GLAD-AML - Glasdegib (Pf-04449913) With Two Standard Decitabine Regimens for Older Patients With Poor-risk Acute Myeloid Leukemia

NCT04051996

Last updated date
Study Location
Yale Cancer Center/Smilow
New Haven, Connecticut, 06511, United States
Contact
(203) 785-5573

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Eligibility Criteria
condition
The disease, disorder, syndrome, illness, or injury that is being studied.
ACUTE MYELOID LEUKEMIA
Sex
Females and Males
Age
Pediatric Trials: 0-17 Years
Adult Trials: 18+ Years
18 + years
Inclusion Criteria
The factors, or reasons, that allow a person to participate in a clinical study.
Show details

- 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
The factors, or reasons, that prevent a person from participating in a clinical study.
Show details


- 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.

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Advanced Information
Descriptive Information
Brief Title  ICMJE GLAD-AML - Glasdegib (Pf-04449913) With Two Standard Decitabine Regimens for Older Patients With Poor-risk Acute Myeloid Leukemia
Official Title  ICMJE A Randomized, Parallel-arm, Phase 2 Clinical Trial of the Combination of Glasdegib (Pf-04449913) With Two Standard Decitabine Regimens for Older Patients With Poor-risk Acute Myeloid Leukemia Who Are Unfit for or Refuse Intensive Chemotherapy (GLAD-AML)
Brief Summary This multi-center, randomized phase 2 study is designed to evaluate the complete remission (including complete remission with incomplete count recovery) rates of glasdegib in combination with either decitabine on a 5-day or 10-day schedule in patients with newly-diagnosed poor-risk AML who either refuse or are ineligible for intensive therapy.
Detailed Description

The primary objective of this multi-center, randomized phase 2 study is to determine the response rates, complete remission (CR) and complete remission with incomplete count recovery (CRi), of glasdegib/DAC5 and glasdegib/DAC10 in patients with newly-diagnosed PrAML.

There are two secondary objectives for this study. The first secondary objective is to evaluate the toxicity and safety profiles of glasdegib/DAC5 and glasdegib/DAC10 in patients with newly-diagnosed PrAML. The other secondary objective is to determine the event-free survival (EFS), relapse-free survival (RFS), overall survival (OS), duration of response, bone marrow mutational clearance, and remission clonality of glasdegib/DAC5 and glasdegib/DAC10 in patients with newly-diagnosed PrAML.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Participant)
Primary Purpose: Treatment
Condition  ICMJE ACUTE MYELOID LEUKEMIA
Intervention  ICMJE
  • Drug: Glasdegib
    Glasdegib will be administered at the starting dose of 100 mg orally once daily.
  • Drug: 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.
Study Arms  ICMJE
  • Experimental: 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.
    Interventions:
    • Drug: Glasdegib
    • Drug: Decitabine
  • Experimental: 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.
    Interventions:
    • Drug: Glasdegib
    • Drug: Decitabine
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: August 7, 2019)
46
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE September 15, 2022
Estimated Primary Completion Date September 15, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study:All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Alexander Hoslet(203) 785-5573[email protected]
Contact: Tara McPartland, MSW, MPH(203) 737-7173[email protected]
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04051996
Other Study ID Numbers  ICMJE 2000024738
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD:No
Responsible Party Amer Zeidan, Yale University
Study Sponsor  ICMJE Yale University
Collaborators  ICMJE Pfizer
Investigators  ICMJE
Principal Investigator:Amer M Zeidan, MBBSYale University - MEDCCC Hematology-Section
PRS Account Yale University
Verification Date August 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP