Leukemia, Myeloid, Acute
Conditions
Keywords
FLT3-ITD positive Acute Myeloid Leukemia (AML), AC220, Relapse, Refractory
Brief summary
This study will evaluate two doses of Quizartinib in patients with relapsed or refractory acute myeloid leukemia who are also FMS-like tyrosine kinase - internal tandem duplication ( FLT3-ITD) positive. Patient will be randomly assigned in a 1:1 ratio to one of two treatment arms. Both treatment arms will receive Quizartinib but at different doses. The study treatment is taken orally in 28 day cycles until either disease progression occurs or an unacceptable toxicity occurs. In addition to the study assessments to evaluate the disease, blood will be drawn to measure drug levels and biomarkers. Patients will be followed for survival at three month intervals after the end of treatment.
Interventions
DRUGAC220
oral
Sponsors
Ambit Biosciences Corporation
Daiichi Sankyo
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Subject has morphologically documented primary acute myeloid leukemia (AML) or AML secondary to myelodysplastic syndrome (MDS) as defined by the World Health Organization (WHO) criteria, as determined by pathology review at the treating institution and has relapsed or is refractory after 1 second line (salvage) regimen or after hematopoietic stem cell transplantation (HSCT) * Subject is positive for FLT3-ITD activating mutation in bone marrow or peripheral blood (\>10% allelic ratio) * Eastern Cooperative Oncology Group performance status of 0 to 2 * In the absence of rapidly progressing disease clearly documented by the investigator, the interval from prior treatment to time of AC220 administration will be at least 2 weeks (14 days) for prior cytotoxic agents or at least 5 half-lives for prior noncytotoxic agents, including immunosuppressive therapy post HSCT * Persistent chronic clinically significant nonhematological toxicities from prior treatment (including chemotherapy, kinase inhibitors, immunotherapy, experimental agents, radiation, HSCT, or surgery) must be Grade ≤ 1 * Patients - both males and females - with reproductive potential are eligible
Exclusion criteria
* Subject received previous treatment with AC220 * Subject has a diagnosis of acute promyelocytic leukemia * Subject has a diagnosis of chronic myelogenous leukemia (CML) in blast crisis * Subject has AML or antecedent MDS secondary to prior chemotherapy * Subject has had HSCT and has either of the following: * Donor lymphocyte infusion (DLI) is not permitted during the study or \< 30 days prior to study entry * Subject has clinically active central nervous system (CNS) leukemia. A subject is considered eligible if CNS leukemia is controlled and subject is receiving intrathecal (IT) therapy at study entry. Subjects should continue to receive IT therapy (or cranial radiation) as clinically indicated * Subject has received concurrent chemotherapy, immunotherapy, or radiotherapy within 14 days prior to the first dose of AC220, or any ancillary therapy that is considered to be investigational (i.e., used for non-approved indications(s) and in the context of a research investigation) within 30 days or 5 half-lives (whichever is longer) prior to the first dose of study drug * Subject requires treatment with concomitant drugs that prolong QT/QTc interval or with strong inhibitors or inducers of cytochrome P450- isozyme3A4 (CYP3A4) with the exception of antibiotics, antifungals, and antivirals that are used as standard of care post-transplant or to prevent or treat infections and other such drugs that are considered absolutely essential for the care of the subject * Subject requires treatment with anticoagulant therapy * Subject has a known positive test for human immunodeficiency virus, hepatitis C, or hepatitis B surface antigen * Subject had major surgery within 4 weeks prior to first dose of AC220 * Subject has uncontrolled or significant cardiovascular disease, including * Subject has a pre-existing disorder predisposing the subject to a serious or life-threatening infection (e.g. cystic fibrosis, congenital or acquired immunodeficiency, bleeding disorder, or cytopenias not related to AML) * Subject has an active uncontrolled acute or chronic systemic fungal, bacterial, viral, or other infection * Subject has any of the following laboratory values: * Subject is a female with a positive pregnancy test, pregnant, or breastfeeding * Subject has any medical, psychiatric, addictive or other kind of disorder which compromises the ability of the subject to give written informed consent and/or to comply with procedures
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Who Achieved Composite Complete Response (CRc) (Intent-to-Treat Population) | At end of Cycle 2 (after two complete 28-day cycles post treatment) | CRc is defined as Complete remission (CR) + Complete remission with incomplete platelet recovery (CRp) + Complete remission with incomplete hematological recovery (CRi). * Participants with CR must have normal hematopoietic cells and achieved a morphologic leukemia-free state (\<5% bone marrow blasts in bone marrow, no blasts with Auer rods and no persistence of extramedullary disease) and must have had an absolute neutrophil count (ANC) ≥1 × 10\^9/L and platelet count ≥100 × 10\^9/L and were red blood cell (RBC) and platelet transfusion independent. Blasts in the peripheral blood was to be ≤1% (if blood sample was available). * Participants with CRp must have achieved CR except for incomplete platelet recovery (\< 100 ×10\^9/L). * Participants with CRi must have fulfilled all the criteria for CR except for incomplete hematological recovery with residual neutropenia \<1 × 10\^9/L with or without complete platelet recovery. RBC and platelet transfusion independence were not required. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS) After Approximately 3 Years (Intent-to-Treat Population) | Evaluated at end of study, up to 6 months (approximately 3 years post treatment) | OS was defined as the time from the date of randomization until the date of death from any cause. |
| Event Free Survival (EFS) After Approximately 3 Years (Intent-to-Treat Population) | Evaluated at end of study, up to 6 months (approximately 3 years post treatment) | EFS was defined as the time from the date of randomization until the date of documented relapse or death. |
| Leukemia Free Survival (LFS) After Approximately 3 Years (Intent-to-Treat Population) | Evaluated at end of study, up to 6 months (approximately 3 years post treatment) | LFS was defined as the time from the date of first CRc until the date of documented relapse or death for participants who achieved CRc. |
| Number of Participants Who Achieved Complete Remission (CR) (Intent-to-Treat Population) | At end of treatment visit (approximately 3 years post treatment) | Participant must have bone marrow regenerating normal hematopoietic cells and achieve a morphologic leukemia-free state (\< 5% bone marrow blasts in bone marrow, no blasts with Auer rods and no persistence of extramedullary disease) and must have an absolute neutrophil count (ANC) ≥ 1x10\^9/L and platelet count ≥ 100 x 10\^9/L and they will be red blood cell (RBC) and platelet transfusion independent (defined as 4 weeks without RBC transfusions and 1 week without platelet transfusion). |
| Time to Composite Complete Remission (CRc) in Participants Who Achieved CRc After Approximately 3 Years (Intent-to-Treat Population) | Evaluated at end of study, up to 6 months (approximately 3 years post treatment) | Time to CRc was defined as the time from the date of randomization until the first disease assessment of CRc. Time to CRc was only evaluated in participants who achieved CRc. |
| Percentage of Participants Undergoing Hematopoietic Stem Cell Transplantation (HSCT) After Approximately 3 Years (Intent-to-Treat Population) | Evaluated at end of study, up to 6 months (approximately 3 years post treatment) | Transplantation rate was defined as the percentage of participants who underwent HSCT directly after treatment with quizartinib (no other intervening acute myeloid leukemia therapies other than conditioning regimens for the HSCT). |
| Percentage of Participants With Grade 2 or Higher QT Interval Corrected for Heart Rate Using Fridericia's Formula (QTcF) Prolongation After Receiving Quizartinib (Safety Analysis Set) | Evaluated at end of study, up to 6 months (approximately 3 years post treatment) | QT interval corrected for heart rate using Fridericia's formula (QTcF) grading was to be done according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 and the definition of Grade 2 or higher prolongation is QTcF more than 480 msec. |
| Duration of Remission After Approximately 3 Years (Intent-to-Treat Population) | Evaluated at end of study, up to 6 months (approximately 3 years post treatment) | Duration of remission was defined as the time from first documented remission until documented relapse. CRc was defined as composite complete remission and CRi was defined as complete remission with incomplete hematological recovery. |
Countries
France, Italy, United Kingdom, United States
Participant flow
Recruitment details
A total of 76 participants who met all inclusion criteria and no exclusion criteria were enrolled in the study (intent-to-treat population). Participants were enrolled at 22 clinic sites in North America and Europe (14 sites in the United States, 6 in France, 1 in Italy, and 1 in the United Kingdom).
Pre-assignment details
Participants were randomized (1:1) to receive 30 or 60 mg/day quizartinib. These doses were selected based on evidence of efficacy and safety observed in studies AC220-001 and AC220-002, and preclinical data.Two participants who were randomized to quizartinib (60 mg/day) did not receive study drug and are not included in the safety data.
Participants by arm
| Arm | Count |
|---|---|
| Quizartinib 30 mg Participants randomized to receive 30 mg quizartinib once daily. | 38 |
| Quizartinib 60 mg Participants were randomized to receive 60 mg quizartinib once daily. | 38 |
| Total | 76 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 6 | 1 |
| Overall Study | Death | 2 | 1 |
| Overall Study | HSCT Transplant | 11 | 15 |
| Overall Study | Lack of Efficacy | 4 | 2 |
| Overall Study | Participant went on Hospice Care | 1 | 0 |
| Overall Study | Progressive disease | 13 | 14 |
| Overall Study | Randomized, but never received drug | 0 | 2 |
| Overall Study | Withdrawal by Subject | 1 | 3 |
Baseline characteristics
| Characteristic | Quizartinib 30 mg | Total | Quizartinib 60 mg |
|---|---|---|---|
| Age, Continuous | 56.5 years | 54.5 years | 53.0 years |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 3 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 3 Participants | 2 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 | 7 Participants | 11 Participants | 4 Participants |
| Race (NIH/OMB) White | 29 Participants | 59 Participants | 30 Participants |
| Region of Enrollment France | 7 participants | 12 participants | 5 participants |
| Region of Enrollment Italy | 0 participants | 3 participants | 3 participants |
| Region of Enrollment United Kingdom | 2 participants | 3 participants | 1 participants |
| Region of Enrollment United States | 29 participants | 58 participants | 29 participants |
| Sex: Female, Male Female | 16 Participants | 32 Participants | 16 Participants |
| Sex: Female, Male Male | 22 Participants | 44 Participants | 22 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 9 / 38 | 13 / 36 |
| other Total, other adverse events | 37 / 38 | 36 / 36 |
| serious Total, serious adverse events | 25 / 38 | 23 / 36 |
Outcome results
Primary
Number of Participants Who Achieved Composite Complete Response (CRc) (Intent-to-Treat Population)
CRc is defined as Complete remission (CR) + Complete remission with incomplete platelet recovery (CRp) + Complete remission with incomplete hematological recovery (CRi). * Participants with CR must have normal hematopoietic cells and achieved a morphologic leukemia-free state (\<5% bone marrow blasts in bone marrow, no blasts with Auer rods and no persistence of extramedullary disease) and must have had an absolute neutrophil count (ANC) ≥1 × 10\^9/L and platelet count ≥100 × 10\^9/L and were red blood cell (RBC) and platelet transfusion independent. Blasts in the peripheral blood was to be ≤1% (if blood sample was available). * Participants with CRp must have achieved CR except for incomplete platelet recovery (\< 100 ×10\^9/L). * Participants with CRi must have fulfilled all the criteria for CR except for incomplete hematological recovery with residual neutropenia \<1 × 10\^9/L with or without complete platelet recovery. RBC and platelet transfusion independence were not required.
Time frame: At end of Cycle 2 (after two complete 28-day cycles post treatment)
Population: Composite complete remission was assessed in the intent-to-treat (ITT) analysis set.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Quizartinib 30 mg | Number of Participants Who Achieved Composite Complete Response (CRc) (Intent-to-Treat Population) | 18 Participants |
| Quizartinib 60 mg | Number of Participants Who Achieved Composite Complete Response (CRc) (Intent-to-Treat Population) | 18 Participants |
Secondary
Duration of Remission After Approximately 3 Years (Intent-to-Treat Population)
Duration of remission was defined as the time from first documented remission until documented relapse. CRc was defined as composite complete remission and CRi was defined as complete remission with incomplete hematological recovery.
Time frame: Evaluated at end of study, up to 6 months (approximately 3 years post treatment)
Population: Duration of remission was assessed in the intent-to-treat (ITT) analysis set.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Quizartinib 30 mg | Duration of Remission After Approximately 3 Years (Intent-to-Treat Population) | CRc | 4.2 weeks |
| Quizartinib 30 mg | Duration of Remission After Approximately 3 Years (Intent-to-Treat Population) | CRi | 4.1 weeks |
| Quizartinib 60 mg | Duration of Remission After Approximately 3 Years (Intent-to-Treat Population) | CRc | 9.1 weeks |
| Quizartinib 60 mg | Duration of Remission After Approximately 3 Years (Intent-to-Treat Population) | CRi | 20.0 weeks |
Secondary
Event Free Survival (EFS) After Approximately 3 Years (Intent-to-Treat Population)
EFS was defined as the time from the date of randomization until the date of documented relapse or death.
Time frame: Evaluated at end of study, up to 6 months (approximately 3 years post treatment)
Population: EFS was assessed in the intent-to-treat (ITT) analysis set.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Quizartinib 30 mg | Event Free Survival (EFS) After Approximately 3 Years (Intent-to-Treat Population) | 12.0 weeks |
| Quizartinib 60 mg | Event Free Survival (EFS) After Approximately 3 Years (Intent-to-Treat Population) | 13.7 weeks |
Secondary
Leukemia Free Survival (LFS) After Approximately 3 Years (Intent-to-Treat Population)
LFS was defined as the time from the date of first CRc until the date of documented relapse or death for participants who achieved CRc.
Time frame: Evaluated at end of study, up to 6 months (approximately 3 years post treatment)
Population: LFS was assessed in the intent-to-treat (ITT) analysis set.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Quizartinib 30 mg | Leukemia Free Survival (LFS) After Approximately 3 Years (Intent-to-Treat Population) | 4.1 weeks |
| Quizartinib 60 mg | Leukemia Free Survival (LFS) After Approximately 3 Years (Intent-to-Treat Population) | 9.1 weeks |
Secondary
Number of Participants Who Achieved Complete Remission (CR) (Intent-to-Treat Population)
Participant must have bone marrow regenerating normal hematopoietic cells and achieve a morphologic leukemia-free state (\< 5% bone marrow blasts in bone marrow, no blasts with Auer rods and no persistence of extramedullary disease) and must have an absolute neutrophil count (ANC) ≥ 1x10\^9/L and platelet count ≥ 100 x 10\^9/L and they will be red blood cell (RBC) and platelet transfusion independent (defined as 4 weeks without RBC transfusions and 1 week without platelet transfusion).
Time frame: At end of treatment visit (approximately 3 years post treatment)
Population: Complete remission was assessed in the intent-to-treat (ITT) analysis set.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Quizartinib 30 mg | Number of Participants Who Achieved Complete Remission (CR) (Intent-to-Treat Population) | 2 Participants |
| Quizartinib 60 mg | Number of Participants Who Achieved Complete Remission (CR) (Intent-to-Treat Population) | 1 Participants |
Secondary
Overall Survival (OS) After Approximately 3 Years (Intent-to-Treat Population)
OS was defined as the time from the date of randomization until the date of death from any cause.
Time frame: Evaluated at end of study, up to 6 months (approximately 3 years post treatment)
Population: OS was assessed in the intent-to-treat (ITT) analysis set.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Quizartinib 30 mg | Overall Survival (OS) After Approximately 3 Years (Intent-to-Treat Population) | 20.9 weeks |
| Quizartinib 60 mg | Overall Survival (OS) After Approximately 3 Years (Intent-to-Treat Population) | 27.3 weeks |
Secondary
Percentage of Participants Undergoing Hematopoietic Stem Cell Transplantation (HSCT) After Approximately 3 Years (Intent-to-Treat Population)
Transplantation rate was defined as the percentage of participants who underwent HSCT directly after treatment with quizartinib (no other intervening acute myeloid leukemia therapies other than conditioning regimens for the HSCT).
Time frame: Evaluated at end of study, up to 6 months (approximately 3 years post treatment)
Population: Transplantation rate was assessed in the intent-to-treat (ITT) analysis set.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Quizartinib 30 mg | Percentage of Participants Undergoing Hematopoietic Stem Cell Transplantation (HSCT) After Approximately 3 Years (Intent-to-Treat Population) | Yes | 31.6 percentage of participants |
| Quizartinib 30 mg | Percentage of Participants Undergoing Hematopoietic Stem Cell Transplantation (HSCT) After Approximately 3 Years (Intent-to-Treat Population) | No | 68.4 percentage of participants |
| Quizartinib 30 mg | Percentage of Participants Undergoing Hematopoietic Stem Cell Transplantation (HSCT) After Approximately 3 Years (Intent-to-Treat Population) | Unknown | 0 percentage of participants |
| Quizartinib 60 mg | Percentage of Participants Undergoing Hematopoietic Stem Cell Transplantation (HSCT) After Approximately 3 Years (Intent-to-Treat Population) | Yes | 42.1 percentage of participants |
| Quizartinib 60 mg | Percentage of Participants Undergoing Hematopoietic Stem Cell Transplantation (HSCT) After Approximately 3 Years (Intent-to-Treat Population) | No | 55.3 percentage of participants |
| Quizartinib 60 mg | Percentage of Participants Undergoing Hematopoietic Stem Cell Transplantation (HSCT) After Approximately 3 Years (Intent-to-Treat Population) | Unknown | 2.6 percentage of participants |
Secondary
Percentage of Participants With Grade 2 or Higher QT Interval Corrected for Heart Rate Using Fridericia's Formula (QTcF) Prolongation After Receiving Quizartinib (Safety Analysis Set)
QT interval corrected for heart rate using Fridericia's formula (QTcF) grading was to be done according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 and the definition of Grade 2 or higher prolongation is QTcF more than 480 msec.
Time frame: Evaluated at end of study, up to 6 months (approximately 3 years post treatment)
Population: QTcF prolongation was assessed in the Safety Analysis Set.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Quizartinib 30 mg | Percentage of Participants With Grade 2 or Higher QT Interval Corrected for Heart Rate Using Fridericia's Formula (QTcF) Prolongation After Receiving Quizartinib (Safety Analysis Set) | Max on study; >500 msec | 5.3 percentage of participants |
| Quizartinib 30 mg | Percentage of Participants With Grade 2 or Higher QT Interval Corrected for Heart Rate Using Fridericia's Formula (QTcF) Prolongation After Receiving Quizartinib (Safety Analysis Set) | Max on study; <450 msec | 47.4 percentage of participants |
| Quizartinib 30 mg | Percentage of Participants With Grade 2 or Higher QT Interval Corrected for Heart Rate Using Fridericia's Formula (QTcF) Prolongation After Receiving Quizartinib (Safety Analysis Set) | Max change from baseline; ≤30 msec | 47.4 percentage of participants |
| Quizartinib 30 mg | Percentage of Participants With Grade 2 or Higher QT Interval Corrected for Heart Rate Using Fridericia's Formula (QTcF) Prolongation After Receiving Quizartinib (Safety Analysis Set) | Max change from baseline; >30 msec and ≤60 msec | 47.4 percentage of participants |
| Quizartinib 30 mg | Percentage of Participants With Grade 2 or Higher QT Interval Corrected for Heart Rate Using Fridericia's Formula (QTcF) Prolongation After Receiving Quizartinib (Safety Analysis Set) | Max on study; >480 msec and ≤500 msec | 5.3 percentage of participants |
| Quizartinib 30 mg | Percentage of Participants With Grade 2 or Higher QT Interval Corrected for Heart Rate Using Fridericia's Formula (QTcF) Prolongation After Receiving Quizartinib (Safety Analysis Set) | Max change from baseline; >60 msec | 5.3 percentage of participants |
| Quizartinib 30 mg | Percentage of Participants With Grade 2 or Higher QT Interval Corrected for Heart Rate Using Fridericia's Formula (QTcF) Prolongation After Receiving Quizartinib (Safety Analysis Set) | Max on study; ≥450 msec and ≤480 msec | 42.1 percentage of participants |
| Quizartinib 60 mg | Percentage of Participants With Grade 2 or Higher QT Interval Corrected for Heart Rate Using Fridericia's Formula (QTcF) Prolongation After Receiving Quizartinib (Safety Analysis Set) | Max change from baseline; >60 msec | 19.4 percentage of participants |
| Quizartinib 60 mg | Percentage of Participants With Grade 2 or Higher QT Interval Corrected for Heart Rate Using Fridericia's Formula (QTcF) Prolongation After Receiving Quizartinib (Safety Analysis Set) | Max on study; <450 msec | 36.1 percentage of participants |
| Quizartinib 60 mg | Percentage of Participants With Grade 2 or Higher QT Interval Corrected for Heart Rate Using Fridericia's Formula (QTcF) Prolongation After Receiving Quizartinib (Safety Analysis Set) | Max on study; ≥450 msec and ≤480 msec | 47.2 percentage of participants |
| Quizartinib 60 mg | Percentage of Participants With Grade 2 or Higher QT Interval Corrected for Heart Rate Using Fridericia's Formula (QTcF) Prolongation After Receiving Quizartinib (Safety Analysis Set) | Max on study; >480 msec and ≤500 msec | 13.9 percentage of participants |
| Quizartinib 60 mg | Percentage of Participants With Grade 2 or Higher QT Interval Corrected for Heart Rate Using Fridericia's Formula (QTcF) Prolongation After Receiving Quizartinib (Safety Analysis Set) | Max on study; >500 msec | 2.8 percentage of participants |
| Quizartinib 60 mg | Percentage of Participants With Grade 2 or Higher QT Interval Corrected for Heart Rate Using Fridericia's Formula (QTcF) Prolongation After Receiving Quizartinib (Safety Analysis Set) | Max change from baseline; >30 msec and ≤60 msec | 41.7 percentage of participants |
| Quizartinib 60 mg | Percentage of Participants With Grade 2 or Higher QT Interval Corrected for Heart Rate Using Fridericia's Formula (QTcF) Prolongation After Receiving Quizartinib (Safety Analysis Set) | Max change from baseline; ≤30 msec | 38.9 percentage of participants |
Secondary
Time to Composite Complete Remission (CRc) in Participants Who Achieved CRc After Approximately 3 Years (Intent-to-Treat Population)
Time to CRc was defined as the time from the date of randomization until the first disease assessment of CRc. Time to CRc was only evaluated in participants who achieved CRc.
Time frame: Evaluated at end of study, up to 6 months (approximately 3 years post treatment)
Population: Time to CRc was assessed in the intent-to-treat (ITT) analysis set.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Quizartinib 30 mg | Time to Composite Complete Remission (CRc) in Participants Who Achieved CRc After Approximately 3 Years (Intent-to-Treat Population) | 4.4 weeks |
| Quizartinib 60 mg | Time to Composite Complete Remission (CRc) in Participants Who Achieved CRc After Approximately 3 Years (Intent-to-Treat Population) | 4.6 weeks |