Acute Myeloid Leukemia
Conditions
Keywords
AML
Brief summary
This Phase 3 study assesses two drug regimens as the initial treatment of patients who are at least 70 years of age and have newly diagnosed acute myeloid leukemia (AML) for whom the doctor does not recommend the use of standard intensive treatment or the patient has decided not to receive standard intensive treatment after being fully informed about its benefits and risks by his/her doctor. The two drug regimens are sapacitabine administered in alternating cycles with decitabine or decitabine alone. The purpose of the study is to learn which drug regimen is more likely to keep AML in check as long as possible.
Detailed description
This is a multicenter, randomized, Phase 3 study (SEAMLESS) comparing two drug regimens (arms) as the front-line treatment of elderly patients aged 70 years or older with newly diagnosed acute myeloid leukemia (AML) who are not candidates for intensive induction chemotherapy. In Arm A, sapacitabine is administered in alternating cycles with decitabine, and in Arm C decitabine is administered alone. The primary efficacy endpoint is overall survival. The study is designed to demonstrate an improvement in overall survival of Arm A versus Arm C.
Interventions
DRUGSapacitabine
Oral sapacitabine capsules
DRUGDecitabine
Decitabine intravenous
Sponsors
Cyclacel Pharmaceuticals, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
70 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Newly diagnosed AML based on WHO (World Health Organization) classification * Age 70 years or older for whom the treatment of choice is low-intensity therapy by investigator assessment or who has refused intensive induction therapy recommended by investigator * ECOG (Eastern Cooperative Oncology Group) performance status 0-2 * Adequate renal function * Adequate liver function * Able to swallow capsules * Agree to practice effective contraception * Ability to understand and willingness to sign the informed consent form
Exclusion criteria
* AML is of the sub-type of acute promyelocytic leukemia or extramedullary myeloid tumor without bone marrow involvement * Having received any systemic anti-cancer therapy for AML or received treatment with hypomethylating agents or cytotoxic chemotherapy for preceding myelodysplastic syndrome (MDS) or myeloproliferative disease (MPD) * Known or suspected central nervous system (CNS) involvement by leukemia * Uncontrolled intercurrent illness * Known hypersensitivity to decitabine * Known to be HIV-positive
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival | up to 43 months | The distribution of overall survival was estimated by the method of Kaplan and Meier. A log-rank analysis stratified by randomization stratification factors was used to compare overall survival between Arm A (decitabine/sapacitabine) versus Arm C (decitabine). Cox proportional hazards models were used to identify predictive factors for overall survival. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Complete Remission (CR) | up to 43 months | Normalization of peripheral neutrophils to \>=1000 /microliter, platelet to \>=100,000/microliter within 2 weeks of bone marrow biopsy/aspirate, and bone marrow to \<=5 % blasts; independent of transfusions\*; and no extramedullary leukemia. \* independent of transfusions refer to no platelet transfusion for 1 week prior to achieving the response |
| Complete Remission With Incomplete Platelet Count Recovery (CRp) | up to 43 months | Normalization of bone marrow to \<=5% blasts; peripheral neutrophils \>=1000 /microliter, platelet \<=100,000 /microliter within 2 weeks of bone marrow biopsy/aspirate; independent of transfusions\*; and no extramedullary leukemia. \*independent of transfusions refer to no platelet transfusion for 1 week prior to achieving the response |
| Partial Remission (PR) | up to 43 months | Normalization of peripheral neutrophils to \>=1000 /microliter, platelet to \>=100,000/microliter within 2 weeks of bone marrow biopsy/aspirate, \>=50% decrease in bone marrow blasts over pre-treatment but still \>5%; independent of transfusions\* \*independent of transfusions refer to no platelet transfusion for 1 week prior to achieving the response |
| Hematological Improvement | up to 43 months | HI with duration (HI) 1. Erythroid response (HI-E) for patients with pre-treatment hemoglobin \< 11 g/dL; Major response: \>2 g/dL increase in hemoglobin; for RBC, transfusion independence\* Minor response: 1 to 2 g/dL increase in hemoglobin; for RBC, a 50% decrease in transfusion requirements 2. Platelet response (HI-P) for pre-treatment platelet count \<100,000/mm3; Major response: an absolute increase of platelet count by \>=30,000/mm3; stabilization of platelet counts and platelet transfusion independence\* Minor response: \>=50% increase in platelet count with a net increase \> 10,000/mm3 but \<30,000/mm3 3. Neutrophil response (HI-N) for absolute neutrophil count (ANC) \< 1,500/mm3 before therapy; Major response: \>=100% increase, or an absolute increase of \>500/mm3, whichever is greater Minor response: \>=100% increase, but absolute increase \< 500/mm3 * independent of transfusions refer to no platelet transfusion for 1 week prior to achieving the response |
| Blood Products Transfused | up to 43 months | Number of units of packed red blood cells (PRBC) and/or platelet transfusions administered per 8-week period prior to the first dose of study drug and through the date of treatment discontinuation. |
| Hospitalized Days | up to 12 months | In-patient days in hospital. |
| Stable Disease (SD) | up to 43 months | Failure to achieve at least hematologic improvement (HI), but no evidence of clinically significant progression for \> 16 weeks. |
| Duration of Complete Remission (dCR) | up to 43 months | Durations of normalization of peripheral neutrophils to \>=1000 /microliter, platelet to \>=100,000/microliter within 2 weeks of bone marrow biopsy/aspirate, and bone marrow to \<=5 % blasts; independent of transfusions\*; and no extramedullary leukemia. \* independent of transfusions refer to no platelet transfusion for 1 week prior to achieving the response |
| Duration of Complete Remission With Incomplete Platelet Count Recovery (dCRp) | up to 43 months | Duration of normalization of bone marrow to \<=5% blasts; peripheral neutrophils \>=1000 /microliter, platelet \<=100,000 /microliter within 2 weeks of bone marrow biopsy/aspirate; independent of transfusions\*; and no extramedullary leukemia. \*independent of transfusions refer to no platelet transfusion for 1 week prior to achieving the response |
| Duration of Partial Remission (dPR) | up to 43 months | Duration of normalization of peripheral neutrophils to \>=1000 /microliter, platelet to \>=100,000/microliter within 2 weeks of bone marrow biopsy/aspirate, \>=50% decrease in bone marrow blasts over pre-treatment but still \>5%; independent of transfusions\* \*independent of transfusions refer to no platelet transfusion for 1 week prior to achieving the response |
| Duration of Hematological Improvement (dHI) | up to 43 months | Duration of HI 1. Erythroid response (HI-E) for patients with pre-treatment hemoglobin \< 11 g/dL; Major response: \>2 g/dL increase in hemoglobin; for RBC, transfusion independence\* Minor response: 1 to 2 g/dL increase in hemoglobin; for RBC, a 50% decrease in transfusion requirements 2. Platelet response (HI-P) for pre-treatment platelet count \<100,000/mm3; Major response: an absolute increase of platelet count by \>=30,000/mm3; stabilization of platelet counts and platelet transfusion independence\* Minor response: \>=50% increase in platelet count with a net increase \> 10,000/mm3 but \<30,000/mm3 3. Neutrophil response (HI-N) for absolute neutrophil count (ANC) \< 1,500/mm3 before therapy; Major response: \>=100% increase, or an absolute increase of \>500/mm3, whichever is greater Minor response: \>=100% increase, but absolute increase \< 500/mm3 * independent of transfusions refer to no platelet transfusion for 1 week prior to achieving the response |
| Duration of Stable Disease (dSD) | up to 43 months | Failure to achieve at least hematologic improvement (HI), but no evidence of clinically significant progression for \> 16 weeks. |
| 1-year Survival | Percentage of patients alive at 1 year after randomization (participants were assessed up to 43 months for overall survival curve estimation but this measure presents the 1 year survival rate percentage). | One-year survival is the percentage of patients who are alive at 1-year measured from the date of randomization. |
Countries
Austria, Belgium, France, Germany, Hungary, Italy, Poland, Spain, Sweden, Switzerland, United Kingdom, United States
Participant flow
Pre-assignment details
The study comprised a single-arm Lead-in phase to confirm the safety and tolerability of administering sapacitabine in alternating cycles with decitabine prior to patients being enrolled in the parallel group, randomized Phase III phase to compare the two treatment arms. 21 patients were enrolled in the Lead-in phase.
Participants by arm
| Arm | Count |
|---|---|
| Sapacitabine-decitabine Alternating Arm A sapacitabine administered in alternating cycles with decitabine
Sapacitabine: Oral sapacitabine capsules
Decitabine: Decitabine intravenous | 241 |
| Decitabine Arm C Decitabine
Decitabine: Decitabine intravenous | 241 |
| Total | 482 |
Baseline characteristics
| Characteristic | Sapacitabine-decitabine Alternating | Decitabine | Total |
|---|---|---|---|
| Age, Continuous | 78 years | 77 years | 77 years |
| Race/Ethnicity, Customized American Indian or Alaska Native | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Asian or Pacific Islander | 1 Participants | 3 Participants | 4 Participants |
| Race/Ethnicity, Customized Black | 6 Participants | 17 Participants | 23 Participants |
| Race/Ethnicity, Customized Caucasian | 212 Participants | 194 Participants | 406 Participants |
| Race/Ethnicity, Customized Hispanic | 6 Participants | 3 Participants | 9 Participants |
| Race/Ethnicity, Customized Other | 2 Participants | 3 Participants | 5 Participants |
| Race/Ethnicity, Customized Unknown | 13 Participants | 21 Participants | 34 Participants |
| Sex: Female, Male Female | 102 Participants | 95 Participants | 197 Participants |
| Sex: Female, Male Male | 139 Participants | 146 Participants | 285 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 21 / 21 | 221 / 241 | 211 / 241 |
| other Total, other adverse events | 0 / 0 | 236 / 236 | 232 / 233 |
| serious Total, serious adverse events | 17 / 21 | 199 / 236 | 188 / 233 |
Outcome results
Primary
Overall Survival
The distribution of overall survival was estimated by the method of Kaplan and Meier. A log-rank analysis stratified by randomization stratification factors was used to compare overall survival between Arm A (decitabine/sapacitabine) versus Arm C (decitabine). Cox proportional hazards models were used to identify predictive factors for overall survival.
Time frame: up to 43 months
Population: Patients \>= 70 years with histologically or pathologically confirmed AML; not treated by systemic therapy; on low-intensity therapy by investigator assessment or the patient has refused standard induction chemotherapy; no prior treatment with HMA or other anti-cancer agents; ECOG status 0-2; adequate hepatic and renal function
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Sapacitabine-decitabine Alternating | Overall Survival | 5.9 Months |
| Decitabine | Overall Survival | 5.7 Months |
Comparison: The phase III part planned to randomize 485 patients, about 243 per arm (actual 241 patients per arm), over an estimated period of 24 months. Final analysis would occur at approximately 424 deaths, which was expected to be observed about 43 months after the accrual of the first patient. A stratified log rank analysis would have 90% power to detect a 27.5% reduction in the risk of death, i.e., a hazard ratio of 0.725, between Arm A and Arm C.p-value: <0.024995% CI: [0.837, 1.226]Kaplan-Meier
Comparison: Subgroup analyses (pre-specified): Presence of antecedent MDS or MPD (covariate)~Treatment covariate: alternating sapacitabine/decitabine treatment Levels: No (i.e., de novo) vs Presence of antecedent MDS or MPDp-value: <0.024995% CI: [0.86, 1.35]Log Rank
Comparison: Subgroup analyses (pre-specified): Baseline peripheral WBC count ≥ 10 x 109/L (covariate)~Treatment covariate: alternating sapacitabine/decitabine treatment Levels: Baseline WBC count ≥ 10 x 109/L vs WBC count ≤ 10 x 109/Lp-value: <0.024995% CI: [1.12, 2.19]Log Rank
Comparison: Subgroup analyses (pre-specified): Baseline bone marrow blast percentage ≥ 50% (covariate)~Treatment covariate: alternating sapacitabine/decitabine treatment Levels: Baseline bone marrow blast percentage ≥ 50% vs Blast percentage ≤ 50%p-value: <0.024995% CI: [0.77, 1.32]Log Rank
Comparison: Subgroup analyses (pre-specified): Unfavorable cytogenetics risk by SWOG (covariate)~Treatment covariate: alternating sapacitabine/decitabine treatment Levels: Unfavorable cytogenetics vs otherp-value: <0.024995% CI: [0.94, 1.73]Log Rank
Comparison: Subgroup analyses (post-hoc): Region (covariate)~Treatment covariate: alternating sapacitabine/decitabine treatment (Arm A) Levels: EU vs USp-value: <0.0249Log Rank
Comparison: Subgroup analyses (post-hoc): Age (covariate)~Treatment covariate: alternating sapacitabine/decitabine treatment (Arm A) Levels: ≥ 75 years old vs ≤ 75 years oldp-value: <0.0249Log Rank
Comparison: Subgroup analyses (post-hoc): Gender (covariate)~Treatment covariate: alternating sapacitabine/decitabine treatment (Arm A) Levels: Male vs Femalep-value: <0.0249Log Rank
Comparison: Subgroup analyses (post-hoc): ECOG status (covariate)~Treatment covariate: alternating sapacitabine/decitabine treatment (Arm A) Levels: Status 2 vs \< 2p-value: <0.0249Log Rank
Comparison: Subgroup analyses (post-hoc): HCT-CI score (covariate)~Treatment covariate: alternating sapacitabine/decitabine treatment Levels: HCT-CI score 0-2 vs HCT-CI score \>2p-value: <0.0249Log Rank
Secondary
1-year Survival
One-year survival is the percentage of patients who are alive at 1-year measured from the date of randomization.
Time frame: Percentage of patients alive at 1 year after randomization (participants were assessed up to 43 months for overall survival curve estimation but this measure presents the 1 year survival rate percentage).
Population: Patients \>= 70 years with histologically or pathologically confirmed AML; not treated by systemic therapy; on low-intensity therapy by investigator assessment or the patient has refused standard induction chemotherapy; no prior treatment with HMA or other anti-cancer agents; ECOG status 0-2; adequate hepatic and renal function.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Sapacitabine-decitabine Alternating | 1-year Survival | 81 Participants |
| Decitabine | 1-year Survival | 83 Participants |
p-value: <0.024995% CI: [0.837, 1.226]Log Rank
Secondary
Blood Products Transfused
Number of units of packed red blood cells (PRBC) and/or platelet transfusions administered per 8-week period prior to the first dose of study drug and through the date of treatment discontinuation.
Time frame: up to 43 months
Population: Patients \>= 70 years with histologically or pathologically confirmed AML; not treated by systemic therapy; on low-intensity therapy by investigator assessment or the patient has refused standard induction chemotherapy; no prior treatment with HMA or other anti-cancer agents; ECOG status 0-2; adequate hepatic and renal function
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Sapacitabine-decitabine Alternating | Blood Products Transfused | 20 Pint |
| Decitabine | Blood Products Transfused | 14 Pint |
p-value: 0.0416Wilcoxon (Mann-Whitney)
Secondary
Complete Remission (CR)
Normalization of peripheral neutrophils to \>=1000 /microliter, platelet to \>=100,000/microliter within 2 weeks of bone marrow biopsy/aspirate, and bone marrow to \<=5 % blasts; independent of transfusions\*; and no extramedullary leukemia. \* independent of transfusions refer to no platelet transfusion for 1 week prior to achieving the response
Time frame: up to 43 months
Population: Patients \>= 70 years with histologically or pathologically confirmed AML; not treated by systemic therapy; on low-intensity therapy by investigator assessment or the patient has refused standard induction chemotherapy; no prior treatment with HMA or other anti-cancer agents; ECOG status 0-2; adequate hepatic and renal function
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Sapacitabine-decitabine Alternating | Complete Remission (CR) | Responders | 40 Participants |
| Sapacitabine-decitabine Alternating | Complete Remission (CR) | Non-Responders | 198 Participants |
| Sapacitabine-decitabine Alternating | Complete Remission (CR) | Missing | 3 Participants |
| Decitabine | Complete Remission (CR) | Responders | 26 Participants |
| Decitabine | Complete Remission (CR) | Non-Responders | 213 Participants |
| Decitabine | Complete Remission (CR) | Missing | 2 Participants |
p-value: 0.146895% CI: [0.645, 2.782]Fisher Exact
Secondary
Complete Remission With Incomplete Platelet Count Recovery (CRp)
Normalization of bone marrow to \<=5% blasts; peripheral neutrophils \>=1000 /microliter, platelet \<=100,000 /microliter within 2 weeks of bone marrow biopsy/aspirate; independent of transfusions\*; and no extramedullary leukemia. \*independent of transfusions refer to no platelet transfusion for 1 week prior to achieving the response
Time frame: up to 43 months
Population: Patients \>= 70 years with histologically or pathologically confirmed AML; not treated by systemic therapy; on low-intensity therapy by investigator assessment or the patient has refused standard induction chemotherapy; no prior treatment with HMA or other anti-cancer agents; ECOG status 0-2; adequate hepatic and renal function
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Sapacitabine-decitabine Alternating | Complete Remission With Incomplete Platelet Count Recovery (CRp) | Responders | 5 Participants |
| Sapacitabine-decitabine Alternating | Complete Remission With Incomplete Platelet Count Recovery (CRp) | Non-Responders | 233 Participants |
| Sapacitabine-decitabine Alternating | Complete Remission With Incomplete Platelet Count Recovery (CRp) | Missing | 3 Participants |
| Decitabine | Complete Remission With Incomplete Platelet Count Recovery (CRp) | Responders | 5 Participants |
| Decitabine | Complete Remission With Incomplete Platelet Count Recovery (CRp) | Non-Responders | 234 Participants |
| Decitabine | Complete Remission With Incomplete Platelet Count Recovery (CRp) | Missing | 2 Participants |
Secondary
Duration of Complete Remission (dCR)
Durations of normalization of peripheral neutrophils to \>=1000 /microliter, platelet to \>=100,000/microliter within 2 weeks of bone marrow biopsy/aspirate, and bone marrow to \<=5 % blasts; independent of transfusions\*; and no extramedullary leukemia. \* independent of transfusions refer to no platelet transfusion for 1 week prior to achieving the response
Time frame: up to 43 months
Population: Patients \>= 70 years with histologically or pathologically confirmed AML; not treated by systemic therapy; on low-intensity therapy by investigator assessment or the patient has refused standard induction chemotherapy; no prior treatment with HMA or other anti-cancer agents; ECOG status 0-2; adequate hepatic and renal function
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Sapacitabine-decitabine Alternating | Duration of Complete Remission (dCR) | 9.5 months |
| Decitabine | Duration of Complete Remission (dCR) | 10.4 months |
Secondary
Duration of Complete Remission With Incomplete Platelet Count Recovery (dCRp)
Duration of normalization of bone marrow to \<=5% blasts; peripheral neutrophils \>=1000 /microliter, platelet \<=100,000 /microliter within 2 weeks of bone marrow biopsy/aspirate; independent of transfusions\*; and no extramedullary leukemia. \*independent of transfusions refer to no platelet transfusion for 1 week prior to achieving the response
Time frame: up to 43 months
Population: Patients \>= 70 years with histologically or pathologically confirmed AML; not treated by systemic therapy; on low-intensity therapy by investigator assessment or the patient has refused standard induction chemotherapy; no prior treatment with HMA or other anti-cancer agents; ECOG status 0-2; adequate hepatic and renal function
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Sapacitabine-decitabine Alternating | Duration of Complete Remission With Incomplete Platelet Count Recovery (dCRp) | 9.5 months |
| Decitabine | Duration of Complete Remission With Incomplete Platelet Count Recovery (dCRp) | 5.7 months |
Secondary
Duration of Hematological Improvement (dHI)
Duration of HI 1. Erythroid response (HI-E) for patients with pre-treatment hemoglobin \< 11 g/dL; Major response: \>2 g/dL increase in hemoglobin; for RBC, transfusion independence\* Minor response: 1 to 2 g/dL increase in hemoglobin; for RBC, a 50% decrease in transfusion requirements 2. Platelet response (HI-P) for pre-treatment platelet count \<100,000/mm3; Major response: an absolute increase of platelet count by \>=30,000/mm3; stabilization of platelet counts and platelet transfusion independence\* Minor response: \>=50% increase in platelet count with a net increase \> 10,000/mm3 but \<30,000/mm3 3. Neutrophil response (HI-N) for absolute neutrophil count (ANC) \< 1,500/mm3 before therapy; Major response: \>=100% increase, or an absolute increase of \>500/mm3, whichever is greater Minor response: \>=100% increase, but absolute increase \< 500/mm3 * independent of transfusions refer to no platelet transfusion for 1 week prior to achieving the response
Time frame: up to 43 months
Population: Patients \>= 70 years with histologically or pathologically confirmed AML; not treated by systemic therapy; on low-intensity therapy by investigator assessment or the patient has refused standard induction chemotherapy; no prior treatment with HMA or other anti-cancer agents; ECOG status 0-2; adequate hepatic and renal function
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Sapacitabine-decitabine Alternating | Duration of Hematological Improvement (dHI) | 5.8 months |
| Decitabine | Duration of Hematological Improvement (dHI) | 4.8 months |
Secondary
Duration of Partial Remission (dPR)
Duration of normalization of peripheral neutrophils to \>=1000 /microliter, platelet to \>=100,000/microliter within 2 weeks of bone marrow biopsy/aspirate, \>=50% decrease in bone marrow blasts over pre-treatment but still \>5%; independent of transfusions\* \*independent of transfusions refer to no platelet transfusion for 1 week prior to achieving the response
Time frame: up to 43 months
Population: Patients \>= 70 years with histologically or pathologically confirmed AML; not treated by systemic therapy; on low-intensity therapy by investigator assessment or the patient has refused standard induction chemotherapy; no prior treatment with HMA or other anti-cancer agents; ECOG status 0-2; adequate hepatic and renal function
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Sapacitabine-decitabine Alternating | Duration of Partial Remission (dPR) | 2.2 months |
| Decitabine | Duration of Partial Remission (dPR) | 1.9 months |
Secondary
Duration of Stable Disease (dSD)
Failure to achieve at least hematologic improvement (HI), but no evidence of clinically significant progression for \> 16 weeks.
Time frame: up to 43 months
Population: Patients \>= 70 years with histologically or pathologically confirmed AML; not treated by systemic therapy; on low-intensity therapy by investigator assessment or the patient has refused standard induction chemotherapy; no prior treatment with HMA or other anti-cancer agents; ECOG status 0-2; adequate hepatic and renal function
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Sapacitabine-decitabine Alternating | Duration of Stable Disease (dSD) | 23.3 months |
| Decitabine | Duration of Stable Disease (dSD) | 14.8 months |
Secondary
Hematological Improvement
HI with duration (HI) 1. Erythroid response (HI-E) for patients with pre-treatment hemoglobin \< 11 g/dL; Major response: \>2 g/dL increase in hemoglobin; for RBC, transfusion independence\* Minor response: 1 to 2 g/dL increase in hemoglobin; for RBC, a 50% decrease in transfusion requirements 2. Platelet response (HI-P) for pre-treatment platelet count \<100,000/mm3; Major response: an absolute increase of platelet count by \>=30,000/mm3; stabilization of platelet counts and platelet transfusion independence\* Minor response: \>=50% increase in platelet count with a net increase \> 10,000/mm3 but \<30,000/mm3 3. Neutrophil response (HI-N) for absolute neutrophil count (ANC) \< 1,500/mm3 before therapy; Major response: \>=100% increase, or an absolute increase of \>500/mm3, whichever is greater Minor response: \>=100% increase, but absolute increase \< 500/mm3 * independent of transfusions refer to no platelet transfusion for 1 week prior to achieving the response
Time frame: up to 43 months
Population: Patients \>= 70 years with histologically or pathologically confirmed AML; not treated by systemic therapy; on low-intensity therapy by investigator assessment or the patient has refused standard induction chemotherapy; no prior treatment with HMA or other anti-cancer agents; ECOG status 0-2; adequate hepatic and renal function
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Sapacitabine-decitabine Alternating | Hematological Improvement | Responders | 41 Participants |
| Sapacitabine-decitabine Alternating | Hematological Improvement | Non-Responders | 197 Participants |
| Sapacitabine-decitabine Alternating | Hematological Improvement | Missing | 3 Participants |
| Decitabine | Hematological Improvement | Responders | 38 Participants |
| Decitabine | Hematological Improvement | Non-Responders | 201 Participants |
| Decitabine | Hematological Improvement | Missing | 2 Participants |
Secondary
Hospitalized Days
In-patient days in hospital.
Time frame: up to 12 months
Population: Patients \>= 70 years with histologically or pathologically confirmed AML; not treated by systemic therapy; on low-intensity therapy by investigator assessment or the patient has refused standard induction chemotherapy; no prior treatment with HMA or other anti-cancer agents; ECOG status 0-2; adequate hepatic and renal function
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Sapacitabine-decitabine Alternating | Hospitalized Days | 15 Days |
| Decitabine | Hospitalized Days | 14 Days |
p-value: 0.1568Wilcoxon (Mann-Whitney)
Secondary
Partial Remission (PR)
Normalization of peripheral neutrophils to \>=1000 /microliter, platelet to \>=100,000/microliter within 2 weeks of bone marrow biopsy/aspirate, \>=50% decrease in bone marrow blasts over pre-treatment but still \>5%; independent of transfusions\* \*independent of transfusions refer to no platelet transfusion for 1 week prior to achieving the response
Time frame: up to 43 months
Population: Patients \>= 70 years with histologically or pathologically confirmed AML; not treated by systemic therapy; on low-intensity therapy by investigator assessment or the patient has refused standard induction chemotherapy; no prior treatment with HMA or other anti-cancer agents; ECOG status 0-2; adequate hepatic and renal function
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Sapacitabine-decitabine Alternating | Partial Remission (PR) | Missing | 3 Participants |
| Sapacitabine-decitabine Alternating | Partial Remission (PR) | Responders | 12 Participants |
| Sapacitabine-decitabine Alternating | Partial Remission (PR) | Non-Responders | 226 Participants |
| Decitabine | Partial Remission (PR) | Non-Responders | 231 Participants |
| Decitabine | Partial Remission (PR) | Missing | 2 Participants |
| Decitabine | Partial Remission (PR) | Responders | 8 Participants |
Secondary
Stable Disease (SD)
Failure to achieve at least hematologic improvement (HI), but no evidence of clinically significant progression for \> 16 weeks.
Time frame: up to 43 months
Population: Patients \>= 70 years with histologically or pathologically confirmed AML; not treated by systemic therapy; on low-intensity therapy by investigator assessment or the patient has refused standard induction chemotherapy; no prior treatment with HMA or other anti-cancer agents; ECOG status 0-2; adequate hepatic and renal function
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Sapacitabine-decitabine Alternating | Stable Disease (SD) | Responders | 21 Participants |
| Sapacitabine-decitabine Alternating | Stable Disease (SD) | Non-Responders | 217 Participants |
| Sapacitabine-decitabine Alternating | Stable Disease (SD) | Missing | 3 Participants |
| Decitabine | Stable Disease (SD) | Responders | 31 Participants |
| Decitabine | Stable Disease (SD) | Non-Responders | 208 Participants |
| Decitabine | Stable Disease (SD) | Missing | 2 Participants |