TriangleNCT01546038 · CITED IN SOURCE DOCUMENTS
A Study To Evaluate PF-04449913 With Chemotherapy In Patients With Acute Myeloid Leukemia or Myelodysplastic Syndrome
An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.
- Phase
- PHASE2
- Status at capture
- COMPLETED
- Registry last update
- 2020-03-03
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.
Open the original ClinicalTrials.gov record → · Download preserved record
What did the study report?
Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.
Participant flow
Baseline characteristics
Number of Participants With Dose-limiting Toxicities (DLTs) at Phase 1B
Percentage of Participants With Complete Response (CR) at Phase 2 Fit
Overall Survival (OS) at Phase 2 Unfit
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
Percentage of Participants With Disease-specific Efficacy for Acute Myeloid Leukemia (AML) at Phase 2 Fit and Unfit
Percentage of Participants With Disease-specific Efficacy for Myelodysplastic Syndrome (MDS) at Phase 2 Fit and Unfit
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
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
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
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
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
Cmax of Decitabine in Participants Receiving Glasdegib and Decitabine at Phase 1B on Cycle 1/Day 1 and Cycle 1/Day 2
Tmax of Decitabine in Participants Receiving Glasdegib and Decitabine at Phase 1B on Cycle 1/Day 1 and Cycle 1/Day 2
AUCinf of Decitabine in Participants Receiving Glasdegib and Decitabine at Phase 1B on Cycle 1/Day 1 and Cycle 1/Day 2
AUCtau of Cytarabine and Ara-U in Participants Receiving Glasdegib and Cytarabine/Daunorubicin at Phase 1B on Induction Cycle 1/Day 3
Cmax of Daunorubicin and Daunorubicinol in Participants Receiving Glasdegib and Cytarabine/Daunorubicin at Phase 1B on Induction Cycle 1/Day 3
Tmax of Daunorubicin and Daunorubicinol in Participants Receiving Glasdegib and Cytarabine/Daunorubicin at Phase 1B on Induction Cycle 1/Day 3
AUCtau of Daunorubicin and Daunorubicinol in Participants Receiving Glasdegib and Cytarabine/Daunorubicin at Phase 1B on Induction Cycle 1/Day 3
Pre-dose Plasma Concentration (Ctrough) of Glasdegib in Phase 2 Fit on Induction Cycle 1/Day 10
Cmax of Glasdegib in Participants Receiving Glasdegib and LDAC at Phase 2 Unfit on Cycle 1/Day 10
Tmax of Glasdegib in Participants Receiving Glasdegib and LDAC at Phase 2 Unfit on Cycle 1/Day 10
AUCtau of Glasdegib in Participants Receiving Glasdegib and LDAC at Phase 2 Unfit on Cycle 1/Day 10
Number of Participants With Disease-related Gene Mutations at Phase 1B
Serum Levels of Circulating Protein Analytes at Phase 1B - Baseline
Serum Levels of Circulating Protein Analytes at Phase 1B - Induction Cycle 1/Day 3
Serum Levels of Circulating Protein Analytes at Phase 1B - Induction Cycle 1/Day 10
Baseline Levels of Serum Circulating Protein Analytes Associated With Best Overall Response at Phase 1B
Post-baseline Levels of Serum Circulating Protein Analytes Associated With Best Overall Response at Phase 1B - Induction Cycle 1/Lead-In
Post-baseline Levels of Serum Circulating Protein Analytes Associated With Best Overall Response at Phase 1B - Induction Cycle 1/Day 3
Number of Participants With Disease-related Gene Mutations at Phase 2 Fit and Unfit
Serum Levels of Circulating Protein Analytes at Phase 2 Fit - Induction Cycle 1/Day 3
Serum Levels of Circulating Protein Analytes at Phase 2 Fit - Induction Cycle 1/Day 10
Serum Levels of Circulating Protein Analytes at Phase 2 Fit - Consolidation Cycle 1/Day 1
Serum Levels of Circulating Protein Analytes at Phase 2 Fit - Consolidation Cycle 1/Day 10
Serum Levels of Circulating Protein Analytes at Phase 2 Fit - End of Treatment
Baseline Levels of Serum Circulating Protein Analytes Associated With Best Overall Response at Phase 2 Fit
Post-baseline Levels of Serum Circulating Protein Analytes Associated With Best Overall Response at Phase 2 Fit - Induction Cycle 1/Day 3
Post-baseline Levels of Serum Circulating Protein Analytes Associated With Best Overall Response at Phase 2 Fit - Induction Cycle 1/Day 10
Post-baseline Levels of Serum Circulating Protein Analytes Associated With Best Overall Response at Phase 2 Fit - End of Treatment
Serum Levels of Circulating Protein Analytes at Phase 2 Unfit - Cycle 1/Day 1
Serum Levels of Circulating Protein Analytes at Phase 2 Unfit - Cycle 1/Day 10
Baseline Levels of Serum Circulating Protein Analytes Associated With Best Overall Response at Phase 2 Unfit
Post-baseline Levels of Serum Circulating Protein Analytes Associated With Best Overall Response at Phase 2 Unfit - Cycle 1/Day 1
Post-baseline Levels of Serum Circulating Protein Analytes Associated With Best Overall Response at Phase 2 Unfit - End of Treatment
Ratios of mRNA Levels to Baseline at Phase 2 Fit - Induction Cycle 1/Day 3
Ratios of mRNA Levels to Baseline at Phase 2 Fit - End of Treatment
Ratios of mRNA Levels to Baseline at Phase 2 Unfit - End of Treatment
Baseline mRNA Levels Associated With Best Overall Response at Phase 2 Fit
Baseline mRNA Levels Associated With Best Overall Response at Phase 2 Unfit
Ratios of mRNA Levels to Baseline Associated With Best Overall Response at Phase 2 Fit
Ratios of mRNA Levels Associated With Best Overall Response at Phase 2 Unfit
Number of Participants With Corrected QT Interval Using Fridericia's Formula (QTcF) Values Meeting Predefined Criteria at Phase 1B
Number of Participants With Corrected QT Interval Using Fridericia's Formula (QTcF) Values Meeting Predefined Criteria at Phase 2 Fit and Unfit
Number of Participants With Treatment-emergent Adverse Events (AEs) at Phase 1B (All Causality)
Number of Participants With Treatment-emergent AEs at Phase 1B (Treatment-related)
Number of Participants With Treatment-emergent AEs Categorized by Seriousness at Phase 1B
Number of Participants With Treatment-emergent AEs at Phase 2 Fit and Unfit (All Causality)
Number of Participants With Treatment-emergent AEs at Phase 2 Fit and Unfit (Treatment-related)
Number of Participants With Treatment-emergent AEs Categorized by Seriousness at Phase 2 Fit and Unfit
Adverse events
Limitations, agreements, and source contact
Who could take part
- eligibility Criteria
- Inclusion Criteria: * Patients with AML or RAEB 2 High Risk MDS who are newly diagnosed according to the WHO 2008 Classification and previously untreated. * Patients with AML (arising from an antecedent hematologic disease \[AHD\]) or MDS who may have had one prior regimen with commercially available agents for the treatment of their prior hematologic disease. The patients may not have had a prior therapy for their AML. * AML patients include de novo AML, AML evolving from MDS or other AHD and AML after previous cytotoxic therapy or radiation (secondary AML) * For a diagnosis of AML, a bone marrow blast count of 20% or more is required. * For a diagnosis of high-risk Myelodysplastic Syndrome RAEB 2 the patient must have 10-19% bone marrow blasts * Adequate Organ Function * ECOG Performance Status 0, 1, or 2 Exclusion Criteria: * AML M3 Acute Promyelocytic Leukemia (APL) or patients with a t(9:22) cytogenetic translocation. * Patients with known active uncontrolled central nervous system (CNS) leukemia.
- healthy Volunteers
- false
- minimum Age
- 18 Years
- sex
- ALL
- std Ages
- ADULT
- OLDER_ADULT
Treatment arms and interventions
- arm Groups
- description
- PF-04449913 in combination with low dose ARA-C (LDAC)
- intervention Names
- Drug: PF-04449913
- Drug: Low dose ARA-C (LDAC)
- label
- Arm A (Phase 1B)
- type
- EXPERIMENTAL
- description
- PF-04449913 in combination with Decitabine
- intervention Names
- Drug: PF-04449913
- Drug: Decitabine
- label
- Arm B (Phase 1B)
- type
- EXPERIMENTAL
- description
- 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.
- intervention Names
- Drug: PF-04449913
- Drug: Daunorubicin
- Drug: Cytarabine
- label
- Arm C (Phase 1B)
- type
- EXPERIMENTAL
- description
- 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.
- intervention Names
- Drug: PF-04449913
- Drug: Daunorubicin
- Drug: Cytarabine
- label
- P2 Fit (Phase 2 Single Arm)
- type
- EXPERIMENTAL
- description
- Patients will be randomized 2:1 (low dose ARA-C in combination with PF-04449913: low dose ARA-C alone).
- intervention Names
- Drug: PF-04449913
- Drug: Low dose ARA-C (LDAC)
- label
- P2 Unfit (Phase 2 Randomized)
- type
- OTHER
- interventions
- arm Group Labels
- Arm A (Phase 1B)
- description
- PF-04449913 administered orally and continuously for 28-days.
- name
- PF-04449913
- type
- DRUG
- arm Group Labels
- Arm A (Phase 1B)
- description
- Low dose ARA-C (LDAC) administered at 20 mg SQ, BID on Days 1 through 10.
- name
- Low dose ARA-C (LDAC)
- type
- DRUG
- arm Group Labels
- Arm B (Phase 1B)
- description
- PF-04449913 administered orally and continuously for 28 days.
- name
- PF-04449913
- type
- DRUG
- arm Group Labels
- Arm B (Phase 1B)
- description
- Decitabine given at 20 mg/m2 over 1 hour infusion for 5-days
- name
- Decitabine
- type
- DRUG
- arm Group Labels
- Arm C (Phase 1B)
- description
- PF-04449913 administered orally and continuously for 28 days
- name
- PF-04449913
- type
- DRUG
- arm Group Labels
- Arm C (Phase 1B)
- description
- Daunorubicin given using 60 mg/m2 for 3-days
- name
- Daunorubicin
- type
- DRUG
- arm Group Labels
- Arm C (Phase 1B)
- description
- Cytarabine 100 mg/m2 on days 1 through 7
- name
- Cytarabine
- type
- DRUG
- arm Group Labels
- P2 Fit (Phase 2 Single Arm)
- description
- PF-04449913 administered orally and continuously for 28 days
- name
- PF-04449913
- type
- DRUG
- arm Group Labels
- P2 Fit (Phase 2 Single Arm)
- description
- Daunorubicin given using 60 mg/m2 for 3-days
- name
- Daunorubicin
- type
- DRUG
- arm Group Labels
- P2 Fit (Phase 2 Single Arm)
- description
- Cytarabine 100 mg/m2 on days 1 through 7
- name
- Cytarabine
- type
- DRUG
- arm Group Labels
- P2 Unfit (Phase 2 Randomized)
- description
- PF-04449913 administered orally and continuously for 28 days (if randomized to receive PF-04449913)
- name
- PF-04449913
- type
- DRUG
- arm Group Labels
- P2 Unfit (Phase 2 Randomized)
- description
- Low dose ARA-C (LDAC) administered at 20 mg SQ, BID on Days 1 through 10.
- name
- Low dose ARA-C (LDAC)
- type
- DRUG
Study design
- allocation
- RANDOMIZED
- masking Info
- masking
- NONE
- primary Purpose
- TREATMENT
Enrollment
- count
- 255
- type
- ACTUAL
Registered outcome plans (not posted results)
- primary Outcomes
- description
- 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.
- measure
- Number of Participants With Dose-limiting Toxicities (DLTs) at Phase 1B
- time Frame
- Arms A and B: Cycle 1, Day 1 to Day 28; Arm C: Cycle 1, Day -3 to Day 21 or to Day 28 depending on when the next chemotherapy cycle was started
- description
- 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.
- measure
- Percentage of Participants With Complete Response (CR) at Phase 2 Fit
- time Frame
- 4 years
- description
- 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.
- measure
- Overall Survival (OS) at Phase 2 Unfit
- time Frame
- Randomization to Follow-up (4 years)
- secondary Outcomes
- description
- 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.
- measure
- Overall Survival (OS) at Phase 1B
- time Frame
- First dose to Follow-up (4 years)
- description
- 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.
- measure
- Overall Survival (OS) at Phase 2 Fit
- time Frame
- First dose to Follow-up (4 years)
- description
- 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).
- measure
- Percentage of Participants With CR / Complete Response With Incomplete Blood Count Recovery (CRi) at Phase 1B
- time Frame
- 4 years
- description
- 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.
- measure
- Percentage of Participants With Complete Response (CR) at Phase 2 Unfit
- time Frame
- 4 years
- description
- 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).
- measure
- Percentage of Participants With Disease-specific Efficacy for Acute Myeloid Leukemia (AML) at Phase 2 Fit and Unfit
- time Frame
- 4 years
- description
- 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).
- measure
- Percentage of Participants With Disease-specific Efficacy for Myelodysplastic Syndrome (MDS) at Phase 2 Fit and Unfit
- time Frame
- 4 years
- measure
- 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 Frame
- Pre-dose, 0.5, 1, 2, 4, 6 and 24 hours post-dose on Cycle 1/Day 10 and Cycle 1/Day 21
- measure
- 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
- time Frame
- Pre-dose, 0.5, 1, 2, 4, 6 and 24 hours post-dose on Cycle 1/Day 10 and Cycle 1/Day 21
- measure
- 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
- time Frame
- Pre-dose, 0.5, 1, 2, 4, 6 and 24 hours post-dose on Cycle 1/Day 10 and Cycle 1/Day 21
- measure
- Cmax of Glasdegib in Participants Receiving Glasdegib and Decitabine at Phase 1B on Cycle 1/Day 10 and Cycle 2/Day 1
- time Frame
- Pre-dose, 0.5, 1, 2, 4, 6 and 24 hours post-dose on Cycle 1/Day 10; pre-dose, 0.5, 1, 2, 6 and 24 hours post-dose on Cycle 2/Day 1
- measure
- Tmax of Glasdegib in Participants Receiving Glasdegib and Decitabine at Phase 1B on Cycle 1/Day 10 and Cycle 2/Day 1
- time Frame
- Pre-dose, 0.5, 1, 2, 4, 6 and 24 hours post-dose on Cycle 1/Day 10; pre-dose, 0.5, 1, 2, 6 and 24 hours post-dose on Cycle 2/Day 1
- measure
- AUCtau of Glasdegib in Participants Receiving Glasdegib and Decitabine at Phase 1B on Cycle 1/Day 10 and Cycle 2/Day 1
- time Frame
- Pre-dose, 0.5, 1, 2, 4, 6 and 24 hours post-dose on Cycle 1/Day 10; pre-dose, 0.5, 1, 2, 6 and 24 hours post-dose on Cycle 2/Day 1
Full study description
- brief Summary
- 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.
Source references
- references
- citation
- Heuser M, Smith BD, Fiedler W, Sekeres MA, Montesinos P, Leber B, Merchant A, Papayannidis C, Perez-Simon JA, Hoang CJ, O'Brien T, Ma WW, Zeremski M, O'Connell A, Chan G, Cortes JE. Clinical benefit of glasdegib plus low-dose cytarabine in patients with de novo and secondary acute myeloid leukemia: long-term analysis of a phase II randomized trial. Ann Hematol. 2021 May;100(5):1181-1194. doi: 10.1007/s00277-021-04465-4. Epub 2021 Mar 19.
- pmid
- 33740113
- type
- DERIVED
- citation
- Lin S, Shaik N, Chan G, Cortes JE, Ruiz-Garcia A. An evaluation of overall survival in patients with newly diagnosed acute myeloid leukemia and the relationship with glasdegib treatment and exposure. Cancer Chemother Pharmacol. 2020 Oct;86(4):451-459. doi: 10.1007/s00280-020-04132-x. Epub 2020 Sep 3.
- pmid
- 32885274
- type
- DERIVED
- citation
- Cortes JE, Heidel FH, Fiedler W, Smith BD, Robak T, Montesinos P, Candoni A, Leber B, Sekeres MA, Pollyea DA, Ferdinand R, Ma WW, O'Brien T, O'Connell A, Chan G, Heuser M. Survival outcomes and clinical benefit in patients with acute myeloid leukemia treated with glasdegib and low-dose cytarabine according to response to therapy. J Hematol Oncol. 2020 Jul 14;13(1):92. doi: 10.1186/s13045-020-00929-8.
- pmid
- 32664995
- type
- DERIVED
- citation
- Cortes JE, Heidel FH, Hellmann A, Fiedler W, Smith BD, Robak T, Montesinos P, Pollyea DA, DesJardins P, Ottmann O, Ma WW, Shaik MN, Laird AD, Zeremski M, O'Connell A, Chan G, Heuser M. Randomized comparison of low dose cytarabine with or without glasdegib in patients with newly diagnosed acute myeloid leukemia or high-risk myelodysplastic syndrome. Leukemia. 2019 Feb;33(2):379-389. doi: 10.1038/s41375-018-0312-9. Epub 2018 Dec 16.
- pmid
- 30555165
- type
- DERIVED
- citation
- Cortes JE, Douglas Smith B, Wang ES, Merchant A, Oehler VG, Arellano M, DeAngelo DJ, Pollyea DA, Sekeres MA, Robak T, Ma WW, Zeremski M, Naveed Shaik M, Douglas Laird A, O'Connell A, Chan G, Schroeder MA. Glasdegib in combination with cytarabine and daunorubicin in patients with AML or high-risk MDS: Phase 2 study results. Am J Hematol. 2018 Nov;93(11):1301-1310. doi: 10.1002/ajh.25238. Epub 2018 Sep 9.
- pmid
- 30074259
- type
- DERIVED
- citation
- Savona MR, Pollyea DA, Stock W, Oehler VG, Schroeder MA, Lancet J, McCloskey J, Kantarjian HM, Ma WW, Shaik MN, Laird AD, Zeremski M, O'Connell A, Chan G, Cortes JE. Phase Ib Study of Glasdegib, a Hedgehog Pathway Inhibitor, in Combination with Standard Chemotherapy in Patients with AML or High-Risk MDS. Clin Cancer Res. 2018 May 15;24(10):2294-2303. doi: 10.1158/1078-0432.CCR-17-2824. Epub 2018 Feb 20.
- pmid
- 29463550
- type
- DERIVED
- see Also Links
- label
- To obtain contact information for a study center near you, click here.
Source notices and limitations
Discovery and provenance
- release id
- ctgov-registry-7ad944f6deaf1f5cd6122126
- edge id
- nct-edge-72051eb2456aa86a381a
- requested nct id
- NCT01546038
- primary nct id
- NCT01546038
- source kind
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- payload sha256
- 8a3f82369874f78cc658058ddde6e95d8db5d794afb4e764358b0926e3b7334c
- payload
- application numbers
- NDA210656
- clinical indication matching status
- not_inferred
- end exclusive
- true
- id
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- link basis
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- nct id
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Preserved source evidence · Not medical advice