GLAD-AML - Glasdegib (Pf-04449913) With Two Standard Deci... | NCT04051996

NCT04051996

Protocol Section

Identification Module

Results Section

Participant Flow Module

Annotation Section

No data available

No data is available for this block.

Document Section

Large Document Module

Derived Section

Miscellaneous Info Module

Status Module

Name	Class
Pfizer	INDUSTRY

Description Module

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
DAC5	Experimental	Glasdegib will be administered at the starting dose of 100 mg orally once daily and continuously in combination with either DAC5 (decitabine 20 mg/m2 IV on a 5-day schedule) or DAC10 (decitabine 20 mg/m2 IV on a 10-day schedule) as per randomization. Treatment will be administered in 28-day cycles.	Drug: Glasdegib Drug: Decitabine
DAC10	Experimental	Glasdegib will be administered at the starting dose of 100 mg orally once daily and continuously in combination with either DAC5 (decitabine 20 mg/m2 IV on a 5-day schedule) or DAC10 (decitabine 20 mg/m2 IV on a 10-day schedule) as per randomization. Treatment will be administered in 28-day cycles.	Drug: Glasdegib Drug: Decitabine

Name	Type	Description	Arm Group Labels	Other Names
Glasdegib	Drug	Glasdegib will be administered at the starting dose of 100 mg orally once daily.	DAC10 DAC5

Measure	Description	Time Frame
CR/CRi	The complete remission (CR) and complete remission with incomplete count recovery (CRi) combined rate will be defined by the 2017 European LeukemiaNet (ELN) AML response criteria.	Up to 2 years

Measure	Description	Time Frame
OS	Overall survival (OS) is defined as the time from date of first study treatment to date of death due to any cause.	Up to 2 years
EFS	Event-free survival (EFS) will be monitored up to 2 years.

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Patients must have a morphologically-confirmed diagnosis of AML according to WHO 2016 classification with poor-risk disease as defined by the cytogenetic or molecular abnormalities (excluding FLT3-mutated AML).
Eastern Cooperative Oncology Group (ECOG) Performance Status ≤2.
Adequate Renal Function:

a. Calculated creatinine clearance (determined by MDRD) ≥50mL/min/1.73m2, or serum creatinine <1.5x upper limit of normal (ULN);
Adequate Liver Function:
1. Total serum bilirubin ≤ 2.0 x ULN (unless the bilirubin is principally unconjugated and there is strong suspicion of sub-clinical hemolysis or the patient has documented Gilbert's disease);
2. Aspartate transaminase (AST) and Alanine transaminase (ALT) ≤ 3.0 x ULN;
3. Alkaline phosphatase ≤ 3.0 x ULN.
Serum or urine pregnancy test (for female patients of childbearing potential) with a minimum sensitivity of 25 IU/L or equivalent units of human chorionic gonadotropin (HCG) negative at screening.
Males and female patients both of childbearing potential and at risk for pregnancy must agree to use two highly effective method(s) of contraception throughout the study and for 180 days after the last dose of decitabine and the last dose of glasdegib, whichever occurs later.
Female patients who are not of childbearing potential (i.e. meet at least 1 of the following criteria):
1. Have undergone a documented hysterectomy and/or bilateral oophorectomy;
2. Have medically confirmed ovarian failure;
3. Have achieved postmenopausal status, defined as follows: cessation of regular menses for at least 12 consecutive months with no alternative pathological or physiological cause; status may be confirmed by having a serum follicle stimulating hormone (FSH) level within the laboratory's reference range for postmenopausal women.

Exclusion Criteria:

Patients who are candidates for and willing to receive intensive induction chemotherapy.
Prior use of a hypomethylating agent.
Prior use of cytotoxic chemotherapy for any myeloid malignancy (prior immunosuppressive therapy is permitted provided that treatment is stopped within 8 weeks from study entry; hydroxyurea is allowed through the end of cycle 1 on study).
Previous hematopoietic stem cell transplant.
Prior treatment with a licensed or experimental smoothened inhibitor (SMOi) and/or hypomethylating agent (HMA).
Participation in a clinical study involving an investigational drug(s) (Phases 1-4) within 4 weeks prior to study entry or within 5 half-lives of the investigational agent, whichever is greater.
Major surgery or radiation within 12 weeks prior to study entry.
Patients known to be refractory to platelet or packed red cell transfusions as per institutional guidelines, or who are known to refuse or who are likely to refuse blood product support.
Treatment with hematopoietic growth factors including: erythropoietin, granulocyte colony stimulating factor (G-CSF), and granulocyte macrophage colony stimulating factor (GM-CSF), or thrombopoietin receptor agonists within 3 weeks prior to study entry.
Any ongoing medical condition requiring chronic use of moderate to high dose steroids (defined as ≥10 mg/day of prednisone or equipotent dose of another corticosteroid).
Any anti-cancer treatment within 2 weeks prior to study entry (including hydroxyurea as above).
Current use or anticipated requirement for drugs that are known moderate to strong CYP3A4 inducers (Appendix 2).
Presence of concurrent active malignancy requiring active systemic therapy
Patients with known active, uncontrolled bacterial, fungal or viral infection, including hepatitis B (HBV), hepatitis C (HCV), known human immunodeficiency virus (HIV), or acquired immunodeficiency syndrome (AIDS) related illness.
Known uncontrolled central nervous system (CNS) involvement.
Poorly-controlled active medical conditions that as per investigator judgement would interfere with the conduct of the study.
Active cardiac dysrhythmias of NCI CTCAE Grade ≥2 (e.g. atrial fibrillation) or QTcF interval >470 msec.
Pregnant or breastfeeding female patients.

Name	Affiliation	Role
Amer M Zeidan, MBBS	Yale University - MEDCCC Hematology-Section	Principal Investigator

Facility	Status	City	State	ZIP	Country	Contacts
Yale Cancer Center/Smilow		New Haven	Connecticut	06511	United States

Arm/Group Information

ID	Title	Description
FG000	DAC5	Glasdegib will be administered at the starting dose of 100 mg orally once daily and continuously in combination with either DAC5 (decitabine 20 mg/m2 IV on a 5-day schedule) or DAC10 (decitabine 20 mg/m2 IV on a 10-day schedule) as per randomization. Treatment will be administered in 28-day cycles. Glasdegib: Glasdegib will be administered at the starting dose of 100 mg orally once daily. Decitabine: Decitabine will be administered per local label and will be administered by IV infusion at a dose of 20 mg/m2/day for either 5 days or 10 days as determined by randomization. Each cycle will be every 28 days.
FG001	DAC10	Glasdegib will be administered at the starting dose of 100 mg orally once daily and continuously in combination with either DAC5 (decitabine 20 mg/m2 IV on a 5-day schedule) or DAC10 (decitabine 20 mg/m2 IV on a 10-day schedule) as per randomization. Treatment will be administered in 28-day cycles. Glasdegib: Glasdegib will be administered at the starting dose of 100 mg orally once daily. Decitabine: Decitabine will be administered per local label and will be administered by IV infusion at a dose of 20 mg/m2/day for either 5 days or 10 days as determined by randomization. Each cycle will be every 28 days.

Baseline Characteristics Module

Arm/Group Information

ID	Title	Description
BG000	DAC5	Glasdegib will be administered at the starting dose of 100 mg orally once daily and continuously in combination with either DAC5 (decitabine 20 mg/m2 IV on a 5-day schedule) or DAC10 (decitabine 20 mg/m2 IV on a 10-day schedule) as per randomization. Treatment will be administered in 28-day cycles. Glasdegib: Glasdegib will be administered at the starting dose of 100 mg orally once daily. Decitabine: Decitabine will be administered per local label and will be administered by IV infusion at a dose of 20 mg/m2/day for either 5 days or 10 days as determined by randomization. Each cycle will be every 28 days.

Units	Counts
Participants	BG000

Title	Description	Population Description	Parameter Type	Dispersion Type	Unit of Measure	Calculate Percentage	Denominator Units Selected	Denominators	Classes
Age, Continuous

Outcome Measures Module

Outcome Measures

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

CR/CRi

The complete remission (CR) and complete remission with incomplete count recovery (CRi) combined rate will be defined by the 2017 European LeukemiaNet (ELN) AML response criteria.

Only 1 patient was enrolled in the study prior to termination and therefore would be identified through presenting these characteristics.

Posted

Up to 2 years

ID	Title	Description
OG000	DAC5	Glasdegib will be administered at the starting dose of 100 mg orally once daily and continuously in combination with either DAC5 (decitabine 20 mg/m2 IV on a 5-day schedule) or DAC10 (decitabine 20 mg/m2 IV on a 10-day schedule) as per randomization. Treatment will be administered in 28-day cycles. Glasdegib: Glasdegib will be administered at the starting dose of 100 mg orally once daily. Decitabine: Decitabine will be administered per local label and will be administered by IV infusion at a dose of 20 mg/m2/day for either 5 days or 10 days as determined by randomization. Each cycle will be every 28 days.

Adverse Events Module

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	DAC5	Glasdegib will be administered at the starting dose of 100 mg orally once daily and continuously in combination with either DAC5 (decitabine 20 mg/m2 IV on a 5-day schedule) or DAC10 (decitabine 20 mg/m2 IV on a 10-day schedule) as per randomization. Treatment will be administered in 28-day cycles. Glasdegib: Glasdegib will be administered at the starting dose of 100 mg orally once daily. Decitabine: Decitabine will be administered per local label and will be administered by IV infusion at a dose of 20 mg/m2/day for either 5 days or 10 days as determined by randomization. Each cycle will be every 28 days.

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot_SAP	Yes	Yes	No	Study Protocol and Statistical Analysis Plan	Jul 17, 2020	Sep 15, 2021	Prot_SAP_000.pdf
ICF	No	No	Yes	Informed Consent Form	Jul 17, 2020	Sep 15, 2021	ICF_001.pdf

ID	Term
D007951	Leukemia, Myeloid
D007938	Leukemia
D009370	Neoplasms by Histologic Type
D009369	Neoplasms

ID	Term
D001374	Azacitidine
D001372	Aza Compounds
D009930	Organic Chemicals
D003562	Cytidine

ID	Term
C000592580	glasdegib
D000077209	Decitabine