Neoplasms

Blood and Lymph Conditions

All Conditions

Rare Diseases

Leukemia

Leukemia, Myeloid

Leukemia, Myeloid, Acute

Neoplasms by Histologic Type

Hematologic Diseases

Myeloid Leukemia

Acute Myeloid Leukemia

Acute Non Lymphoblastic Leukemia

Acute Graft Versus Host Disease

Anti-Infective Agents

Antineoplastic Agents

All Drugs and Chemicals

Cytarabine

AZD1152 1200 mg, iv, 7 day infusion monotherapy

LDAC 20 mg, sc, bd, 10 days (400mg per cycle)

AZD1152

LDAC

Paul Stockman

Hagop Kantarjian

The purpose of this study is to assess the efficacy, safety and tolerability of AZD1152 alone and in combination with low dose cytosine arabinoside (LDAC) in comparison with LDAC alone in AML patients.

Study to Investigate the Efficacy, Safety and Tolerability of AZD1152 Alone and in Combination With Low Dose Cytosine Arabinoside (LDAC)in Acute Myeloid Leukaemia (AML) Patients

A Randomised, Open-label, Multi-centre, 2-stage, Parallel Group Study to Assess the Efficacy, Safety and Tolerability of AZD1152 Alone and in Combination With Low Dose Cytosine Arabinoside (LDAC) in Comparison With LDAC Alone in Patients Aged ≥ 60 With Newly Diagnosed Acute Myeloid Leukaemia (AML)

Percentage of patients achieving either a complete response (CR) or a confirmed complete remission with incomplete recovery of neutrophils or platelets (confirmed CRi). Per Cheson Criteria: Confirmed complete remission (CRi) is defined as a disappearance of blasts in the peripheral blood; a decrease in bone marrow blasts to \<5% total bone marrow nucleated cells demonstrated in bone marrow aspirate; absence of Auer rods; no persistent extramedullary leukaemia. Complete response (CR) is defined as all requirements to meet CRi and in addition: recovery of neutrophils to ≥1.0 x 109/L and platelets to ≥100 x 109/L; transfusion-independence.

DoR was defined for the median of days which showed a confirmed CRi or CR, as the time from first documented evidence of CRi or CR until the first documented sign of disease progression or death. Duration of Response was measured from the Response Start date until evidence of patient relapse or death. Stage I : 45 patients randomized in a 2:1 ratio to AZD1152 or LDAC. Transition phase: enrollment of up to 30 additional patients randomized as per stage I.

Disease-free Survival is defined as the time from randomisation to relapse or death from any cause.

TTCR is measured as time from randomization to either a complete response (CR) or a confirmed complete remission with incomplete recovery of neutrophils or platelets (confirmed CRi)

Overall Survival is defined as the median time from randomisation to death from any cause. Patients who were not known to have died at the time of the analysis were censored at the date they were last known to be alive.

TOI is derived from the sum of the Functional Well Being (FWB), Physical Well Being (PWB) and additional subscales of the FACT-Leu. The TOI subscale consists of 31 items with TOI scores ranging from 0 to 124. The TOI is described as a summary measure of HRQoL. Higher scores indicate better HRQoL. Negative changes from baseline indicate a worsening of HRQoL while positive changes indicate an improvement in HRQoL. A response of "Worsened" was a change from baseline in score of less than or equal to -9.

The total FACT-Leu score consists of 44 items with total scores ranging from 0 to 176. Higher scores indicate better HRQoL. Negative changes from baseline indicate a worsening of HRQoL while positive changes indicate an improvement in HRQoL. A response of "Worsened" was a change from baseline in score of less than or equal to -11.

AstraZeneca

AZD1152 1200mg

LDAC 20mg

Total

Age, Continuous

Sex: Female, Male

Global Clinical Lead

Percentage of Patients With Overall Complete Response for Stage I

Duration of Response (DoR): Stage I and Transition Phase

Disease Free Survival (DFS)

Time To Complete Response (TTCR)

Overall Survival (OS)

Percent of Patients With Worsened Trial Outcome Index (TOI)

Percent of Patients With Worsened Functional Assessment of Cancer Therapy - Leukaemia (FACT-Leu) Score.

Overall Study

Symptoms and General Pathology

Syndrome

Preleukemia

Myelodysplastic Syndromes

Bone Marrow Diseases

Precancerous Conditions

Decitabine

Daunorubicin

Antimetabolites

Antiviral Agents

Immunosuppressive Agents

Immunologic Factors

Anti-Bacterial Agents

Antibiotics, Antitubercular

Enzyme Inhibitors

PF-04449913 in combination with low dose ARA-C (LDAC)

PF-04449913 in combination with Decitabine

PF-04449913 in combination with intensive chemotherapy: PF-04449913 administered continuously for 28 days. Daunorubicin given using 60 mg/m2 for 3-days together with cytarabine 100 mg/m2 on days 1 through 7 followed by cytarabine 1g/m2 on days 1, 3, and 5 during 2-4 cycles of consolidation therapy.

Patients will be randomized 2:1 (low dose ARA-C in combination with PF-04449913: low dose ARA-C alone).

PF-04449913 administered orally and continuously for 28-days.

PF-04449913

Low dose ARA-C (LDAC) administered at 20 mg SQ, BID on Days 1 through 10.

Low dose ARA-C (LDAC)

PF-04449913 administered orally and continuously for 28 days.

Decitabine given at 20 mg/m2 over 1 hour infusion for 5-days

PF-04449913 administered orally and continuously for 28 days

Daunorubicin given using 60 mg/m2 for 3-days

PF-04449913 administered orally and continuously for 28 days (if randomized to receive PF-04449913)

Pfizer CT.gov Call Center

This is a study to evaluate PF-04449913 (an inhibitor of the Hedgehog pathway) in Acute Myeloid Leukemia and high-risk Myelodysplastic Syndrome in combination with standard agents used to treat these diseases.

A Study To Evaluate PF-04449913 With Chemotherapy In Patients With Acute Myeloid Leukemia or Myelodysplastic Syndrome

A PHASE 1B/2 STUDY TO EVALUATE THE SAFETY AND EFFICACY OF PF-04449913, AN ORAL HEDGEHOG INHIBITOR, IN COMBINATION WITH INTENSIVE CHEMOTHERAPY, LOW DOSE ARA-C OR DECITABINE IN PATIENTS WITH ACUTE MYELOID LEUKEMIA OR HIGH-RISK MYELODYSPLASTIC SYNDROME

Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.

A DLT was any of the following adverse events (AEs) in Cycle 1 and considered by the investigator possibly related to glasdegib in combination with chemotherapy: (1) Grade \>= 3 non-hematologic toxicity, excluding Grade \>= 3 infection, fever (including febrile neutropenia), infusion related AEs, electrolyte abnormalities and ALT/AST elevation that returned to Grade \<= 1 or baseline within 7 days; (2) prolonged myelosuppression that lasted longer than 42 days from the point of detection, defined as absolute neutrophil count (ANC) \< 500/microliter(mcL) or platelet count \< 10 \*10\^9/L with a normal bone marrow (\<5% blasts and no evidence of disease or dysplasia); (3) inability to deliver at least 80% of the planned study doses for all agents in a combination due to non-hematologic toxicities; (4) Delay of \>28 days in receiving the next scheduled cycle due to persisting non-hematologic toxicities. Arm A: Glasdegib+LDAC; Arm B: Glasdegib+Decitabine; Arm C: Glasdegib+Cytarabine/Daunorubicin.

For AML participants:CR were those with repeat bone marrow showing \<5% myeloblasts,spicules present and no Auer rods, peripheral blood showing neutrophils\>=1000/mcL and platelets\>=100,000/mcL, transfusion independent and no extramedullary disease. For MDS participants:CR were those with repeat bone marrow showing \<=5% myeloblasts, peripheral blood showing neutrophils\>=1000/mcL, platelets\>=100,000/mcL, 0% blast and hemoglobin (Hgb)\>= 11 g/dL, normal maturation of all cell lines.

OS was defined as duration from the date of randomization to the date of death from any cause. Kaplan-Meier (KM) method was used to estimate median OS. In this method, every participant had a follow-up time which was associated with an indicator, 1=event (death in our case), and 0 =censored. If the participants were not known to have died, time to date of last known to be alive was used as to calculate the follow-up time and indicator was 0 for these participants. KM method estimates the median OS based on the K-M curve. The K-M curve only drops when we had an event and censor data are the ticks in the graph. To estimate median OS, the K-M curve usually will be smoothed first and a line will be drawn at 50%. The median OS is the point when K-M curve and the horizontal hit. Survival status was collected every month for the first 2 months after discontinuation of study treatment and thereafter every 2 months until death or 4 years from time of randomization for each participant.

OS was defined as duration from the date of randomization to the date of death from any cause. Kaplan-Meier (KM) method was used to estimate median OS. In this method, every participant had a follow-up time which was associated with an indicator, 1=event (death in our case), and 0 =censored. If the participants were not known to have died, time to date of last known to be alive was used as to calculate the follow-up time and indicator was 0 for these participants. KM method estimates the median OS based on the K-M curve. The K-M curve only drops when we had an event and censor data are the ticks in the graph. To estimate median OS, the K-M curve usually will be smoothed first and a line will be drawn at 50%. The median OS is the point when K-M curve and the horizontal hit. Survival status was collected every month for the first 2 months after discontinuation of study treatment and thereafter every 2 months until death or 4 years from each participant's first dose.

For AML participants:CR were those with repeat bone marrow showing \<5% myeloblasts,spicules present and no Auer rods, peripheral blood showing neutrophils\>=1000/mcL and platelets\>=100,000/mcL, transfusion independent and no extramedullary disease. For MDS participants:CR were those with repeat bone marrow showing \<=5% myeloblasts, peripheral blood showing neutrophils\>=1000/mcL, platelets\>=100,000/mcL, 0% blast and hemoglobin (Hgb)\>= 11 g/dL, normal maturation of all cell lines.For AML and MDS participants, complete response with incomplete blood count recovery(CRi)were those with repeat bone marrow showing \<5% myeloblasts with either platelets or neutrophils not recovered (platelets \<100,000/mcL or neutrophils \<1000/mcL).

AML participants,disease specific efficacy measures included:CRi;Morphologic Leukemia Free State(MLFS)(bone marrow\<5%myeloblasts with spicules and no blasts with auer rods,neutrophils\<1000/mcL and platelets\<100,000/mcL);partial remission(PR)(bone marrow myeloblasts decrease to 5-25\&\>=50%decrease from start, neutrophils\>=1000/mcL, platelets\>=100,000/mcL);PR with incomplete blood count recovery(PRi)(bone marrow myeloblasts decrease to 5-25\&\>=50%decrease from start,neutrophils\<1000/mcL or platelets\<100,000/mcL);minor response(MR)(bone marrow myeloblasts decrease to\>=25% from start);stable disease(SD)(bone marrow myeloblasts stable+/-25% from screening value);cytogenetic complete response(CRc)(bone marrow\<5%myeloblasts, neutrophils\>1000/mcL, platelets\>100,000/mcL and normal cytogenetics),molecular complete response(CRm)(bone marrow\<5%myeloblasts, neutrophils\>1000/mcL, platelets\>100,000/mcL and molecular-negative).

For all MDS participants, disease specific efficacy measures included: CRi (bone marrow showing \<5% myeloblasts with platelets \<100,000/mcL or neutrophils \<1000/mcL, including confirmed and unconfirmed responses); PR (repeat bone marrow myeloblasts showing decreased by \>= 50% decrease but still \>5%, peripheral blood showing neutrophils \>= 1,000/mcL, platelets \>= 100,000/mcL and Hgb\>=11g/dL; including confirmed and unconfirmed responses); SD (including confirmed and unconfirmed responses, failure to achieve PR and no evidence of progression for \>8 weeks); marrow complete response (mCR) (bone marrow showing \<=5% myeloblasts and decreased by \>= 50%), partial cytogenetic response (\>=50% reduction of chromosomal abnormality) and complete cytogenetic response (CRc) (disappearance of chromosomal abnormality with no appearance of now ones).

Ara-U is the major metabolite of cytarabine. LDAC (low dose cytarabine) is rapidly degraded to the stable metabolite Ara-U, Cmax levels of both LDAC and Ara-U were reported.

Ara-U is the major metabolite of cytarabine. LDAC (low dose cytarabine) is rapidly degraded to the stable metabolite Ara-U, Tmax levels of both LDAC and Ara-U were reported.

Ara-U is the major metabolite of cytarabine. LDAC (low dose cytarabine) is rapidly degraded to the stable metabolite Ara-U. Area under the plasma concentration-time profile from time 0 to the time of the last quantifiable concentration (AUClast) levels of both LDAC and Ara-U were reported.

Ara-U is the major metabolite of cytarabine. LDAC (low dose cytarabine) is rapidly degraded to the stable metabolite Ara-U, levels of both cytarabine and Ara-U were reported.

Daunorubicinol is the major metabolite of daunorubicin, which has anti-neoplastic activity. Cmax values of daunorubicin and daunorubicinol are reported.

Daunorubicinol is the major metabolite of daunorubicin, which has anti-neoplastic activity. Tmax values of daunorubicin and daunorubicinol are reported.

Daunorubicinol is the major metabolite of daunorubicin, which has anti-neoplastic activity. AUCtau values of daunorubicin and daunorubicinol are reported.

Peripheral blood and bone marrow aspirate were collected for baseline mutational analyses. Genetic abnormalities frequently associated with AML were analyzed. These genetic abnormalities included known mutations in the genes NPM1, CEBPA, FLT3, RUNX1, IDH1, IDH2, KIT, K Ras, N Ras and WT1. Additional genes with mutations known to be associated with AML and MDS such as TET2 and DNMT3A were also evaluated.

Serum levels were determined for 38 circulating proteins. Values showing statistically significant, ≥2-fold difference compared with baseline are reported here.

Serum levels were determined for 38 circulating proteins. Values showing statistically significant, ≥2-fold difference compared with baseline are reported here. Statistically significant, \>=2-fold baseline difference was only seen for MMP-3 (Matrix metalloproteinase-3) at Induction Cycle 1/Day 3.

Responders were AML participants who achieved CR, CRi, MLFS, PR or PRi based on investigator-reported best overall response and MDS participants who achieved CR, mCR, PR or SD based on investigator-reported best overall response. A total of 38 proteins were analyzed. The data of analytes for which the serum level showed statistically significant correlation with clinical response in Arm C are reported. Baseline levels statistically associated with best overall response was only seen in SDF-1 (stromal cell-derived factor 1) in glasdegib+cytarabine/daunorubicin arm.

Responders were AML participants who achieved CR, CRi, MLFS, PR or PRi based on investigator-reported best overall response and MDS participants who achieved CR, mCR, PR or SD based on investigator-reported best overall response. A total of 38 proteins were analyzed. The data of analytes for which the serum level showed statistically significant correlation with clinical response are reported. Post-baseline levels statistically significant associated with best overall response was only seen for MMP-3 (Matrix metalloproteinase-3) at Induction Cycle 1/Lead-in.

Responders were AML participants who achieved CR, CRi, MLFS, PR or PRi based on investigator-reported best overall response and MDS participants who achieved CR, mCR, PR or SD based on investigator-reported best overall response. A total of 38 proteins were analyzed. The data of analytes for which the serum level showed statistically significant correlation with clinical response are reported. Post-baseline levels statistically significant associated with best overall response was only seen for SDF-1 (Stromal cell-derived factor 1) at Induction Cycle 1/Day 3.

Serum levels were determined for 38 circulating proteins. Selected values showing statistically significant difference compared with baseline are reported here.

Responders were AML participants who achieved CR, CRi, MLFS, PR or PRi based on investigator-reported best overall response and MDS participants who achieved CR, mCR, PR or SD based on investigator-reported best overall response. A total of 38 proteins were analyzed. Selected data of analyte for which the serum level showed statistically significant correlation with clinical response are reported.

Responders were AML participants who achieved CR, CRi, MLFS, PR or PRi based on investigator-reported best overall response and MDS participants who achieved CR, mCR, PR or SD based on investigator-reported best overall response. A total of 38 proteins were analyzed. Selected data of analytes for which the serum level showed statistically significant correlation with clinical response are reported.

Serum levels were determined for 38 circulating proteins. Selected value showing statistically significant difference compared with baseline is reported here.

Serum levels were determined for 38 circulating proteins. Selected values showing statistically significant differences compared with baseline are reported here. ITAC (Interferon-inducible T-cell α chemoattractant) level in LDAC alone arm at Cycle 1/Day 10 exhibited non-significant change from baseline but similar trends as in Glasdegib 100 mg+LDAC arm.

Responders were AML participants who achieved CR, CRi, MLFS, PR or PRi based on investigator-reported best overall response and MDS participants who achieved CR, mCR, PR or SD based on investigator-reported best overall response. A total of 38 proteins were analyzed. The data of analytes for which the serum level showed statistically significant correlation with clinical response are reported.

Whole blood mRNA analyses were performed on 21 mRNA candidates. Values showing statistically significant, ≥2-fold differences compared with baseline are reported here. CDKN1A: cyclin-dependent kinase inhibitor 1A; SMO: mRNA encoding the glasdegib target Smoothened; PTCH2: Patched 2; MYCN: Neuroblastoma Myc oncogene.

Whole blood mRNA analyses were performed on 21 mRNA candidates. Selected values showing statistically significant differences compared with baseline are reported here. CCND2:G1/S-Specific Cyclin D2; MSI2: Musashi RNA Binding Protein 2; PTCH2: Patched 2.

Whole blood mRNA analyses were performed on 21 mRNA candidates. Only the analytes showing statistically significant change from baseline are reported here.

Responders were AML participants who achieved CR, CRi, MLFS, PR or PRi based on investigator-reported best overall response and MDS participants who achieved CR, mCR, PR or SD based on investigator-reported best overall response. Whole blood mRNA analyses were performed on 21 mRNA candidates. Baseline mRNA level showing statistically significant correlation with clinical response are reported. Baseline mRNA levels statistically significant associated with best overall response was only seen for CCND2 (G1/S-Specific Cyclin D2).

Responders were AML participants who achieved CR, CRi, MLFS, PR or PRi based on investigator-reported best overall response and MDS participants who achieved CR, mCR, PR or SD based on investigator-reported best overall response. Whole blood mRNA analyses were performed on 21 mRNA candidates. Baseline mRNA level showing statistically significant correlation with clinical response are reported. FOXM1: Forkhead box M1; PTCH1: Patched 1.

Responders were AML participants who achieved CR, CRi, MLFS, PR or PRi based on investigator-reported best overall response and MDS participants who achieved CR, mCR, PR or SD based on investigator-reported best overall response. Whole blood mRNA analyses were performed on 21 mRNA candidates. Ratios of mRNA level to baseline showing statistically significant correlation with clinical response are reported.

Responders were AML participants who achieved CR, CRi, MLFS, PR or PRi based on investigator-reported best overall response and MDS participants who achieved CR, mCR, PR or SD based on investigator-reported best overall response. Whole blood mRNA analyses were performed on 21 mRNA candidates. Ratios of mRNA level to baseline showing statistically significant correlation with clinical response are reported. Ratios of mRNA levels to baseline statistically significant associated with best overall response was only seen for MYCN (Neuroblastoma Myc oncogene) at Cycle 1/Day 1.

Maximum absolute values and increases from baseline were summarized for QTcF interval (time from the beginning of Q wave to the end of T wave corresponding to electrical systole corrected for heart rate using Fridericia's formula). Number of participants with QTcF meeting the following criteria is presented: QTcF interval:\<450 msec; QTcF interval: 450 to \<480 msec; QTcF interval: 480 to \<500 msec; QTcF interval \>=500 msec; QTcF interval increase from baseline: \<30 msec; QTcF interval increase from baseline: 30 to \<60 msec; QTcF interval increase from baseline \>=60 msec. Arms in the time frame description are defined as: Arm A, Glasdegib +LDAC; Arm B, Glasdegib + Decitabine; Arm C, Glasdegib + Cytarabine/Daunorubicin. End of treatment in the time frame were defined as: maximum of 12 cycles from start of therapy or until disease progression or relapse, participant refusal or unacceptable toxicity occurred, whichever came first.

Maximum absolute values and increases from baseline were summarized for QTcF interval (time from the beginning of Q wave to the end of T wave corresponding to electrical systole corrected for heart rate using Fridericia's formula). Number of participants with QTcF meeting the following criteria is presented:QTcF interval:\<450 msec; QTcF interval: 450 to \<480 msec; QTcF interval: 480 to \<500 msec; QTcF interval \>=500 msec; QTcF interval increase from baseline: \<30 msec; QTcF interval increase from baseline: 30 to \<60 msec; QTcF interval increase from baseline \>=60 msec. End of treatment in the time frame were defined as: maximum of 12 cycles from start of therapy or until disease progression or relapse, participant refusal or unacceptable toxicity occurred, whichever came first.

An adverse event (AE) was any untoward medical occurrence in a clinical investigation participant administered a product or medical device; the event did not necessarily had a causal relationship with the treatment or usage. Treatment Emergent AEs were those with initial onset or increasing in severity after the first dose of study medication and occurred within 28 days post last dose. AEs were graded by the investigator according to the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 : Grade 1: mild AE; Grade 2: moderate AE; Grade 3: severe AE; Grade 4: life-threatening consequences, urgent intervention indicated; Grade 5: death related to AE.

An adverse event (AE) was any untoward medical occurrence in a clinical investigation participant administered a product or medical device; the event did not necessarily had a causal relationship with the treatment or usage. Treatment Emergent AEs were those with initial onset or increasing in severity after the first dose of study medication and occurred within 28 days post last dose. Treatment-related AEs were AEs related to glasdegib and/or backbone chemotherapy. AEs were graded by the investigator according to the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 : Grade 1: mild AE; Grade 2: moderate AE; Grade 3: severe AE; Grade 4: life-threatening consequences, urgent intervention indicated; Grade 5: death related to AE.

An adverse event (AE) was any untoward medical occurrence in a clinical investigation participant administered a product or medical device; the event did not necessarily had a causal relationship with the treatment or usage. Treatment Emergent AEs were those with initial onset or increasing in severity after the first dose of study medication and occurred within 28 days post last dose. An serious adverse event (SAE) was any untoward medical occurrence at any dose that: resulted in death; was life threatening (immediate risk of death); required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity (substantial disruption of the ability to conduct normal life functions); resulted in congenital anomaly/birth defect.

Pfizer

The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. All-cause mortality reflects the number of deaths from start of treatment to and including 28 days after last dose. Safety analysis set was evaluated.

Participants received oral doses of glasdegib (PF-04449913) tablets 100 milligram (mg) starting on Day 3 of Cycle 1 for pharmacokinetic (PK) assessment purposes and thereafter once daily (QD) and continuously for 28-day cycles (starting on Day 1 for all other cycles). Low dose Ara-C (LDAC) was given at a dose of 20 mg subcutaneously twice daily (BID) on Days 1-10 of the 28-day cycles.

Phase 1B: Glasdegib 100 mg + LDAC

Participants received oral doses of glasdegib tablets 200 mg starting on Day 3 of Cycle 1 for PK assessment purposes and thereafter QD and continuously for 28-day cycles (starting on Day 1 for all other cycles). LDAC was given at a dose of 20 mg subcutaneously BID on Days 1-10 of the 28-day cycles. In March 2013, all active participants receiving glasdegib 200 mg were required to reduce dose to 100 mg. Participants who had glasdegib dose reduction were reported as the starting glasdegib dose level received. Two (2) participants in this cohort had dose reduction to 100 mg starting from Cycle 2/Day 1 and Cycle 2/Day 16, respectively.

Phase 1B: Glasdegib 200 mg + LDAC

Participants received oral doses of glasdegib tablets 100 mg starting on Day 2 of Cycle 1 for PK assessment purposes and thereafter QD and continuously for 28-day cycles (starting on Day 1 for all other cycles). Decitabine was given at a dose of 20 mg/m\^2 as an intravenous (IV) infusion over 1 hour on Days 1-5 of the 28-day cycles.

Phase 1B: Glasdegib 100 mg + Decitabine

Participants received oral doses of glasdegib tablets 200 mg starting on Day 2 of Cycle 1 for PK assessment purposes and thereafter QD and continuously for 28-day cycles (starting on Day 1 for all other cycles). Decitabine was given at a dose of 20 mg/m\^2 as an IV infusion over 1 hour on Days 1-5 of the 28-day cycles.In March 2013, all active participants receiving glasdegib 200 mg were required to reduce dose to 100 mg. Participants who had glasdegib dose reduction were reported as the starting glasdegib dose level received. Two (2) participants in this cohort had dose reduction to 100 mg starting from Cycle 1/Day 24 and Cycle 5/Day 1, respectively.

Phase 1B: Glasdegib 200 mg + Decitabine

Participants received 1-2 cycles of induction (glasdegib and daunorubicin/cytarabine), followed by 2-4 cycles of consolidation (glasdegib and high dose cytarabine) and a maximum of 6 cycles of maintenance (glasdegib alone). Daunorubicin was given on Days 1-3 QD at a dose of 60 mg/m\^2/day by IV together with cytarabine on Days 1-7 at a dose of 100 mg/m\^2/day by continuous IV infusion for each cycle of induction. Cytarabine was given on Days 1, 3, and 5 at a dose of 1 g/m\^2 administered as a 3-hour IV infusion every 12 hours (2 g/m\^2/day) for each cycle of consolidation. Glasdegib tablets 100 mg QD was started on induction Cycle 1/Day -3 and administered continuously QD thereafter for the duration of the study. A cycle was defined as 28 days.

Phase 1B: Glasdegib 100 mg + Cytarabine/Daunorubicin

Participants received 1-2 cycles of induction (glasdegib and daunorubicin/cytarabine), followed by 2-4 cycles of consolidation (glasdegib and high dose cytarabine) and a maximum of 6 cycles of maintenance (glasdegib alone). Daunorubicin was given on Days 1-3 QD at a dose of 60 mg/m\^2/day by IV together with cytarabine on Days 1-7 at a dose of 100 mg/m\^2/day by continuous IV infusion for each cycle of induction. Cytarabine was given on Days 1, 3, and 5 at a dose of 1 g/m\^2 administered as a 3-hour IV infusion every 12 hours (2 g/m\^2/day) for each cycle of consolidation. Glasdegib tablets 200 mg QD was started on induction Cycle 1/Day -3 and administered continuously QD thereafter for the duration of the study. A cycle was defined as 28 days.In March 2013, all active participants receiving glasdegib 200 mg were required to reduce dose to 100 mg.One (1) participant in this cohort had dose reduction to 100 mg starting from Consolidation Cycle 1/Day 21.

Phase 1B: Glasdegib 200 mg + Cytarabine/Daunorubicin

Phase 2 Fit: Glasdegib 100 mg + Cytarabine/Daunorubicin

Participants received oral doses of glasdegib tablets 100 mg QD in 28-day cycles on a continuous basis, starting on Day 1 of Cycle 1. LDAC was given at a dose of 20 mg subcutaneously BID on Days 1-10 of the 28-day cycles.

Phase 2 Unfit: Glasdegib 100 mg + LDAC

Participants received LDAC subcutaneously at a dose of 20 mg BID on Days 1-10 of the 28-day cycles.

Phase 2 Unfit: LDAC Alone

Included all participants who received oral glasdegib in combination with LDAC in phase 1B portion.

Phase 1B: Glasdegib + LDAC

Included all participants who received oral glasdegib in combination with decitabine in phase 1B portion.

Phase 1B: Glasdegib + Decitabine

Included all participants who received oral glasdegib in combination with cytarabine/daunorubicin in phase 1B portion.

Phase 1B: Glasdegib + Cytarabine/Daunorubicin

Pfizer ClinicalTrials.gov Call Center

Participants received oral doses of glasdegib (PF-04449913) tablets 100 milligram (mg) starting on Day 3 of Cycle 1 for pharmacokinetic (PK) assessment purposes and thereafter once daily (QD) and continuously for 28-day cycles (starting on Day 1 for all other cycles). LDAC was given at a dose of 20 mg subcutaneously twice daily (BID) on Days 1-10 of the 28-day cycles.

Per protocol analysis set: all enrolled participants in the dose escalation component who received at least 1 dose of glasdegib and of the co-administered chemotherapeutics and who did not have major treatment deviations during the DLT monitoring period.

Number of Participants With Dose-limiting Toxicities (DLTs) at Phase 1B

Total participants

Participants >= 55 years old

Participants < 55 years old

Full analysis set: all enrolled participants of Phase 2 Fit arm who received at least 1 dose of study medication. Number of participants analyzed signifies number of participants who were evaluable for this outcome measure. Number analyzed refers to number of participants evaluable for specified rows of categories.

Percentage of Participants With Complete Response (CR) at Phase 2 Fit

Participants received oral doses of glasdegib tablets 100 mg QD in 28-day cycles on a continuous basis, starting on Day 1 of Cycle 1. LDAC was given at a dose of 20 mg subcutaneously BID on Days 1-10 of the 28 day cycles.

Participants received LDAC subcutaneously at a dose of 20 mg BID on Days 1-10 of the 28 day cycles.

Full analysis set: all randomized participants of Phase 2 Unfit arm.

Overall Survival (OS) at Phase 2 Unfit

Full analysis set: all enrolled participants of Phase 1B portion who received at least 1 dose of study medication.

Overall Survival (OS) at Phase 1B

Overall Survival (OS) at Phase 2 Fit

Percentage of Participants With CR / Complete Response With Incomplete Blood Count Recovery (CRi) at Phase 1B

Percentage of Participants With Complete Response (CR) at Phase 2 Unfit

MLFS

AML participants in the Full analysis set: all enrolled participants of Phase 2 Fit arm who received at least 1 dose of study medication, and all randomized participants of Phase 2 Unfit arm.

Percentage of Participants With Disease-specific Efficacy for Acute Myeloid Leukemia (AML) at Phase 2 Fit and Unfit

Unconfirmed SD

Unconfirmed CRi

mCR (CRi not included)

MDS participants in the Full analysis set: all enrolled participants of Phase 2 Fit arm who received at least 1 dose of study medication, and all randomized participants of Phase 2 Unfit arm.

Percentage of Participants With Disease-specific Efficacy for Myelodysplastic Syndrome (MDS) at Phase 2 Fit and Unfit

Cycle 1/Day 10

Cycle 1/Day 21

Dose compliant group:Participants who had at least 4 days of uninterrupted dosing for a multiple dose PK assessment were considered to be at steady state,part of the "dose compliant" group.

Maximum Observed Plasma Concentration (Cmax) of Glasdegib in Participants Receiving Glasdegib and LDAC at Phase 1B on Cycle 1/Day 10 and Cycle 1/Day 21

Time to Cmax (Tmax) of Glasdegib in Participants Receiving Glasdegib and LDAC at Phase 1B on Cycle 1/Day 10 and Cycle 1/Day 21

Area Under the Plasma Concentration-time Profile From Time 0 to Dosing Interval (AUCtau) of Glasdegib in Participants Receiving Glasdegib and LDAC at Phase 1B on Cycle 1/Day 10 and Cycle 1/Day 21

Cycle 2/Day 1

Cmax of Glasdegib in Participants Receiving Glasdegib and Decitabine at Phase 1B on Cycle 1/Day 10 and Cycle 2/Day 1

Tmax of Glasdegib in Participants Receiving Glasdegib and Decitabine at Phase 1B on Cycle 1/Day 10 and Cycle 2/Day 1

AUCtau of Glasdegib in Participants Receiving Glasdegib and Decitabine at Phase 1B on Cycle 1/Day 10 and Cycle 2/Day 1

Induction Cycle 1/Day 3

Induction Cycle 1/Day 10

Cmax of Glasdegib in Participants Receiving Glasdegib and Cytarabine/Daunorubicin at Phase 1B on Induction Cycle 1/Day 3 and Day 10

Tmax of Glasdegib in Participants Receiving Glasdegib and Cytarabine/Daunorubicin at Phase 1B on Induction Cycle 1/Day 3 and Day 10

AUCtau of Glasdegib in Participants Receiving Glasdegib and Cytarabine/Daunorubicin at Phase 1B on Induction Cycle 1/Day 3 and Day 10

LDAC Cycle 1/Day 2

LDAC Cycle 1/Day 10

Ara-U Cycle 1/Day 2

Ara-U Cycle 1/Day 10

PK concentration population: all treated participants who had at least 1 concentration of any of the study drugs.

Cmax of LDAC and Ara-U in Participants Receiving Glasdegib and LDAC at Phase 1B on Cycle 1/Day 2 and Cycle 1/Day 10

PK parameter analysis set: all treated participants who had at least 1 of the PK parameters of interest for any of the study drugs.

Tmax of LDAC and Ara-U in Participants Receiving Glasdegib and LDAC at Phase 1B on Cycle 1/Day 2 and Cycle 1/Day 10

Area Under the Plasma Concentration-time Profile From Time 0 to Infinity (AUCinf) of LDAC in Participants Receiving Glasdegib and LDAC at Phase 1B on Cycle 1/Day 2 and Cycle 1/Day 10

Area Under the Plasma Concentration-time Profile From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) of LDAC and Ara-U in Participants Receiving Glasdegib and LDAC at Phase 1B on Cycle 1/Day 2 and Cycle 1/Day 10

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Study to Investigate the Efficacy, Safety and Tolerability of AZD1152 Alone and in Combination With Low Dose Cytosine Arabinoside (LDAC)in Acute Myeloid Leukaemia (AML) Patients	NCT00952588	Acute Myeloid L...	AZD1152 LDAC	60 Years -	AstraZeneca
A Study To Evaluate PF-04449913 With Chemotherapy In Patients With Acute Myeloid Leukemia or Myelodysplastic Syndrome	NCT01546038	Acute Myeloid L...	PF-04449913 Low dose ARA-C ... PF-04449913 Decitabine PF-04449913 Daunorubicin Cytarabine PF-04449913 Daunorubicin Cytarabine PF-04449913 Low dose ARA-C ...	18 Years -	Pfizer
A Study To Evaluate PF-04449913 With Chemotherapy In Patients With Acute Myeloid Leukemia or Myelodysplastic Syndrome	NCT01546038	Acute Myeloid L...	PF-04449913 Low dose ARA-C ... PF-04449913 Decitabine PF-04449913 Daunorubicin Cytarabine PF-04449913 Daunorubicin Cytarabine PF-04449913 Low dose ARA-C ...	18 Years -	Pfizer
A Study Of PF-04449913 In Japanese Patients With Select Hematologic Malignancies	NCT02038777	Acute Myeloid L...	PF-04449913 PF-04449913 Low dose ARA-C ... PF-04449913 Daunorubicin Cytarabine PF-04449913 Azacitidine PF-04449913 LDAC	20 Years -	Pfizer

Spots Global Cancer Trial Database for ldac

Every month we try and update this database with for ldac cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for ldac

Every month we try and update this database with for ldac cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for ldac cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.