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ACUTE MYELOID LEUKEMIAPhase 2NCT04051996

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

A Phase 2 study testing Glasdegib and Decitabine in people with ACUTE MYELOID LEUKEMIA, run by Yale University at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
ACUTE MYELOID LEUKEMIA
What is being tested?
Glasdegib and Decitabine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
1 participants
Where
1 siteUnited States
Study dates
6 Dec 2019to 9 Jun 2020
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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:
  • Calculated creatinine clearance (determined by MDRD) ≥50mL/min/1.73m2, or serum creatinine <1.5x upper limit of normal (ULN);
  • Adequate Liver Function:
  • 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);
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  • Aspartate transaminase (AST) and Alanine transaminase (ALT) ≤ 3.0 x ULN;
  • 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):
  • Have undergone a documented hysterectomy and/or bilateral oophorectomy;
  • Have medically confirmed ovarian failure;
  • 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.

Who cannot join

  • 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.
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  • 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.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Yale Cancer Center/Smilow

    New Haven, Connecticut, 06511

Other trials in United States

About this study

Official title: 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)

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.

Read the 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.

Being tested
Glasdegib, Decitabine
Medical subject headings
Leukemia, Myeloid, Acute

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • GlasdegibDrug

    Glasdegib will be administered at the starting dose of 100 mg orally once daily.

  • DecitabineDrug

    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 groups in NCT04051996
Study groupRoleWhat they receive
DAC5ExperimentalGlasdegib 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.
Receives: Drug: Glasdegib; Drug: Decitabine
DAC10ExperimentalGlasdegib 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.
Receives: Drug: Glasdegib; Drug: Decitabine

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: Up to 2 years

Secondary outcomes (6)

  1. OS

    Overall survival (OS) is defined as the time from date of first study treatment to date of death due to any cause.

    Measured: Up to 2 years

  2. EFS

    Event-free survival (EFS) will be monitored up to 2 years.

    Measured: Up to 2 years

  3. RFS

    Relapse-free survival (RFS) will be monitored up to 2 years.

    Measured: Up to 2 years

  4. Time to CR/CRi

    The time to complete remission (CR) and complete remission with incomplete count recovery (CRi) will be collected as a secondary outcome.

    Measured: Up to 2 years

  5. Duration of CR/CRi

    The duration of complete remission (CR) and complete remission with incomplete count recovery (CRi) will be collected as a secondary outcome.

    Measured: Up to 2 years

  6. Bone Marrow Mutational Clearance

    Bone marrow mutational clearance of frequently-mutated genes in AML (e.g. NPM1, CEBPA, DNMT3A, RUNX1, TET2, IDH1/2) via next-generation DNA sequencing will be monitored up to 2 years.

    Measured: Up to 2 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted9 Aug 2019
  2. Study start6 Dec 2019
  3. Primary completion9 Jun 2020
  4. Study completion9 Jun 2020

Why it stopped: Unable to accrue patients following COVID-19 study pause.

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Single blind
Who is masked
Participant
Enrolment
1 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04051996
Sponsor's protocol ID
2000024738
Status last verified
Sep 2021
First submitted
7 Aug 2019
Last updated
15 Oct 2021
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Glasdegib and Decitabine in people with ACUTE MYELOID LEUKEMIA, run by Yale University at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 14 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 15 Oct 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 15 Oct 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

CR/CRi (time frame: Up to 2 years). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04051996.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Oct 2021.

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