Acute Myelogenous Leukemia
Conditions
Keywords
acute myelogenous leukemia, acute myeloid leukemia, relapsed AML, refractory AML, clofarabine, cytarabine, CLO341, clolar
Brief summary
Clofarabine (injection) is approved by the Food and Drug Administration (FDA) for the treatment of pediatric patients 1 to 21 years old with relapsed acute or refractory lymphoblastic leukemia (ALL) who have had at least 2 prior treatment regimens. There is no recommended standard treatment for relapsed or refractory acute myelogenous leukemia in older patients. Cytarabine is the most commonly used drug to treat these patients. This study will determine if there is benefit by combining clofarabine with cytarabine. Patients will be randomized to receive up to 3 cycles of treatment with either placebo in combination with cytarabine or clofarabine in combination with cytarabine. Randomization was stratified by remission status following the first induction regimen (no remission \[i.e., CR1 = refractory\] or remission \<6 months vs CR1 = remission ≥6 months). CR1 is defined as remission after first pre-study induction regimen. The safety and tolerability of clofarabine in combination with cytarabine and cytarabine alone will be monitored throughout the study.
Detailed description
After screening and eligibility assessment, patients were randomized (in a 1:1 ratio) to receive either clofarabine or matching placebo, in addition to cytarabine. Randomization was stratified by remission status following the first induction regimen (CR1): no remission \[i.e., CR1 = refractory\] or remission \<6 months vs remission ≥6 months. During randomization by interactive voice response system (IVRS), there were 10 participants misclassified to the CR1 \<6 months stratum and 12 participants misclassified to CR1 ≥6 months stratum. The error did not affect the participants' treatment, only the stratification. Due to the misclassification, outcomes that used strata in their analysis were analyzed twice: once with the 'randomized stratification' which includes the misclassification and once with the 'calculated stratification' in which participants appear in the 'correct' strata. Two clinical study reports were written for this study. 1. Clinical study report dated 7 April 2011 includes the entire treatment period of all participants plus much of the follow-up. At that time, 33 participants in the Clofarabine+cytarabine group and 29 participants in the placebo+cytarabine group were still being follow-up post treatment. Results were reported on clinicaltrials.gov in August 2011. Outcomes that used strata reported the 'calculated strata' on clinicaltrials.gov. 2. Clinical study report dated 9 July 2012 includes all patient treatment experience plus all long-term follow-up (a minimum of 2 years from the end of treatment or until the patient died). The study was completed at that time. Outcomes that used strata reported the 'randomized strata' on clinicaltrials.gov. AE records on clinicaltrials.gov reflect the final database. Outcomes that changed between the two clinical study reports due to the additional long-term follow-up data are reported twice on clinicaltrials.gov (once from each clinical study report) and the appropriate report date is included in the outcome description. Outcomes from the 9 July 2012 report represent more complete data.
Interventions
clofarabine (IV formulation) infusion 40mg/m\^2 / day up to 3 cycles
DRUGplacebo
placebo (sodium Chloride) 1-hour IV infusion
DRUGcytarabine
cytarabine IV infusion 1g/m\^2/day for up to 3 cycles
Sponsors
Genzyme, a Sanofi Company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
55 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Have a diagnosis of Acute Myelogenous Leukemia (AML) according to World Health Organization (WHO) classification * Relapsed after receiving up to 2 prior induction regimens (i.e. first or second relapse)or are refractory to not more than one prior combination chemotherapy induction regimen * Be ≥ 55 years of age * Have an Eastern Cooperative Oncology Group (ECOG) score of 0-2 * Be able to comply with study procedures and follow-up examinations * Be nonfertile or agree to use birth control during the study through the end of treatment visit and for at least 90 days after the last dose of study drug * Have adequate liver and renal function as indicated by certain laboratory values
Exclusion criteria
* Received previous treatment with clofarabine * Received bolus, intermediate or high-dose cytarabine as induction therapy unless certain remission criteria are met * Have received a hematopoietic stem cell transplant (HSCT) within the previous 3 months * Have moderate or severe graft versus host disease (GVHD), whether acute or chronic * Are receiving any other chemotherapy or investigational therapy. Patients must have been off prior AML therapy for at least 2-6 weeks prior to entering study. * Have a psychiatric disorder that would interfere with consent, study participation, or follow-up * Have an active, uncontrolled infection * Have any other severe concurrent disease, or have a history of serious organ dysfunction or disease involving the heart, kidney, liver, or other organ system * Have been diagnosed with another malignancy, unless disease-free for at least 5 years; patients with treated nonmelanoma skin cancer, in situ carcinoma, or cervical intraepithelial neoplasia, regardless of the disease-free duration, are eligible for this study if definitive treatment for the condition has been completed; patients with organ-confined prostate cancer with no evidence of recurrent or progressive disease are eligible if hormonal therapy has been initiated or the malignancy has been surgically removed. * Have clinical evidence suggestive of central nervous system (CNS) involvement with leukemia unless lumbar puncture confirms absence of leukemic blasts in the cerebrospinal fluid(CSF) * Known HIV positivity * Are pregnant or lactating
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival - Overall and by Calculated Strata (CSR 7-April-11) | Day 1 (randomization) up to approximately 4 years | Overall survival (OS) for the Full Analysis Set (FAS) and for the 2 calculated strata. OS was defined as the number of months from date of randomization until date of death due to any cause. |
| Overall Survival - Overall and by Randomized Strata (CSR 9-July-12) | Day 1 (randomization) up to approximately 4 years | Overall survival (OS) for the Full Analysis Set (FAS) and for the 2 randomized strata. OS was defined as the number of months from date of randomization until date of death due to any cause. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Duration of Remission (DOR) Per IRRP Assessment-Overall and by Randomized Strata (CSR 9-July-12) | Day 12 to approximately 4 years | DOR was defined as the time from first CR or CRi to the date of first objective documentation of disease recurrence, initiation of alternative antileukemic therapy \[including hematopoietic stem cell transplant\] while in remission, or death due to any cause, whichever occurred first. CR is defined on morphologic criteria at a single response assessment: * a bone marrow aspirate or biopsy of \<5% blasts, with evidence of normal hematopoiesis; * absence of Auer rods in the blasts that are present; * absence of extramedullary disease; * absence of a unique phenotype determined at the pretreatment specimen, as assessed by immunophenotyping; * only rare evidence of circulating blasts. If present, evidence of a regenerating bone marrow; * recovery of peripheral counts (platelets ≥100\*10\^9/L and absolute neutrophil count (ANC) ≥1.0\*10\^9/L). CRi met all criteria for CR except for either residual neutropenia (ANC \<1.0\*10\^9/L) or thrombocytopenia (platelet count \<100\*10\^9/L). |
| Disease-free Survival by IRRP Assessment - Overall and by Calculated Strata (CSR 7-April-11) | Day 12 to approximately 4 years | Disease-free survival was defined as the time from first complete remission (CR) or complete remission with incomplete peripheral blood count recovery (CRi) until the date of first objective documentation of disease recurrence or death due to any cause, whichever occurred first. See Outcome #3 for definition of CR and CRi. Disease recurrence - reappearance of leukemic blasts in the peripheral blood, confirmed by ≥5% blasts in the bone marrow, and reappearance or development of pathologically proven extramedullary disease. |
| Disease-free Survival by IRRP Assessment - Overall and by Randomized Strata (CSR 9-July-12) | Day 12 to approximately 4 years | Disease-free survival was defined as the time from first complete remission (CR) or complete remission with incomplete peripheral blood count recovery (CRi) until the date of first objective documentation of disease recurrence or death due to any cause, whichever occurred first. See Outcome #3 for definition of CR and CRi. Disease recurrence - reappearance of leukemic blasts in the peripheral blood, confirmed by ≥5% blasts in the bone marrow, and reappearance or development of pathologically proven extramedullary disease. |
| Event-free Survival by IRRP Assessment - Overall and by Calculated Strata (CSR 7-April-11) | Day 1 (randomization) up to approximately 4 years | Event-free survival (EFS) was defined as the time from randomization to the date of treatment failure, first disease recurrence (for participants who achieved remission), or death due to any cause, whichever occurred first. Treatment Failure - ≥5% leukemic blasts by bone marrow exam, with no evidence of hematologic response (ie, \<30% decrease in % leukemic blasts). Disease recurrence - reappearance of leukemic blasts in the peripheral blood, confirmed by ≥5% blasts in the bone marrow, and reappearance or development of pathologically proven extramedullary disease. |
| Best Response Per Independent Response Review Panel (IRRP) Assessment - Overall and by Calculated Strata (CSR 7-April-11) | Day 12 up to approximately 6 months | Percentage of participants whose best response was assessed by the IRRP as complete remission (CR) or complete remission with incomplete peripheral blood count recovery (CRi) using the revised International Working Group for Response Criteria (Cheson 2003). CR is defined on morphologic criteria at a single response assessment: * a bone marrow aspirate or biopsy of \<5% blasts, with evidence of normal hematopoiesis; * absence of Auer rods in the blasts that are present; * absence of extramedullary disease; * absence of a unique phenotype determined at the pretreatment specimen, as assessed by immunophenotyping; * only rare evidence of circulating blasts. If present, evidence of a regenerating bone marrow; * recovery of peripheral counts (platelets ≥100\*10\^9/L and absolute neutrophil count (ANC) ≥1.0\*10\^9/L). CRi met all criteria for CR except for either residual neutropenia (ANC \<1.0\*10\^9/L) or thrombocytopenia (platelet count \<100\*10\^9/L). |
| Four-Month Event-free Survival Per IRRP Assessment - Overall and by Calculated Strata (CSR 7-April-11) | Day 1 (randomization) to Day 122 | Four-month event-free survival (EFS) was defined as achieving an EFS of at least 122 days, where EFS is defined as the time from randomization to the date of treatment failure, first disease recurrence (for participants who achieved remission), or death due to any cause, whichever occurred first. Treatment Failure - ≥5% leukemic blasts by bone marrow exam, with no evidence of hematologic response (ie, \<30% decrease in % leukemic blasts). Disease recurrence - reappearance of leukemic blasts in the peripheral blood, confirmed by ≥5% blasts in the bone marrow, and reappearance or development of pathologically proven extramedullary disease. |
| Four-Month Event-free Survival Per IRRP Assessment - Overall and by Randomized Strata (CSR 9-July-12) | Day 1 (randomization) to Day 122 | Four-month event-free survival (EFS) was defined as achieving an EFS of at least 122 days, where EFS is defined as the time from randomization to the date of treatment failure, first disease recurrence (for participants who achieved remission), or death due to any cause, whichever occurred first. Treatment Failure - ≥5% leukemic blasts by bone marrow exam, with no evidence of hematologic response (ie, \<30% decrease in % leukemic blasts). Disease recurrence - reappearance of leukemic blasts in the peripheral blood, confirmed by ≥5% blasts in the bone marrow, and reappearance or development of pathologically proven extramedullary disease. |
| Participants With Adverse Events (CSR 7-April-11) | Day 1 up to a maximum of 4 years (includes up to a maximum of 3 cycles of therapy plus 45 days follow up. Related AEs are followed to resolution.) | Number of participants with treatment emergent adverse events (TEAEs) or death due to related AE. Related AEs for the combination arm can be related to either clofarabine or cytarabine. Grade 1 = Mild AE, Grade 2 = Moderate AE, Grade 3 = Severe AE, Grade 4 = Life Threatening AE, Grade 5 = Death |
| Event-free Survival by IRRP Assessment - Overall and by Randomized Strata (CSR 9-July-12) | Day 1 (randomization) up to approximately 4 years | Event-free survival (EFS) was defined as the time from randomization to the date of treatment failure, first disease recurrence (for participants who achieved remission), or death due to any cause, whichever occurred first. Treatment Failure - ≥5% leukemic blasts by bone marrow exam, with no evidence of hematologic response (ie, \<30% decrease in % leukemic blasts). Disease recurrence - reappearance of leukemic blasts in the peripheral blood, confirmed by ≥5% blasts in the bone marrow, and reappearance or development of pathologically proven extramedullary disease. |
| Duration of Remission (DOR) Per IRRP Assessment-Overall and by Calculated Strata (CSR 7-April-11) | Day 12 to approximately 4 years | DOR was defined as the time from first CR or CRi to the date of first objective documentation of disease recurrence, initiation of alternative antileukemic therapy \[including hematopoietic stem cell transplant\] while in remission, or death due to any cause, whichever occurred first. CR is defined on morphologic criteria at a single response assessment: * a bone marrow aspirate or biopsy of \<5% blasts, with evidence of normal hematopoiesis; * absence of Auer rods in the blasts that are present; * absence of extramedullary disease; * absence of a unique phenotype determined at the pretreatment specimen, as assessed by immunophenotyping; * only rare evidence of circulating blasts. If present, evidence of a regenerating bone marrow; * recovery of peripheral counts (platelets ≥100\*10\^9/L and absolute neutrophil count (ANC) ≥1.0\*10\^9/L). CRi met all criteria for CR except for either residual neutropenia (ANC \<1.0\*10\^9/L) or thrombocytopenia (platelet count \<100\*10\^9/L). |
Countries
Canada, France, Germany, Italy, United States
Participant flow
Pre-assignment details
352 patients screened and 326 randomized, 163 to each treatment group. One participant withdrew after being randomized to the Placebo and Cytarabine Group and was excluded from efficacy analysis.
Participants by arm
| Arm | Count |
|---|---|
| Clofarabine (IV Formulation) and Cytarabine Participants received clofarabine 40 mg/m\^2 administered as a 1-hour intravenous (IV) infusion, followed 3 hours later (from end of infusion) by cytarabine 1 g/m\^2 administered as a 2-hour IV infusion for 5 days (induction and re-induction) or 4 days (consolidation). Participants could receive up to 3 cycles of treatment: induction, re-induction (if the participant had not achieved remission following induction but hematological improvement was noted), and consolidation. | 162 |
| Placebo and Cytarabine Participants received placebo (sodium chloride) administered as a 1-hour IV infusion, followed 3 hours later (from end of infusion) by cytarabine 1 g/m\^2 administered as a 2-hour IV infusion for 5 days (induction and re-induction) or 4 days (consolidation). Participants could receive up to 3 cycles of treatment: induction, re-induction, and consolidation. | 158 |
| Total | 320 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 17 | 5 |
| Overall Study | AML Not Centrally Confirmed | 1 | 5 |
| Overall Study | Death | 14 | 7 |
| Overall Study | Disease Recurrence | 1 | 2 |
| Overall Study | Not Continue to Consolidation | 2 | 0 |
| Overall Study | Not Received Either Study Drug | 1 | 3 |
| Overall Study | Participant declined treatment | 14 | 3 |
| Overall Study | Physician Decision | 15 | 7 |
| Overall Study | Referred For Transplantation | 1 | 0 |
| Overall Study | Treatment Failure | 56 | 102 |
| Overall Study | Withdrawal by Subject | 0 | 1 |
Baseline characteristics
| Characteristic | Placebo and Cytarabine | Total | Clofarabine (IV Formulation) and Cytarabine |
|---|---|---|---|
| Age, Continuous | 67.1 years STANDARD_DEVIATION 5.82 | 67.0 years STANDARD_DEVIATION 6.09 | 67.0 years STANDARD_DEVIATION 6.36 |
| Body Surface Area (BSA) | 1.959 m^2 STANDARD_DEVIATION 0.2338 | 1.950 m^2 STANDARD_DEVIATION 0.2359 | 1.941 m^2 STANDARD_DEVIATION 0.2383 |
| Eastern Cooperative Oncology Group Performance Status ECOG 0 | 48 Participants | 105 Participants | 57 Participants |
| Eastern Cooperative Oncology Group Performance Status ECOG 1 | 92 Participants | 171 Participants | 79 Participants |
| Eastern Cooperative Oncology Group Performance Status ECOG 2 | 18 Participants | 44 Participants | 26 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 6 Participants | 15 Participants | 9 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 152 Participants | 305 Participants | 153 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Height (cm) | 170.5 centimeter STANDARD_DEVIATION 8.92 | 171.0 centimeter STANDARD_DEVIATION 9.62 | 171.5 centimeter STANDARD_DEVIATION 10.27 |
| Karyotype Favorable | 0 participants | 1 participants | 1 participants |
| Karyotype Intermediate | 84 participants | 149 participants | 65 participants |
| Karyotype Not Assessed | 3 participants | 11 participants | 8 participants |
| Karyotype Unfavorable | 70 participants | 156 participants | 86 participants |
| Karyotype unknown | 1 participants | 3 participants | 2 participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 5 Participants | 3 Participants |
| Race (NIH/OMB) Black or African American | 11 Participants | 18 Participants | 7 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 3 Participants | 5 Participants | 2 Participants |
| Race (NIH/OMB) White | 142 Participants | 292 Participants | 150 Participants |
| Sex: Female, Male Female | 57 Participants | 105 Participants | 48 Participants |
| Sex: Female, Male Male | 101 Participants | 215 Participants | 114 Participants |
| Weight(kg) | 83.03 kg STANDARD_DEVIATION 17.281 | 82.11 kg STANDARD_DEVIATION 17.574 | 81.21 kg STANDARD_DEVIATION 17.862 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 161 / 161 | 154 / 155 | 315 / 316 |
| serious Total, serious adverse events | 97 / 161 | 76 / 155 | 173 / 316 |
Outcome results
Primary
Overall Survival - Overall and by Calculated Strata (CSR 7-April-11)
Overall survival (OS) for the Full Analysis Set (FAS) and for the 2 calculated strata. OS was defined as the number of months from date of randomization until date of death due to any cause.
Time frame: Day 1 (randomization) up to approximately 4 years
Population: Full Analysis Set (FAS)-all randomized participants whose baseline AML diagnosis was centrally confirmed. Strata are calculated according to duration of the first remission based on case report forms (CRF) data and do not include the IVRS mistakes. One participant's strata (placebo group) could not be calculated so the participant was excluded.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Clofarabine (IV Formulation) and Cytarabine (FAS) | Overall Survival - Overall and by Calculated Strata (CSR 7-April-11) | 6.6 months |
| Placebo and Cytarabine (FAS) | Overall Survival - Overall and by Calculated Strata (CSR 7-April-11) | 6.4 months |
| Clofarabine and Cytarabine - In Stratum < 6 Months | Overall Survival - Overall and by Calculated Strata (CSR 7-April-11) | 5.1 months |
| Placebo and Cytarabine - In Stratum < 6 Months | Overall Survival - Overall and by Calculated Strata (CSR 7-April-11) | 5.5 months |
| Clofarabine and Cytarabine In Stratum >= 6 Months | Overall Survival - Overall and by Calculated Strata (CSR 7-April-11) | 8.7 months |
| Placebo and Cytarabine In Stratum >= 6 Months | Overall Survival - Overall and by Calculated Strata (CSR 7-April-11) | 7.2 months |
Comparison: Full Analysis Set (FAS) populationp-value: 0.995195% CI: [0.78, 1.28]Log Rank
Comparison: Participants stratified by calculated strata remission after first pre-study induction regimen (CR1) \< 6 monthsp-value: 0.467495% CI: [0.81, 1.57]Log Rank
Comparison: Participants stratified by calculated strata CR1\>= 6 monthsp-value: 0.396395% CI: [0.58, 1.24]Log Rank
Primary
Overall Survival - Overall and by Randomized Strata (CSR 9-July-12)
Overall survival (OS) for the Full Analysis Set (FAS) and for the 2 randomized strata. OS was defined as the number of months from date of randomization until date of death due to any cause.
Time frame: Day 1 (randomization) up to approximately 4 years
Population: Full Analysis Set (FAS) - composed of all randomized participants whose baseline AML diagnosis was centrally confirmed. Strata are as randomized by the IVRS, therefore strata include the IVRS mistakes.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Clofarabine (IV Formulation) and Cytarabine (FAS) | Overall Survival - Overall and by Randomized Strata (CSR 9-July-12) | 6.6 months |
| Placebo and Cytarabine (FAS) | Overall Survival - Overall and by Randomized Strata (CSR 9-July-12) | 6.3 months |
| Clofarabine and Cytarabine - In Stratum < 6 Months | Overall Survival - Overall and by Randomized Strata (CSR 9-July-12) | 4.8 months |
| Placebo and Cytarabine - In Stratum < 6 Months | Overall Survival - Overall and by Randomized Strata (CSR 9-July-12) | 6.3 months |
| Clofarabine and Cytarabine In Stratum >= 6 Months | Overall Survival - Overall and by Randomized Strata (CSR 9-July-12) | 9.7 months |
| Placebo and Cytarabine In Stratum >= 6 Months | Overall Survival - Overall and by Randomized Strata (CSR 9-July-12) | 6.6 months |
Comparison: Full Analysis Set (FAS) populationp-value: 0.820995% CI: [0.77, 1.23]Log Rank
p-value: 0.507195% CI: [0.81, 1.53]Log Rank
p-value: 0.290695% CI: [0.59, 1.17]Log Rank
Secondary
Best Response Per Independent Response Review Panel (IRRP) Assessment - Overall and by Calculated Strata (CSR 7-April-11)
Percentage of participants whose best response was assessed by the IRRP as complete remission (CR) or complete remission with incomplete peripheral blood count recovery (CRi) using the revised International Working Group for Response Criteria (Cheson 2003). CR is defined on morphologic criteria at a single response assessment: * a bone marrow aspirate or biopsy of \<5% blasts, with evidence of normal hematopoiesis; * absence of Auer rods in the blasts that are present; * absence of extramedullary disease; * absence of a unique phenotype determined at the pretreatment specimen, as assessed by immunophenotyping; * only rare evidence of circulating blasts. If present, evidence of a regenerating bone marrow; * recovery of peripheral counts (platelets ≥100\*10\^9/L and absolute neutrophil count (ANC) ≥1.0\*10\^9/L). CRi met all criteria for CR except for either residual neutropenia (ANC \<1.0\*10\^9/L) or thrombocytopenia (platelet count \<100\*10\^9/L).
Time frame: Day 12 up to approximately 6 months
Population: Full Analysis Set (FAS)-all randomized participants whose baseline AML diagnosis was centrally confirmed. Strata are calculated according to duration of the first remission based on case report forms (CRF) data and do not include the IVRS mistakes. One participant's strata (placebo group) could not be calculated so the participant was excluded.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Clofarabine (IV Formulation) and Cytarabine (FAS) | Best Response Per Independent Response Review Panel (IRRP) Assessment - Overall and by Calculated Strata (CSR 7-April-11) | Complete Remission (CR) | 35.2 percentage of participants |
| Clofarabine (IV Formulation) and Cytarabine (FAS) | Best Response Per Independent Response Review Panel (IRRP) Assessment - Overall and by Calculated Strata (CSR 7-April-11) | Overall Remission (CR + CRi) | 46.9 percentage of participants |
| Clofarabine (IV Formulation) and Cytarabine (FAS) | Best Response Per Independent Response Review Panel (IRRP) Assessment - Overall and by Calculated Strata (CSR 7-April-11) | CR with incomplete blood count recovery (CRi) | 11.7 percentage of participants |
| Placebo and Cytarabine (FAS) | Best Response Per Independent Response Review Panel (IRRP) Assessment - Overall and by Calculated Strata (CSR 7-April-11) | Complete Remission (CR) | 17.8 percentage of participants |
| Placebo and Cytarabine (FAS) | Best Response Per Independent Response Review Panel (IRRP) Assessment - Overall and by Calculated Strata (CSR 7-April-11) | Overall Remission (CR + CRi) | 22.9 percentage of participants |
| Placebo and Cytarabine (FAS) | Best Response Per Independent Response Review Panel (IRRP) Assessment - Overall and by Calculated Strata (CSR 7-April-11) | CR with incomplete blood count recovery (CRi) | 5.1 percentage of participants |
| Clofarabine and Cytarabine - In Stratum < 6 Months | Best Response Per Independent Response Review Panel (IRRP) Assessment - Overall and by Calculated Strata (CSR 7-April-11) | Complete Remission (CR) | 33.0 percentage of participants |
| Clofarabine and Cytarabine - In Stratum < 6 Months | Best Response Per Independent Response Review Panel (IRRP) Assessment - Overall and by Calculated Strata (CSR 7-April-11) | Overall Remission (CR + CRi) | 45.5 percentage of participants |
| Clofarabine and Cytarabine - In Stratum < 6 Months | Best Response Per Independent Response Review Panel (IRRP) Assessment - Overall and by Calculated Strata (CSR 7-April-11) | CR with incomplete blood count recovery (CRi) | 12.5 percentage of participants |
| Placebo and Cytarabine - In Stratum < 6 Months | Best Response Per Independent Response Review Panel (IRRP) Assessment - Overall and by Calculated Strata (CSR 7-April-11) | Complete Remission (CR) | 18.1 percentage of participants |
| Placebo and Cytarabine - In Stratum < 6 Months | Best Response Per Independent Response Review Panel (IRRP) Assessment - Overall and by Calculated Strata (CSR 7-April-11) | Overall Remission (CR + CRi) | 22.9 percentage of participants |
| Placebo and Cytarabine - In Stratum < 6 Months | Best Response Per Independent Response Review Panel (IRRP) Assessment - Overall and by Calculated Strata (CSR 7-April-11) | CR with incomplete blood count recovery (CRi) | 4.8 percentage of participants |
| Clofarabine and Cytarabine In Stratum >= 6 Months | Best Response Per Independent Response Review Panel (IRRP) Assessment - Overall and by Calculated Strata (CSR 7-April-11) | Complete Remission (CR) | 37.8 percentage of participants |
| Clofarabine and Cytarabine In Stratum >= 6 Months | Best Response Per Independent Response Review Panel (IRRP) Assessment - Overall and by Calculated Strata (CSR 7-April-11) | Overall Remission (CR + CRi) | 48.6 percentage of participants |
| Clofarabine and Cytarabine In Stratum >= 6 Months | Best Response Per Independent Response Review Panel (IRRP) Assessment - Overall and by Calculated Strata (CSR 7-April-11) | CR with incomplete blood count recovery (CRi) | 10.8 percentage of participants |
| Placebo and Cytarabine In Stratum >= 6 Months | Best Response Per Independent Response Review Panel (IRRP) Assessment - Overall and by Calculated Strata (CSR 7-April-11) | Overall Remission (CR + CRi) | 23.0 percentage of participants |
| Placebo and Cytarabine In Stratum >= 6 Months | Best Response Per Independent Response Review Panel (IRRP) Assessment - Overall and by Calculated Strata (CSR 7-April-11) | CR with incomplete blood count recovery (CRi) | 5.4 percentage of participants |
| Placebo and Cytarabine In Stratum >= 6 Months | Best Response Per Independent Response Review Panel (IRRP) Assessment - Overall and by Calculated Strata (CSR 7-April-11) | Complete Remission (CR) | 17.6 percentage of participants |
Comparison: Full Analysis Set (FAS) population - overall remission (OR)p-value: <0.0001Cochran-Mantel-Haenszel
Comparison: Full Analysis Set (FAS) population - Complete Remission (CR)p-value: 0.0005Cochran-Mantel-Haenszel
Comparison: Participants stratified by calculated strata - CR1 \<6 months \[Overall Remission (CR+CRi)\]p-value: 0.0022Fisher Exact
Comparison: Participants stratified by calculated strata - CR1 \>=6 months \[Overall Remission (CR+CRi)\]p-value: 0.0019Fisher Exact
Comparison: Participants stratified by calculated strata - CR1 \<6 months \[Complete Remission (CR)\]p-value: 0.0353Fisher Exact
Comparison: Participants stratified by calculated strata - CR1 \>=6 months \[Complete Remission (CR)\]p-value: 0.0096Fisher Exact
Secondary
Disease-free Survival by IRRP Assessment - Overall and by Calculated Strata (CSR 7-April-11)
Disease-free survival was defined as the time from first complete remission (CR) or complete remission with incomplete peripheral blood count recovery (CRi) until the date of first objective documentation of disease recurrence or death due to any cause, whichever occurred first. See Outcome #3 for definition of CR and CRi. Disease recurrence - reappearance of leukemic blasts in the peripheral blood, confirmed by ≥5% blasts in the bone marrow, and reappearance or development of pathologically proven extramedullary disease.
Time frame: Day 12 to approximately 4 years
Population: Participants in the FAS who achieved OR (CR + CRi). Strata are calculated according to duration of the first remission based on case report forms (CRF) data and do not include the IVRS mistakes.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Clofarabine (IV Formulation) and Cytarabine (FAS) | Disease-free Survival by IRRP Assessment - Overall and by Calculated Strata (CSR 7-April-11) | 8.1 months |
| Placebo and Cytarabine (FAS) | Disease-free Survival by IRRP Assessment - Overall and by Calculated Strata (CSR 7-April-11) | 7.0 months |
| Clofarabine and Cytarabine - In Stratum < 6 Months | Disease-free Survival by IRRP Assessment - Overall and by Calculated Strata (CSR 7-April-11) | 5.7 months |
| Placebo and Cytarabine - In Stratum < 6 Months | Disease-free Survival by IRRP Assessment - Overall and by Calculated Strata (CSR 7-April-11) | 6.7 months |
| Clofarabine and Cytarabine In Stratum >= 6 Months | Disease-free Survival by IRRP Assessment - Overall and by Calculated Strata (CSR 7-April-11) | 10.3 months |
| Placebo and Cytarabine In Stratum >= 6 Months | Disease-free Survival by IRRP Assessment - Overall and by Calculated Strata (CSR 7-April-11) | 9.1 months |
Secondary
Disease-free Survival by IRRP Assessment - Overall and by Randomized Strata (CSR 9-July-12)
Disease-free survival was defined as the time from first complete remission (CR) or complete remission with incomplete peripheral blood count recovery (CRi) until the date of first objective documentation of disease recurrence or death due to any cause, whichever occurred first. See Outcome #3 for definition of CR and CRi. Disease recurrence - reappearance of leukemic blasts in the peripheral blood, confirmed by ≥5% blasts in the bone marrow, and reappearance or development of pathologically proven extramedullary disease.
Time frame: Day 12 to approximately 4 years
Population: Participants in the FAS who achieved OR (CR + CRi). Strata are as randomized by the IVRS, therefore strata include the IVRS mistakes.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Clofarabine (IV Formulation) and Cytarabine (FAS) | Disease-free Survival by IRRP Assessment - Overall and by Randomized Strata (CSR 9-July-12) | 9.5 months |
| Placebo and Cytarabine (FAS) | Disease-free Survival by IRRP Assessment - Overall and by Randomized Strata (CSR 9-July-12) | 7.0 months |
| Clofarabine and Cytarabine - In Stratum < 6 Months | Disease-free Survival by IRRP Assessment - Overall and by Randomized Strata (CSR 9-July-12) | 6.7 months |
| Placebo and Cytarabine - In Stratum < 6 Months | Disease-free Survival by IRRP Assessment - Overall and by Randomized Strata (CSR 9-July-12) | 6.7 months |
| Clofarabine and Cytarabine In Stratum >= 6 Months | Disease-free Survival by IRRP Assessment - Overall and by Randomized Strata (CSR 9-July-12) | 15.4 months |
| Placebo and Cytarabine In Stratum >= 6 Months | Disease-free Survival by IRRP Assessment - Overall and by Randomized Strata (CSR 9-July-12) | 9.2 months |
Secondary
Duration of Remission (DOR) Per IRRP Assessment-Overall and by Calculated Strata (CSR 7-April-11)
DOR was defined as the time from first CR or CRi to the date of first objective documentation of disease recurrence, initiation of alternative antileukemic therapy \[including hematopoietic stem cell transplant\] while in remission, or death due to any cause, whichever occurred first. CR is defined on morphologic criteria at a single response assessment: * a bone marrow aspirate or biopsy of \<5% blasts, with evidence of normal hematopoiesis; * absence of Auer rods in the blasts that are present; * absence of extramedullary disease; * absence of a unique phenotype determined at the pretreatment specimen, as assessed by immunophenotyping; * only rare evidence of circulating blasts. If present, evidence of a regenerating bone marrow; * recovery of peripheral counts (platelets ≥100\*10\^9/L and absolute neutrophil count (ANC) ≥1.0\*10\^9/L). CRi met all criteria for CR except for either residual neutropenia (ANC \<1.0\*10\^9/L) or thrombocytopenia (platelet count \<100\*10\^9/L).
Time frame: Day 12 to approximately 4 years
Population: Participants in the FAS who achieved OR (CR + CRi). Strata are calculated according to duration of the first remission based on case report forms (CRF) data and do not include the IVRS mistakes.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Clofarabine (IV Formulation) and Cytarabine (FAS) | Duration of Remission (DOR) Per IRRP Assessment-Overall and by Calculated Strata (CSR 7-April-11) | 7.6 months |
| Placebo and Cytarabine (FAS) | Duration of Remission (DOR) Per IRRP Assessment-Overall and by Calculated Strata (CSR 7-April-11) | 3.8 months |
| Clofarabine and Cytarabine - In Stratum < 6 Months | Duration of Remission (DOR) Per IRRP Assessment-Overall and by Calculated Strata (CSR 7-April-11) | 5.7 months |
| Placebo and Cytarabine - In Stratum < 6 Months | Duration of Remission (DOR) Per IRRP Assessment-Overall and by Calculated Strata (CSR 7-April-11) | 6.3 months |
| Clofarabine and Cytarabine In Stratum >= 6 Months | Duration of Remission (DOR) Per IRRP Assessment-Overall and by Calculated Strata (CSR 7-April-11) | 11.5 months |
| Placebo and Cytarabine In Stratum >= 6 Months | Duration of Remission (DOR) Per IRRP Assessment-Overall and by Calculated Strata (CSR 7-April-11) | 3.8 months |
Secondary
Duration of Remission (DOR) Per IRRP Assessment-Overall and by Randomized Strata (CSR 9-July-12)
DOR was defined as the time from first CR or CRi to the date of first objective documentation of disease recurrence, initiation of alternative antileukemic therapy \[including hematopoietic stem cell transplant\] while in remission, or death due to any cause, whichever occurred first. CR is defined on morphologic criteria at a single response assessment: * a bone marrow aspirate or biopsy of \<5% blasts, with evidence of normal hematopoiesis; * absence of Auer rods in the blasts that are present; * absence of extramedullary disease; * absence of a unique phenotype determined at the pretreatment specimen, as assessed by immunophenotyping; * only rare evidence of circulating blasts. If present, evidence of a regenerating bone marrow; * recovery of peripheral counts (platelets ≥100\*10\^9/L and absolute neutrophil count (ANC) ≥1.0\*10\^9/L). CRi met all criteria for CR except for either residual neutropenia (ANC \<1.0\*10\^9/L) or thrombocytopenia (platelet count \<100\*10\^9/L).
Time frame: Day 12 to approximately 4 years
Population: Participants in the FAS who achieved OR (CR + CRi). Strata are as randomized by the IVRS, therefore strata include the IVRS mistakes.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Clofarabine (IV Formulation) and Cytarabine (FAS) | Duration of Remission (DOR) Per IRRP Assessment-Overall and by Randomized Strata (CSR 9-July-12) | 7.7 months |
| Placebo and Cytarabine (FAS) | Duration of Remission (DOR) Per IRRP Assessment-Overall and by Randomized Strata (CSR 9-July-12) | 3.8 months |
| Clofarabine and Cytarabine - In Stratum < 6 Months | Duration of Remission (DOR) Per IRRP Assessment-Overall and by Randomized Strata (CSR 9-July-12) | 6.7 months |
| Placebo and Cytarabine - In Stratum < 6 Months | Duration of Remission (DOR) Per IRRP Assessment-Overall and by Randomized Strata (CSR 9-July-12) | 6.3 months |
| Clofarabine and Cytarabine In Stratum >= 6 Months | Duration of Remission (DOR) Per IRRP Assessment-Overall and by Randomized Strata (CSR 9-July-12) | 10.2 months |
| Placebo and Cytarabine In Stratum >= 6 Months | Duration of Remission (DOR) Per IRRP Assessment-Overall and by Randomized Strata (CSR 9-July-12) | 3.8 months |
Secondary
Event-free Survival by IRRP Assessment - Overall and by Calculated Strata (CSR 7-April-11)
Event-free survival (EFS) was defined as the time from randomization to the date of treatment failure, first disease recurrence (for participants who achieved remission), or death due to any cause, whichever occurred first. Treatment Failure - ≥5% leukemic blasts by bone marrow exam, with no evidence of hematologic response (ie, \<30% decrease in % leukemic blasts). Disease recurrence - reappearance of leukemic blasts in the peripheral blood, confirmed by ≥5% blasts in the bone marrow, and reappearance or development of pathologically proven extramedullary disease.
Time frame: Day 1 (randomization) up to approximately 4 years
Population: Full Analysis Set (FAS)-all randomized participants whose baseline AML diagnosis was centrally confirmed. Strata are calculated according to duration of the first remission based on case report forms (CRF) data and do not include the IVRS mistakes. One participant's strata (placebo group) could not be calculated so the participant was excluded.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Clofarabine (IV Formulation) and Cytarabine (FAS) | Event-free Survival by IRRP Assessment - Overall and by Calculated Strata (CSR 7-April-11) | 1.9 months |
| Placebo and Cytarabine (FAS) | Event-free Survival by IRRP Assessment - Overall and by Calculated Strata (CSR 7-April-11) | 1.0 months |
| Clofarabine and Cytarabine - In Stratum < 6 Months | Event-free Survival by IRRP Assessment - Overall and by Calculated Strata (CSR 7-April-11) | 1.4 months |
| Placebo and Cytarabine - In Stratum < 6 Months | Event-free Survival by IRRP Assessment - Overall and by Calculated Strata (CSR 7-April-11) | 1.0 months |
| Clofarabine and Cytarabine In Stratum >= 6 Months | Event-free Survival by IRRP Assessment - Overall and by Calculated Strata (CSR 7-April-11) | 2.0 months |
| Placebo and Cytarabine In Stratum >= 6 Months | Event-free Survival by IRRP Assessment - Overall and by Calculated Strata (CSR 7-April-11) | 1.0 months |
Comparison: Full Analysis Set (FAS) population.p-value: 0.000195% CI: [0.49, 0.8]Log Rank
Comparison: Participants stratified by randomization strata CR1 \<6 monthsp-value: 0.013195% CI: [0.49, 0.93]Log Rank
Comparison: Participants stratified by randomization strata CR1 \>=6 monthsp-value: 0.002295% CI: [0.4, 0.83]Log Rank
Secondary
Event-free Survival by IRRP Assessment - Overall and by Randomized Strata (CSR 9-July-12)
Event-free survival (EFS) was defined as the time from randomization to the date of treatment failure, first disease recurrence (for participants who achieved remission), or death due to any cause, whichever occurred first. Treatment Failure - ≥5% leukemic blasts by bone marrow exam, with no evidence of hematologic response (ie, \<30% decrease in % leukemic blasts). Disease recurrence - reappearance of leukemic blasts in the peripheral blood, confirmed by ≥5% blasts in the bone marrow, and reappearance or development of pathologically proven extramedullary disease.
Time frame: Day 1 (randomization) up to approximately 4 years
Population: Full Analysis Set - composed of all randomized participants whose baseline AML diagnosis was centrally confirmed. Strata are as randomized by the IVRS, therefore strata include the IVRS mistakes.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Clofarabine (IV Formulation) and Cytarabine (FAS) | Event-free Survival by IRRP Assessment - Overall and by Randomized Strata (CSR 9-July-12) | 1.9 months |
| Placebo and Cytarabine (FAS) | Event-free Survival by IRRP Assessment - Overall and by Randomized Strata (CSR 9-July-12) | 1.0 months |
| Clofarabine and Cytarabine - In Stratum < 6 Months | Event-free Survival by IRRP Assessment - Overall and by Randomized Strata (CSR 9-July-12) | 1.1 months |
| Placebo and Cytarabine - In Stratum < 6 Months | Event-free Survival by IRRP Assessment - Overall and by Randomized Strata (CSR 9-July-12) | 1.0 months |
| Clofarabine and Cytarabine In Stratum >= 6 Months | Event-free Survival by IRRP Assessment - Overall and by Randomized Strata (CSR 9-July-12) | 2.8 months |
| Placebo and Cytarabine In Stratum >= 6 Months | Event-free Survival by IRRP Assessment - Overall and by Randomized Strata (CSR 9-July-12) | 1.0 months |
Comparison: Full Analysis Set (FAS) population.p-value: <0.000195% CI: [0.49, 0.79]Log Rank
p-value: 0.048695% CI: [0.53, 1.01]Log Rank
p-value: 0.000295% CI: [0.37, 0.74]Log Rank
Secondary
Four-Month Event-free Survival Per IRRP Assessment - Overall and by Calculated Strata (CSR 7-April-11)
Four-month event-free survival (EFS) was defined as achieving an EFS of at least 122 days, where EFS is defined as the time from randomization to the date of treatment failure, first disease recurrence (for participants who achieved remission), or death due to any cause, whichever occurred first. Treatment Failure - ≥5% leukemic blasts by bone marrow exam, with no evidence of hematologic response (ie, \<30% decrease in % leukemic blasts). Disease recurrence - reappearance of leukemic blasts in the peripheral blood, confirmed by ≥5% blasts in the bone marrow, and reappearance or development of pathologically proven extramedullary disease.
Time frame: Day 1 (randomization) to Day 122
Population: Full Analysis Set (FAS)-all randomized participants whose baseline AML diagnosis was centrally confirmed. Strata are calculated according to duration of the first remission based on case report forms (CRF) data and do not include the IVRS mistakes. One participant's strata (placebo group) could not be calculated so the participant was excluded.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Clofarabine (IV Formulation) and Cytarabine (FAS) | Four-Month Event-free Survival Per IRRP Assessment - Overall and by Calculated Strata (CSR 7-April-11) | 37.7 percentage of participants |
| Placebo and Cytarabine (FAS) | Four-Month Event-free Survival Per IRRP Assessment - Overall and by Calculated Strata (CSR 7-April-11) | 16.6 percentage of participants |
| Clofarabine and Cytarabine - In Stratum < 6 Months | Four-Month Event-free Survival Per IRRP Assessment - Overall and by Calculated Strata (CSR 7-April-11) | 35.2 percentage of participants |
| Placebo and Cytarabine - In Stratum < 6 Months | Four-Month Event-free Survival Per IRRP Assessment - Overall and by Calculated Strata (CSR 7-April-11) | 16.9 percentage of participants |
| Clofarabine and Cytarabine In Stratum >= 6 Months | Four-Month Event-free Survival Per IRRP Assessment - Overall and by Calculated Strata (CSR 7-April-11) | 40.5 percentage of participants |
| Placebo and Cytarabine In Stratum >= 6 Months | Four-Month Event-free Survival Per IRRP Assessment - Overall and by Calculated Strata (CSR 7-April-11) | 16.2 percentage of participants |
Comparison: Full Analysis Set (FAS) populationp-value: <0.0001Cochran-Mantel-Haenszel
Comparison: Participants stratified by randomization strata CR1 \<6 months.p-value: 0.0088Fisher Exact
Comparison: Participants stratified by randomization strata CR1 \>=6 monthsp-value: 0.0017Fisher Exact
Secondary
Four-Month Event-free Survival Per IRRP Assessment - Overall and by Randomized Strata (CSR 9-July-12)
Four-month event-free survival (EFS) was defined as achieving an EFS of at least 122 days, where EFS is defined as the time from randomization to the date of treatment failure, first disease recurrence (for participants who achieved remission), or death due to any cause, whichever occurred first. Treatment Failure - ≥5% leukemic blasts by bone marrow exam, with no evidence of hematologic response (ie, \<30% decrease in % leukemic blasts). Disease recurrence - reappearance of leukemic blasts in the peripheral blood, confirmed by ≥5% blasts in the bone marrow, and reappearance or development of pathologically proven extramedullary disease.
Time frame: Day 1 (randomization) to Day 122
Population: Full Analysis Set - composed of all randomized participants whose baseline AML diagnosis was centrally confirmed. Strata are as randomized by the IVRS, that is the strata include the IVRS mistakes.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Clofarabine (IV Formulation) and Cytarabine (FAS) | Four-Month Event-free Survival Per IRRP Assessment - Overall and by Randomized Strata (CSR 9-July-12) | 38.9 percentage of participants |
| Placebo and Cytarabine (FAS) | Four-Month Event-free Survival Per IRRP Assessment - Overall and by Randomized Strata (CSR 9-July-12) | 17.1 percentage of participants |
| Clofarabine and Cytarabine - In Stratum < 6 Months | Four-Month Event-free Survival Per IRRP Assessment - Overall and by Randomized Strata (CSR 9-July-12) | 31.4 percentage of participants |
| Placebo and Cytarabine - In Stratum < 6 Months | Four-Month Event-free Survival Per IRRP Assessment - Overall and by Randomized Strata (CSR 9-July-12) | 17.9 percentage of participants |
| Clofarabine and Cytarabine In Stratum >= 6 Months | Four-Month Event-free Survival Per IRRP Assessment - Overall and by Randomized Strata (CSR 9-July-12) | 47.4 percentage of participants |
| Placebo and Cytarabine In Stratum >= 6 Months | Four-Month Event-free Survival Per IRRP Assessment - Overall and by Randomized Strata (CSR 9-July-12) | 16.2 percentage of participants |
p-value: <0.0001Cochran-Mantel-Haenszel
p-value: 0.0506Fisher Exact
p-value: <0.0001Fisher Exact
Secondary
Participants With Adverse Events (CSR 7-April-11)
Number of participants with treatment emergent adverse events (TEAEs) or death due to related AE. Related AEs for the combination arm can be related to either clofarabine or cytarabine. Grade 1 = Mild AE, Grade 2 = Moderate AE, Grade 3 = Severe AE, Grade 4 = Life Threatening AE, Grade 5 = Death
Time frame: Day 1 up to a maximum of 4 years (includes up to a maximum of 3 cycles of therapy plus 45 days follow up. Related AEs are followed to resolution.)
Population: Safety Set - Participants in the Full Analysis Set (FAS) who received at least 1 dose of study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Clofarabine (IV Formulation) and Cytarabine (FAS) | Participants With Adverse Events (CSR 7-April-11) | Any Treatment Emergent AE | 161 participants |
| Clofarabine (IV Formulation) and Cytarabine (FAS) | Participants With Adverse Events (CSR 7-April-11) | Any Related Treatment Emergent AE | 157 participants |
| Clofarabine (IV Formulation) and Cytarabine (FAS) | Participants With Adverse Events (CSR 7-April-11) | Any Treatment Emergent Grade >=3 AE | 157 participants |
| Clofarabine (IV Formulation) and Cytarabine (FAS) | Participants With Adverse Events (CSR 7-April-11) | Any Related Treatment Related Grade >=3 AE | 127 participants |
| Clofarabine (IV Formulation) and Cytarabine (FAS) | Participants With Adverse Events (CSR 7-April-11) | Discontinue of study medication due to AE | 17 participants |
| Clofarabine (IV Formulation) and Cytarabine (FAS) | Participants With Adverse Events (CSR 7-April-11) | Discontinue of study medication due to related AE | 14 participants |
| Placebo and Cytarabine (FAS) | Participants With Adverse Events (CSR 7-April-11) | Discontinue of study medication due to AE | 5 participants |
| Placebo and Cytarabine (FAS) | Participants With Adverse Events (CSR 7-April-11) | Any Treatment Emergent AE | 155 participants |
| Placebo and Cytarabine (FAS) | Participants With Adverse Events (CSR 7-April-11) | Any Related Treatment Related Grade >=3 AE | 83 participants |
| Placebo and Cytarabine (FAS) | Participants With Adverse Events (CSR 7-April-11) | Any Related Treatment Emergent AE | 133 participants |
| Placebo and Cytarabine (FAS) | Participants With Adverse Events (CSR 7-April-11) | Discontinue of study medication due to related AE | 3 participants |
| Placebo and Cytarabine (FAS) | Participants With Adverse Events (CSR 7-April-11) | Any Treatment Emergent Grade >=3 AE | 133 participants |