A Study of ASP2215 Versus Salvage Chemotherapy in Patients With Relapsed or Refractory Acute Myeloid Leukemia (AML) With FMS-like Tyrosine Kinase (FLT3) Mutation
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ClinicalTrials.gov Identifier: NCT02421939 |
Recruitment Status :
Active, not recruiting
First Posted : April 21, 2015
Results First Posted : October 17, 2019
Last Update Posted : August 11, 2022
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Sponsor:
Astellas Pharma Global Development, Inc.
Information provided by (Responsible Party):
Astellas Pharma Inc ( Astellas Pharma Global Development, Inc. )
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Study Type | Interventional |
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Study Design | Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment |
Condition |
Leukemia, Acute Myeloid (AML) |
Interventions |
Drug: gilteritinib Drug: LoDAC (Low Dose Cytarabine) Drug: Azacitidine Drug: MEC (Mitoxantrone, Etoposide, Cytarabine) Drug: FLAG-IDA (Granulocyte-Colony Stimulating Factor (G-CSF), Fludarabine, Cytarabine, Idarubicin) |
Enrollment | 371 |
Participant Flow
Recruitment Details | Participants were recruited from approximately 140 centers in North America, Europe, Asia and the rest of the world and randomized in a 2:1 ratio to receive gilteritinib or salvage chemotherapy. Participants had FMS-like tyrosine kinase 3 (FLT3) mutations and relapsed or refractory acute myeloid leukemia (AML) after first-line therapy. |
Pre-assignment Details | Participants entered the screening period up to 14 days prior to the start of treatment. Prior to randomization, the investigator preselected a salvage chemotherapy for each participant. The randomization was stratified by response to first-line AML therapy and preselected salvage chemotherapy. Treatment was given over continuous 28-day cycles. |
Arm/Group Title | Gilteritinib | Salvage Chemotherapy |
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Participants received 120 mg dose (3 tablets of 40 mg) orally once a day in continuous 28-day cycles, at least 2 hours after or 1 hour before food. Gilteritinib treatment continued until participants met one of the treatment discontinuation criteria. | Participants received chemotherapy in 28-day cycles. Participants on Low-Dose Cytarabine (LoDAC) received 20 mg of cytarabine twice daily by subcutaneous (SC) or intravenous (IV) injection for 10 days. Participants on azacitidine received 75 mg/m^2 daily by SC or IV injection for 7 days. Participants on LoDAC or azacitidine treatment continued until they met discontinuation criteria. Participants on MEC chemotherapy received mitoxantrone 8 mg/m^2 daily by IV for 5 days, etoposide 100 mg/m^2 daily by IV for 5 days and cytarabine 1000 mg/m^2 daily by IV for 5 days (days 1-5). Participants on FLAG-IDA chemotherapy received G-CSF 300 μg/m^2 daily by SC/IV for 5 days (days 1-5), fludarabine 30 mg/m^2 daily by IV for 5 days (days 2-6), cytarabine 2000 mg/m^2 daily by IV for 5 days (days 2-6) and idarubicin 10 mg/m^2 daily by IV for 3 days (days 2-4). Participants receiving MEC or FLAG-IDA received 1 cycle of therapy and were assessed for response on or after day 15. |
Period Title: Overall Study | ||
Started | 247 | 124 |
Treated | 246 | 109 |
Completed [1] | 38 | 0 |
Not Completed | 209 | 124 |
Reason Not Completed | ||
Progressive disease | 70 | 16 |
Lack of Efficacy | 21 | 31 |
Death | 36 | 10 |
Disease relapse | 33 | 2 |
Adverse Event | 28 | 5 |
Withdrawal by Subject | 5 | 24 |
Physician Decision | 11 | 11 |
Completed 1 or 2 chemo cycles with CRs | 0 | 19 |
Miscellaneous | 4 | 5 |
Protocol deviation | 1 | 1 |
[1]
Participants still on treatment. Last assessment of remission status at the end of treatment visit.
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Baseline Characteristics
Arm/Group Title | Gilteritinib | Salvage Chemotherapy | Total | |
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Participants received 120 mg dose (3 tablets of 40 mg) orally once a day in continuous 28-day cycles, at least 2 hours after or 1 hour before food. Gilteritinib treatment continued until participants met one of the treatment discontinuation criteria. | Participants received chemotherapy in 28-day cycles. Participants on Low-Dose Cytarabine (LoDAC) received 20 mg of cytarabine twice daily by subcutaneous (SC) or intravenous (IV) injection for 10 days. Participants on azacitidine received 75 mg/m^2 daily by SC or IV injection for 7 days. Participants on LoDAC or azacitidine treatment continued until they met discontinuation criteria. Participants on MEC chemotherapy received mitoxantrone 8 mg/m^2 daily by IV for 5 days, etoposide 100 mg/m^2 daily by IV for 5 days and cytarabine 1000 mg/m^2 daily by IV for 5 days (days 1-5). Participants on FLAG-IDA chemotherapy received G-CSF 300 μg/m^2 daily by SC/IV for 5 days (days 1-5), fludarabine 30 mg/m^2 daily by IV for 5 days (days 2-6), cytarabine 2000 mg/m^2 daily by IV for 5 days (days 2-6) and idarubicin 10 mg/m^2 daily by IV for 3 days (days 2-4). Participants receiving MEC or FLAG-IDA received 1 cycle of therapy and were assessed for response on or after day 15. | Total of all reporting groups | |
Overall Number of Baseline Participants | 247 | 124 | 371 | |
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The analysis population was the Intention to Treatment (ITT), which consisted of all randomized participants.
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Age, Continuous
Mean (Standard Deviation) Unit of measure: Years |
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Number Analyzed | 247 participants | 124 participants | 371 participants | |
59 (14.6) | 57.6 (14.8) | 58.5 (14.7) | ||
Sex: Female, Male
Measure Type: Count of Participants Unit of measure: Participants |
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Number Analyzed | 247 participants | 124 participants | 371 participants | |
Female |
131 53.0%
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70 56.5%
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201 54.2%
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Male |
116 47.0%
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54 43.5%
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170 45.8%
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Race/Ethnicity, Customized
Measure Type: Count of Participants Unit of measure: Participants |
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Number Analyzed | 247 participants | 124 participants | 371 participants | |
WHITE |
145 58.7%
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75 60.5%
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220 59.3%
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ASIAN |
69 27.9%
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33 26.6%
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102 27.5%
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BLACK OR AFRICAN AMERICAN |
14 5.7%
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7 5.6%
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21 5.7%
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NATIVE HAWAIIAN OR OTHER PACIFIC ISLANDER |
1 0.4%
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0 0.0%
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1 0.3%
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AMERICAN INDIAN OR ALASKA NATIVE |
0 0.0%
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0 0.0%
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0 0.0%
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UNKNOWN |
4 1.6%
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4 3.2%
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8 2.2%
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OTHER |
5 2.0%
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1 0.8%
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6 1.6%
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MISSING |
9 3.6%
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4 3.2%
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13 3.5%
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Ethnicity
Measure Type: Count of Participants Unit of measure: Participants |
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Number Analyzed | 247 participants | 124 participants | 371 participants | |
NOT HISPANIC OR LATINO |
221 89.5%
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116 93.5%
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337 90.8%
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HISPANIC OR LATINO |
12 4.9%
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2 1.6%
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14 3.8%
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UNKNOWN |
3 1.2%
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2 1.6%
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5 1.3%
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MISSING |
11 4.5%
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4 3.2%
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15 4.0%
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Cytogenic Risk Status
[1] Measure Type: Count of Participants Unit of measure: Participants |
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Number Analyzed | 247 participants | 124 participants | 371 participants | |
INTERMEDIATE |
182 73.7%
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89 71.8%
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271 73.0%
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UNFAVORABLE |
26 10.5%
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11 8.9%
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37 10.0%
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FAVORABLE |
4 1.6%
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1 0.8%
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5 1.3%
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OTHER |
35 14.2%
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23 18.5%
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58 15.6%
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[1]
Measure Description: The category of "Other" includes those with cytogenetic risk status that cannot be categorized as favorable, intermediate or unfavorable.
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Baseline Eastern Cooperative Oncology Group (ECOG)
[1] Measure Type: Count of Participants Unit of measure: Participants |
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Number Analyzed | 247 participants | 124 participants | 371 participants | |
0-1 |
206 83.4%
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105 84.7%
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311 83.8%
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>=2 |
41 16.6%
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19 15.3%
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60 16.2%
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[1]
Measure Description: ECOG performance status is a scale used to assess impact on daily activities. It is based on the investigator assessment. Scores range from 0 to 5, with 0-signifying fully active participant; 1-restricted in physically strenuous activity; 2-ambulatory and capable of all self-care, unable to work; 3-capable of only limited self-care, confined to bed more than 50% of waking hours; 4-completely disabled and 5-dead. Negative numerical score indicates an improvement and positive numerical score indicates a decline in participant's daily activities, indicating disease progression.
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FLT3 Mutation Status by Central Testing by FLT3 CDx
Measure Type: Count of Participants Unit of measure: Participants |
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Number Analyzed | 247 participants | 124 participants | 371 participants | |
FLT3-ITD Alone |
215 87.0%
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113 91.1%
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328 88.4%
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FLT3-TKD Alone |
21 8.5%
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10 8.1%
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31 8.4%
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FLT3-ITD and FLT3-TKD |
7 2.8%
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0 0.0%
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7 1.9%
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Others (Unknown/Missing/Negative) |
4 1.6%
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1 0.8%
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5 1.3%
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Prior Use of FLT3 Inhibitor
[1] Measure Type: Count of Participants Unit of measure: Participants |
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Number Analyzed | 247 participants | 124 participants | 371 participants | |
No |
215 87.0%
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110 88.7%
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325 87.6%
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Yes |
32 13.0%
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14 11.3%
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46 12.4%
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[1]
Measure Description: Prior use of FLT3 inhibitor is defined as 'Yes' if participants received prior AML therapy of midostaurin, sorafenib or quizartinib; otherwise, prior use of FLT3 inhibitor is assigned as No.
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Region
Measure Type: Count of Participants Unit of measure: Participants |
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Number Analyzed | 247 participants | 124 participants | 371 participants | |
NORTH AMERICA |
114 46.2%
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52 41.9%
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166 44.7%
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EUROPE |
68 27.5%
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43 34.7%
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111 29.9%
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ASIA |
65 26.3%
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29 23.4%
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94 25.3%
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Baseline Body Surface Area (BSA)
[1] Mean (Standard Deviation) Unit of measure: M^2 |
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Number Analyzed | 199 participants | 122 participants | 321 participants | |
1.815 (0.281) | 1.777 (0.257) | 1.8 (0.272) | ||
[1]
Measure Analysis Population Description: The analysis population was the ITT, with available data.
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Baseline Height
[1] Mean (Standard Deviation) Unit of measure: Centimeter (cm) |
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Number Analyzed | 234 participants | 123 participants | 357 participants | |
167.25 (10.31) | 166.39 (10.63) | 166.95 (10.41) | ||
[1]
Measure Analysis Population Description: The analysis population was the ITT, with available data.
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Baseline Weight
[1] Mean (Standard Deviation) Unit of measure: Kilogram (kg) |
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Number Analyzed | 243 participants | 124 participants | 367 participants | |
72.79 (20.47) | 69.91 (19.73) | 71.82 (20.25) | ||
[1]
Measure Analysis Population Description: The analysis population was the ITT, with available data.
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Response to First Line Therapy
[1] Measure Type: Count of Participants Unit of measure: Participants |
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Primary refractory without HSCT | Number Analyzed | 247 participants | 124 participants | 371 participants |
98 39.7%
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48 38.7%
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146 39.4%
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Relapse within 6 months after CRc and no HSCT | Number Analyzed | 247 participants | 124 participants | 371 participants |
67 27.1%
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34 27.4%
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101 27.2%
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Relapse after 6 months after CRc and no HSCT | Number Analyzed | 247 participants | 124 participants | 371 participants |
34 13.8%
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17 13.7%
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51 13.7%
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Relapse within 6 months after allogeneic HSCT | Number Analyzed | 247 participants | 124 participants | 371 participants |
31 12.6%
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17 13.7%
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48 12.9%
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Relapse after 6 months after allogeneic HSCT | Number Analyzed | 247 participants | 124 participants | 371 participants |
17 6.9%
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8 6.5%
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25 6.7%
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[1]
Measure Description: Baseline stratification factors.
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Preselected Salvage Chemotherapy
[1] Measure Type: Count of Participants Unit of measure: Participants |
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High intensity chemotherapy | Number Analyzed | 247 participants | 124 participants | 371 participants |
149 60.3%
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75 60.5%
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224 60.4%
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Low intensity chemotherapy | Number Analyzed | 247 participants | 124 participants | 371 participants |
98 39.7%
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49 39.5%
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147 39.6%
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[1]
Measure Description: Baseline stratification factors.
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Response to First Line Therapy-Preselected Salvage Chemotherapy
[1] Measure Type: Count of Participants Unit of measure: Participants |
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Primary refractory w/o HSCT, high intensity (IT) | Number Analyzed | 247 participants | 124 participants | 371 participants |
57 23.1%
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28 22.6%
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85 22.9%
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Primary refractory w/o HSCT, low IT | Number Analyzed | 247 participants | 124 participants | 371 participants |
41 16.6%
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20 16.1%
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61 16.4%
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Relapse w/I 6 mths after CRc and no HSCT, high IT | Number Analyzed | 247 participants | 124 participants | 371 participants |
40 16.2%
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21 16.9%
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61 16.4%
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Relapse w/I 6 mths after CRc and no HSCT low IT | Number Analyzed | 247 participants | 124 participants | 371 participants |
27 10.9%
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13 10.5%
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40 10.8%
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Relapse after 6 mths after CRc and no HSCT high IT | Number Analyzed | 247 participants | 124 participants | 371 participants |
23 9.3%
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11 8.9%
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34 9.2%
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Relapse w/I 6 mths after allogeneic HSCT low IT | Number Analyzed | 247 participants | 124 participants | 371 participants |
16 6.5%
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9 7.3%
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25 6.7%
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Relapse w/I 6 mths after allogeneic HSCT high IT | Number Analyzed | 247 participants | 124 participants | 371 participants |
15 6.1%
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8 6.5%
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23 6.2%
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Relapse after 6 mths after allogeneic HSCT high IT | Number Analyzed | 247 participants | 124 participants | 371 participants |
14 5.7%
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7 5.6%
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21 5.7%
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Relapse after 6 mths after CRc and no HSCT low IT | Number Analyzed | 247 participants | 124 participants | 371 participants |
11 4.5%
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6 4.8%
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17 4.6%
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Relapse after 6 mths after allogeneic HSCT low IT | Number Analyzed | 247 participants | 124 participants | 371 participants |
3 1.2%
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1 0.8%
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4 1.1%
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[1]
Measure Description: Baseline stratification factors. HSCT is hematopoietic stem cell transplant. CRc is composite complete remission.
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Outcome Measures
Adverse Events
Limitations and Caveats
[Not Specified]
More Information
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts
the PI's rights to discuss or publish trial results after the trial is completed.
Institute and/or Principal Investigator may publish trial data generated at their specific study site after Sponsor publication of the multi-center data. Sponsor must receive a site's manuscript prior to publication for review and comment as specified in the Investigator Agreement.
Results Point of Contact
Name/Title: | Clinical Trial Disclosure |
Organization: | Astellas Pharma Global Development, Inc. |
Phone: | 800-888-7704 |
EMail: | astellas.resultsdisclosure@astellas.com |
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: | Astellas Pharma Inc ( Astellas Pharma Global Development, Inc. ) |
ClinicalTrials.gov Identifier: | NCT02421939 |
Other Study ID Numbers: |
2215-CL-0301 2015-000140-42 ( EudraCT Number ) |
First Submitted: | April 16, 2015 |
First Posted: | April 21, 2015 |
Results First Submitted: | September 12, 2019 |
Results First Posted: | October 17, 2019 |
Last Update Posted: | August 11, 2022 |