles until treatment discontinuation criteria were met. Participants who met the treatment discontinuation criteria, entered the long-term follow-up period. Participants remained in the long-term follow-up period for up to 3 years from the participant's end of treatment visit or until discontinuation from the study. | | OG001 | Salvage Chemotherapy | |
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| Secondary | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | An AE was defined as any untoward medical occurrence in a participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE could therefore be any unfavorable & unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. TEAE was defined as an adverse event observed after starting administration of the study drug. | Safety Analysis Set (SAF): The SAF consisted of all participants who received at least 1 dose of study treatment (gilteritinib or salvage chemotherapy). | Posted | | Number | | Participants | | From the date of first dose up to approximately 74 months | | | | ID | Title | Description |
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| OG000 | Gilteritinib | Participants received 120 mg gilteritinib (3 tablets of 40 mg) orally, once a day in continuous 28-day cycles until treatment discontinuation criteria were met. Participants who met the treatment discontinuation criteria, entered the long-term follow-up period. Participants remained in the long-term follow-up period for up to 3 years from the participant's end of treatment visit or until discontinuation from the study. | | OG001 | Salvage Chemotherapy | Participants received salvage chemotherapy in continuous 28-day cycles per institutional guidelines. Salvage chemotherapy included: LoDAC: 20 mg cytarabine administered twice daily by SC/IV injection for 10 days. MEC: mitoxantrone 6 mg/m^2 per day administered by IV for 5 days (days 1 through 5), etoposide 100 mg/m^2 per day administered by IV for 5 days (days 1 through 5), cytarabine 1000 mg/m^2 per day administered by IV for 5 days (days 1 through 5). FLAG: G-CSF 300 μg/m^2 per day administered by SC/IV for 5 days (days 1 through 5), fludarabine 30 mg/m^2 per day administered by IV for 5 days (days 2 through 6), cytarabine 2000 mg/m^2 per day administered by IV for 5 days (days 2 through 6). Participants who met treatment discontinuation criteria, entered long-term follow-up and remained in the period for up to 3 years from the participant's end of treatment visit/until discontinuation from study. Based on the outcome of interim analysis, at investigators discretion, participants in the treatment period had the option to enter COE period to receive 120 mg gilteritinib, orally, once a day in continuous 28-day cycles until treatment discontinuation criteria was met. |
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| Secondary | Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Scores | The ECOG Scale was used to assess performance status. Number of participants with each grade was reported. Grade Description: 0: Fully active, able to carry on all pre-disease performance without restriction.
- Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light house work, office work.
- Ambulatory and capable of all self-care but unable to carry out any work activities. Up and about more than 50% of waking hours.
- Capable of only limited self-care, confined to bed or chair more than 50% of waking hours.
- Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair.
- Dead.
| SAF population with available data at specified timepoint. | Posted | | Number | | Participants | | Baseline, end of treatment visit (63 months) | | | | ID | Title | Description |
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| OG000 | Gilteritinib | Participants received 120 mg gilteritinib (3 tablets of 40 mg) orally, once a day in continuous 28-day cycles until treatment discontinuation criteria were met. Participants who met the treatment discontinuation criteria, entered the long-term follow-up period. Participants remained in the long-term follow-up period for up to 3 years from the participant's end of treatment visit or until discontinuation from the study. | | OG001 | Salvage Chemotherapy | Participants received salvage chemotherapy in continuous 28-day cycles per institutional guidelines. Salvage chemotherapy included: LoDAC: 20 mg cytarabine administered twice daily by SC/IV injection for 10 days. MEC: mitoxantrone 6 mg/m^2 per day administered by IV for 5 days (days 1 through 5), etoposide 100 mg/m^2 per day administered by IV for 5 days (days 1 through 5), cytarabine 1000 mg/m^2 per day administered by IV for 5 days (days 1 through 5). FLAG: G-CSF 300 μg/m^2 per day administered by SC/IV for 5 days (days 1 through 5), fludarabine 30 mg/m^2 per day administered by IV for 5 days (days 2 through 6), cytarabine 2000 mg/m^2 per day administered by IV for 5 days (days 2 through 6). Participants who met treatment discontinuation criteria, entered long-term follow-up and remained in the period for up to 3 years from the participant's end of treatment visit/until discontinuation from study. Based on the outcome of interim analysis, at investigators discretion, participants in the treatment period had the option to enter COE period to receive 120 mg gilteritinib, orally, once a day in continuous 28-day cycles until treatment discontinuation criteria was met. |
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| Secondary | Pharmacokinetics (PK) of Gilteritinib in Chinese PK Cohort: Area Under the Concentration Curve at 24 Hours (AUC24) | AUC24 was derived from the PK samples collected. | Pharmacokinetics Analysis Set (PKAS): The PKAS consisted of all participants who received at least 1 administration of study intervention for which at least 1 concentration data with time of dosing and sampling were available. This endpoint was planned to be analyzed only for participants in Giltertinib PK cohort which included 21 participants from six china sites. | Posted | | Mean | Standard Deviation | nanogram*hour per milliliters(ng*h/mL) | | Cycle 1 Day 1(C1D1): predose, 0.5, 1, 2, 3, 4, 6, 10, 24 hour post dose, Cycle 1 Day 15(C1D15): predose, 0.5, 1, 2, 3, 4, 6, 10, 24 hour post dose | | | | ID | Title | Description |
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| OG000 | Gilteritinib | Participants received 120 mg gilteritinib (3 tablets of 40 mg) orally, once a day in continuous 28-day cycles until treatment discontinuation criteria were met. Participants who met the treatment discontinuation criteria, entered the long-term follow-up period. Participants remained in the long-term follow-up period for up to 3 years from the participant's end of treatment visit or until discontinuation from the study. |
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| Secondary | PK of Gilteritinib in Chinese PK Cohort: Maximum Concentration (Cmax) | Cmax was derived from the PK samples collected. | PKAS. This endpoint was planned to be analysed only for participants in Giltertinib PK cohort which included 21 participants from six china sites. | Posted | | Mean | Standard Deviation | ng/mL | | C1D1: predose, 0.5, 1, 2, 3, 4, 6, 10, 24 hour post dose, C1D15: predose, 0.5, 1, 2, 3, 4, 6, 10, 24 hour post dose | | | | ID | Title | Description |
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| OG000 | Gilteritinib | Participants received 120 mg gilteritinib (3 tablets of 40 mg) orally, once a day in continuous 28-day cycles until treatment discontinuation criteria were met. Participants who met the treatment discontinuation criteria, entered the long-term follow-up period. Participants remained in the long-term follow-up period for up to 3 years from the participant's end of treatment visit or until discontinuation from the study. |
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| Secondary | PK of Gilteritinib: Observed Trough Concentration (Ctrough) | Ctrough was derived from the PK samples collected. | PKAS with available data at timepoint were analyzed. This endpoint was planned to be analyzed only for participants at the China site in the Giltertinib PK cohort. | Posted | | Mean | Standard Deviation | ng/mL | | Predose on C1D15 | | | | ID | Title | Description |
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| OG000 | Gilteritinib | Participants received 120 mg gilteritinib (3 tablets of 40 mg) orally, once a day in continuous 28-day cycles until treatment discontinuation criteria were met. Participants who met the treatment discontinuation criteria, entered the long-term follow-up period. Participants remained in the long-term follow-up period for up to 3 years from the participant's end of treatment visit or until discontinuation from the study. |
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| Secondary | PK of Gilteritinib in Chinese PK Cohort: Time to Maximum Concentration (Tmax) | tmax was derived from the PK samples collected. | PKAS. This endpoint was planned to be analysed only for participants in Giltertinib PK cohort which included 21 participants from six china sites. | Posted | | Median | Full Range | hours | | C1D1: predose, 0.5, 1, 2, 3, 4, 6, 10, 24 hours (+/- 20 minutes) post dose, C1D15: predose, 0.5, 1, 2, 3, 4, 6, 10, 24 hours (+/- 20 minutes) post dose | | | | ID | Title | Description |
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| OG000 | Gilteritinib | Participants received 120 mg gilteritinib (3 tablets of 40 mg) orally, once a day in continuous 28-day cycles until treatment discontinuation criteria were met. Participants who met the treatment discontinuation criteria, entered the long-term follow-up period. Participants remained in the long-term follow-up period for up to 3 years from the participant's end of treatment visit or until discontinuation from the study. |
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| Secondary | Ctrough Concentration of Gilteritinib | Concentrations below the lower limit of quantification (0.5 ng/mL) were set to zero. | PKAS with available data at timepoint were analyzed. This endpoint was planned to be analyzed only for participants at the China site in the Giltertinib PK cohort. | Posted | | Mean | Standard Deviation | ng/mL | | Predose C1D8, C1D15, Day 1 of each cycle from C2 to C65, C67D1,C68D1,C69D1,C70D1 | | | | ID | Title | Description |
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| OG000 | Gilteritinib | Participants received 120 mg gilteritinib (3 tablets of 40 mg) orally, once a day in continuous 28-day cycles until treatment discontinuation criteria were met. Participants who met the treatment discontinuation criteria, entered the long-term follow-up period. Participants remained in the long-term follow-up period for up to 3 years from the participant's end of treatment visit or until discontinuation from the study. |
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