Recurrent Acute Myeloid LeukemiaPhase 1NCT04655391

Glasdegib-Based Treatment Combinations for the Treatment of Patients With Relapsed Acute Myeloid Leukemia Who Have Undergone Hematopoietic Cell Transplantation

A Phase 1 study testing Bosutinib Monohydrate, Decitabine and Enasidenib Mesylate in people with Recurrent Acute Myeloid Leukemia, run by City of Hope Medical Center at 1 site in United States.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record

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Trial summary

Who is it for?: Ages 18 years and older
Conditions the study is for: Recurrent Acute Myeloid Leukemia
What is being tested?: Bosutinib Monohydrate, Decitabine and Enasidenib Mesylate
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 0 participants
Where: 1 siteUnited States
Study dates: 25 Jun 2022to 15 Dec 2023
Phase: Phase 1
Are there results?: None posted in the registry

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

MOLECULAR DIAGNOSIS SEGMENT: Documented informed consent of the participant and/or legally authorized representative
MOLECULAR DIAGNOSIS SEGMENT: Age: >= 18 years on the day of signing informed consent
MOLECULAR DIAGNOSIS SEGMENT: Eastern Cooperative Oncology Group (ECOG) =< 2
MOLECULAR DIAGNOSIS SEGMENT: Patients with histologically confirmed acute myeloid leukemia (AML), according to World Health Organization (WHO) criteria, with relapsed disease after allogeneic hematopoietic cell transplantation (alloHCT)
Patients with non-central nervous system (CNS) extramedullary disease may be included if they also have marrow disease
Patients with acute promyelocytic leukemia (APL) will not be eligible

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MOLECULAR DIAGNOSIS SEGMENT: Fully recovered from the acute toxic effects (except alopecia) to =< grade 1 of prior anti-cancer therapy
MOLECULAR DIAGNOSIS SEGMENT: Total bilirubin =< 2 x ULN (unless has Gilbert's disease) (to be performed within 28 days prior to day 1 of protocol therapy unless otherwise stated in the study calendar)
MOLECULAR DIAGNOSIS SEGMENT: Aspartate aminotransferase (AST)=< 2 x ULN (to be performed within 28 days prior to day 1 of protocol therapy unless otherwise stated in the study calendar)
MOLECULAR DIAGNOSIS SEGMENT: Alanine aminotransferase (ALT) =< 2 x ULN (to be performed within 28 days prior to day 1 of protocol therapy unless otherwise stated in the study calendar) (to be performed within 28 days prior to day 1 of protocol therapy unless otherwise stated in the study calendar)
MOLECULAR DIAGNOSIS SEGMENT: Creatinine clearance of >= 50 mL/min per 24-hour urine test or the Cockcroft-Gault formula (to be performed within 28 days prior to day 1 of protocol therapy unless otherwise stated in the study calendar)
MOLECULAR DIAGNOSIS SEGMENT: If not receiving anticoagulants: international normalized ratio (INR) OR prothrombin time (PT) =< 1.5 x ULN. If on anticoagulant therapy: PT must be within therapeutic range of intended use of anticoagulants (to be performed within 28 days prior to day 1 of protocol therapy unless otherwise stated in the study calendar)
MOLECULAR DIAGNOSIS SEGMENT: If not receiving anticoagulants: activated partial thromboplastin Time (aPTT) =<1.5 x ULN. If on anticoagulant therapy: aPTT must be within therapeutic range of intended use of anticoagulants (to be performed within 28 days prior to day 1 of protocol therapy unless otherwise stated in the study calendar)
MOLECULAR DIAGNOSIS SEGMENT: Left ventricular ejection fraction (LVEF) >= 45% (to be performed within 28 days prior to day 1 of protocol therapy unless otherwise stated in the study calendar)
Note: Echocardiogram to be performed within 28 days prior to day 1 of protocol therapy
MOLECULAR DIAGNOSIS SEGMENT: Corrected QT (QTc) =< 470 milliseconds (ms) (to be performed within 28 days prior to day 1 of protocol therapy unless otherwise stated in the study calendar)
Note: Electrocardiogram (ECG) to be performed within 14 days prior to day 1 of protocol therapy
MOLECULAR DIAGNOSIS SEGMENT: Women of childbearing potential (WOCBP): Negative urine or serum pregnancy test. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required (to be performed within 28 days prior to day 1 of protocol therapy unless otherwise stated in the study calendar)
MOLECULAR DIAGNOSIS SEGMENT: Agreement by females and males of childbearing potential to use an effective method of birth control or abstain from heterosexual activity from 4 weeks prior to first dose of treatment throughout the study treatment period and 1 month (females) or 1 month (males) from the last dose of study drug
Childbearing potential is defined as not being surgically sterilized (men and women) or have not been free from menses for > 1 year (women only)
CHAPTER 1: Documented informed consent of the participant and/or legally authorized representative
CHAPTER 1: Age: >= 18 years on the day of signing informed consent
CHAPTER 1: ECOG =< 2
CHAPTER 1: Patients with histologically confirmed AML, according to WHO criteria, with relapsed disease after alloHCT
Patients with non-central nervous system (CNS) extramedullary disease may be included if they also have marrow disease
Patients with acute promyelocytic leukemia (APL) will not be eligible
CHAPTER 1: Fully recovered from the acute toxic effects (except alopecia) to =< grade 1 of prior anti-cancer therapy
CHAPTER 1: White blood cell count less than 25 x 10^9 /L prior to initiation of venetoclax. Cytoreduction with hydroxyurea prior to treatment and/or up to 1 week after start of this treatment arm may be required (to be performed within 28 days prior to day 1 of protocol therapy unless otherwise stated in the study calendar)
CHAPTER 1: Total bilirubin =< 2 x ULN (unless has Gilbert's disease) (to be performed within 28 days prior to day 1 of protocol therapy unless otherwise stated in the study calendar)
CHAPTER 1: AST =< 2 x ULN (to be performed within 28 days prior to day 1 of protocol therapy unless otherwise stated in the study calendar)
CHAPTER 1: ALT =< 2 x ULN (to be performed within 28 days prior to day 1 of protocol therapy unless otherwise stated in the study calendar)
CHAPTER 1: Creatinine clearance of >= 50 mL/min per 24-hour urine test or the Cockcroft-Gault formula (to be performed within 28 days prior to day 1 of protocol therapy unless otherwise stated in the study calendar)
CHAPTER 1: If not receiving anticoagulants: International normalized ratio (INR) OR prothrombin time (PT) =< 1.5 x ULN. If on anticoagulant therapy: PT must be within therapeutic range of intended use of anticoagulants (to be performed within 28 days prior to day 1 of protocol therapy unless otherwise stated in the study calendar)
CHAPTER 1: If not receiving anticoagulants: Activated partial thromboplastin time (aPTT) =< 1.5 x ULN If on anticoagulant therapy: aPTT must be within therapeutic range of intended use of anticoagulants (to be performed within 28 days prior to day 1 of protocol therapy unless otherwise stated in the study calendar)
CHAPTER 1: QTc =< 470 milliseconds (ms) (to be performed within 28 days prior to day 1 of protocol therapy unless otherwise stated in the study calendar)
Note: ECG to be performed within 14 days prior to day 1 of protocol therapy
CHAPTER 1: Women of childbearing potential (WOCBP): negative urine or serum pregnancy test. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
CHAPTER 1: Agreement by females and males of childbearing potential* to use an effective method of birth control or abstain from heterosexual activity from 4 weeks prior to first dose of treatment throughout the study treatment period and 6 months (females) or 3 months (males) from the last dose of study drug
Childbearing potential is defined as not being surgically sterilized (men and women) or have not been free from menses for > 1 year (women only)
CHAPTER 2: Documented informed consent of the participant and/or legally authorized representative
CHAPTER 2: Age: >= 18 years on the day of signing informed consent
CHAPTER 2: ECOG =< 2
CHAPTER 2: Patients with histologically confirmed AML, according to WHO criteria, with relapsed disease after alloHCT
Patients with non-central nervous system (CNS) extramedullary disease may be included if they also have marrow disease
Patients with acute promyelocytic leukemia (APL) will not be eligible
CHAPTER 2: Patients with a confirmed susceptible FLT3 mutation (m) (internal tandem duplications (ITD), tyrosine kinase domain (TKD) mutations D835 or I836), or AXL variant expression
CHAPTER 2: Fully recovered from the acute toxic effects (except alopecia) to =< grade 1 of prior anti-cancer therapy
CHAPTER 2: Total bilirubin =< 2 x ULN (unless has Gilbert's disease) (to be performed within 28 days prior to day 1 of protocol therapy unless otherwise stated in the study calendar)
CHAPTER 2: AST =< 2 x ULN (to be performed within 28 days prior to day 1 of protocol therapy unless otherwise stated in the study calendar)
CHAPTER 2: ALT =< 2 x ULN (to be performed within 28 days prior to day 1 of protocol therapy unless otherwise stated in the study calendar)
CHAPTER 2: Creatinine clearance of >= 50 mL/min per 24-hour urine test or the Cockcroft-Gault formula (to be performed within 28 days prior to day 1 of protocol therapy unless otherwise stated in the study calendar)
CHAPTER 2: If not receiving anticoagulants: International normalized ratio (INR) OR prothrombin time (PT) =< 1.5 x ULN. If on anticoagulant therapy: PT must be within therapeutic range of intended use of anticoagulants (to be performed within 28 days prior to day 1 of protocol therapy unless otherwise stated in the study calendar)
CHAPTER 2: If not receiving anticoagulants: Activated partial thromboplastin time (aPTT) =< 1.5 x ULN If on anticoagulant therapy: aPTT must be within therapeutic range of intended use of anticoagulants (to be performed within 28 days prior to day 1 of protocol therapy unless otherwise stated in the study calendar)
CHAPTER 2: QTc =< 470 milliseconds (ms) (to be performed within 28 days prior to day 1 of protocol therapy unless otherwise stated in the study calendar)
Note: ECG to be performed within 14 days prior to day 1 of protocol therapy
CHAPTER 2: Women of childbearing potential (WOCBP): negative urine or serum pregnancy test. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
CHAPTER 2: Agreement by females and males of childbearing potential* to use an effective method of birth control or abstain from heterosexual activity from 4 weeks prior to first dose of treatment throughout the study treatment period and 6 months (females) or 4 months (males) from the last dose of study drug
Childbearing potential is defined as not being surgically sterilized (men and women) or have not been free from menses for > 1 year (women only)
CHAPTER 3: Documented informed consent of the participant and/or legally authorized representative
CHAPTER 3: Age: >= 18 years on the day of signing informed consent
CHAPTER 3: ECOG =< 2
CHAPTER 3: Patients with histologically confirmed AML, according to WHO criteria, with relapsed disease after alloHCT
Patients with non-central nervous system (CNS) extramedullary disease may be included if they also have marrow disease
Patients with acute promyelocytic leukemia (APL) will not be eligible
CHAPTER 3: Patients with a confirmed susceptible BCR-ABL1 gene fusion
CHAPTER 3: Fully recovered from the acute toxic effects (except alopecia) to =< grade 1 of prior anti-cancer therapy
CHAPTER 3: Total bilirubin =< 2 x ULN (unless has Gilbert's disease) (to be performed within 28 days prior to day 1 of protocol therapy unless otherwise stated in the study calendar)
CHAPTER 3: AST =< 2 x ULN (to be performed within 28 days prior to day 1 of protocol therapy unless otherwise stated in the study calendar)
CHAPTER 3: Creatinine clearance of >= 50 mL/min per 24-hour urine test or the Cockcroft-Gault formula (to be performed within 28 days prior to day 1 of protocol therapy unless otherwise stated in the study calendar)
CHAPTER 3: If not receiving anticoagulants: international normalized ratio (INR) OR prothrombin time (PT) =< 1.5 x ULN. If on anticoagulant therapy: PT must be within therapeutic range of intended use of anticoagulants (to be performed within 28 days prior to day 1 of protocol therapy unless otherwise stated in the study calendar)
CHAPTER 3: If not receiving anticoagulants: activated partial thromboplastin Time (aPTT) =<1.5 x ULN. If on anticoagulant therapy: aPTT must be within therapeutic range of intended use of anticoagulants (to be performed within 28 days prior to day 1 of protocol therapy unless otherwise stated in the study calendar)
CHAPTER 3: Left ventricular ejection fraction (LVEF) >= 45%
Note: Echocardiogram to be performed within 60 days prior to day 1 of protocol therapy
CHAPTER 3: QTc =< 470 milliseconds (ms) (to be performed within 28 days prior to day 1 of protocol therapy unless otherwise stated in the study calendar)
Note: ECG to be performed within 14 days prior to day 1 of protocol therapy
CHAPTER 3: Women of childbearing potential (WOCBP): Negative urine or serum pregnancy test. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required (to be performed within 28 days prior to day 1 of protocol therapy unless otherwise stated in the study calendar)
CHAPTER 3: Agreement by females and males of childbearing potential* to use an effective method of birth control or abstain from heterosexual activity from 4 weeks prior to first dose of treatment throughout the study treatment period and 1 month (females) and 1 month (males) from the last dose of study drug
Childbearing potential is defined as not being surgically sterilized (men and women) or have not been free from menses for > 1 year (women only)
CHAPTER 4: Documented informed consent of the participant and/or legally authorized representative
CHAPTER 4: Age: >= 18 years on the day of signing informed consent
CHAPTER 4: ECOG =< 2
CHAPTER 4: Patients with histologically confirmed AML, according to WHO criteria, with relapsed disease after alloHCT
Patients with non-central nervous system (CNS) extramedullary disease may be included if they also have marrow disease
Patients with acute promyelocytic leukemia (APL) will not be eligible
CHAPTER 4: Patients with a confirmed susceptible IDH1 mutation (R132)
CHAPTER 4: Fully recovered from the acute toxic effects (except alopecia) to =< grade 1 of prior anti-cancer therapy
CHAPTER 4: Total bilirubin =< 2 x ULN (unless has Gilbert's disease) (to be performed within 28 days prior to day 1 of protocol therapy unless otherwise stated in the study calendar)
CHAPTER 4: AST =< 2 x ULN (to be performed within 28 days prior to day 1 of protocol therapy unless otherwise stated in the study calendar)
CHAPTER 4: ALT =< 2 x ULN (to be performed within 28 days prior to day 1 of protocol therapy unless otherwise stated in the study calendar)
CHAPTER 4: Creatinine clearance of >= 50 mL/min per 24-hour urine test or the Cockcroft-Gault formula (to be performed within 28 days prior to day 1 of protocol therapy unless otherwise stated in the study calendar)
CHAPTER 4: If not receiving anticoagulants: International normalized ratio (INR) OR prothrombin time (PT) =< 1.5 x ULN. If on anticoagulant therapy: PT must be within therapeutic range of intended use of anticoagulants (to be performed within 28 days

Who cannot join

None listed.

Trial locations and contacts

1 site in 1 country.

United States1 site

City of Hope Meidcal Center
Duarte, California, 91010

Other trials in United States

About this study

Official title: A Pilot/Phase 1b Study of Glasdegib-Based Treatment Combinations in Adult Patients With Relapsed AML Post Allogeneic Hematopoietic Cell Transplantation

This phase Ib trial evaluates the best dose and effect of glasdegib in combination with venetoclax and decitabine, or gilteritinib, bosutinib, ivosidenib, or enasidenib in treating patients with acute myeloid leukemia that has come back (relapsed) after stem cell transplantation. Chemotherapy drugs, such as venetoclax and decitabine, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Glasdegib, bosutinib, ivosidenib, and enasidenib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Glasdegib inhibits the Sonic the Hedgehog gene. Venetoclax inhibits BCL-2 gene. Bosutinib is a tyrosine kinase inhibitor that inhibits BCR-ABL gene fusion. Ivosidenib inhibits isocitrate dehydrogenase-1 gene or IDH-1. Enasidenib inhibits isocitrate dehydrogenase-2 gene or IDH-2. This study involves an individualized approach that may allow doctors and researchers to more accurately predict which treatment plan works best for patients with relapsed acute myeloid leukemia.

Read the detailed description

PRIMARY OBJECTIVES:

Evaluate study feasibility through:

Ia. The ability to obtain a molecular diagnosis within 10 calendar days from study enrollment in at least 90% of participants. (Molecular Diagnosis Segment) Ib. The ability to make a treatment arm assignment within 14 calendar days from study enrollment in at least 90% of participants. (Molecular Diagnosis Segment) II. Assess the safety and tolerability of the drug combination by evaluation of toxicities including: type, frequency, severity, attribution, and duration of the toxicity. (Treatment Segment)

SECONDARY OBJECTIVES:

Determine the proportion of participants with successful sequencing by City of Hope (COH) Pathology among those with less than 10% blasts in the marrow aspirate. (Molecular Diagnosis Segment) II. Determine the proportion of participants with successful treatment arm registration based on Treatment Assignment Committee (TAC) assignment. (Molecular Diagnosis Segment) III. Assess the safety of monotherapy glasdegib by evaluation of toxicities including, type, frequency, severity and attribution. (Molecular Diagnosis Segment) IV. Obtain preliminary estimates of remission (complete response [CR] + CR with incomplete blood count recovery [CRi]) rate and duration of remission. (Treatment Segment)

EXPLORATORY OBJECTIVE:

Measure and characterize the leukemia stem cell (LSC) burden. (Treatment Segment)

OUTLINE: This is a dose escalation study of glasdegib maleate (glasdegib) followed by a dose-expansion study.

MOLECULAR DIAGNOSIS SEGMENT: Patients receive glasdegib orally (PO) once daily (QD) for at least 14 days until their acute myeloid leukemia (AML) TAC recommendation is made and they are either consented to a treatment arm in the Treatment Segment or go off study.

TREATMENT SEGMENT: Patients are assigned to 1 of 5 arms.

CHAPTER 1: Patients receive glasdegib PO QD on days 1-28, decitabine intravenously (IV) over 1 hour on days 1-5, and venetoclax PO QD on days 1-14. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity.

CHAPTER 2: Patients receive glasdegib PO QD and gilteritinib fumarate (gilteritinib) PO QD on days 1-28. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity.

CHAPTER 3: Patients receive glasdegib PO QD and bosutinib monohydrate (bosutinib) PO QD on days 1-28. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity.

CHAPTER 4: Patients receive glasdegib PO QD and ivosidenib PO QD on days 1-28. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity.

CHAPTER 5: Patients receive glasdegib PO QD and enasidenib mesylate (enasidenib) PO QD on days 1-28. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for 30 days.

Conditions: Recurrent Acute Myeloid Leukemia
Being tested: Bosutinib Monohydrate, Decitabine, Enasidenib Mesylate, Gilteritinib Fumarate, Glasdegib Maleate
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.

Bosutinib MonohydrateDrug
Also called 3-Quinolinecarbonitrile, 4-((2,4-Dichloro-5-methoxyphenyl)amino)-6-methoxy-7-(3-(4-methyl-1-piperazinyl)propoxy)-, Hydrate (1:1), Bosulif, SKI-606 Monohydrate
Given PO
DecitabineDrug
Also called 5-Aza-2''-deoxycytidine, Dacogen, Decitabine for Injection, Deoxyazacytidine
Given IV
Enasidenib MesylateDrug
Also called 2-Methyl-1-[(4-[6-(trifluoromethyl)pyridin-2-yl]-6-{[2-(trifluoromethyl)pyridin-4-yl]amino}-1,3,5-triazin-2-yl)amino]propan-2-ol Methanesulfonate, 2-Propanol, 2-Methyl-1-((4-(6-(trifluoromethyl)-2-pyridinyl)-6-((2-(trifluoromethyl)-4-pyridinyl)amino)-1,3,5-triazin-2-yl)amino)-, Methanesulfonate (1:1), AG-221 Mesylate, CC-90007
Given IV
Gilteritinib FumarateDrug
Also called ASP-2215 Hemifumarate, ASP2215 Hemifumarate, Gilteritinib Hemifumarate, Xospata
Given PO
Glasdegib MaleateDrug
Also called Daurismo, PF 04449913 Maleate
Given PO
IvosidenibDrug
Also called AG-120, Tibsovo
Given PO
VenetoclaxDrug
Also called ABT-0199, ABT-199, ABT199, GDC-0199
Given PO

Study groups in NCT04655391
Study group	Role	What they receive
Chapter 1 (glasdegib, decitabine, venetoclax)	Experimental	MOLECULAR DIAGNOSIS SEGMENT: Patients receive glasdegib PO QD for at least 14 days until their AML TAC recommendation is made and they are either consented to a treatment arm in the Treatment Segment or go off study. TREATMENT SEGMENT: Patients receive glasdegib PO QD on days 1-28,decitabine IV over 1 hour on days 1-5, and venetoclax PO QD on days 1-14. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. Receives: Drug: Decitabine; Drug: Glasdegib Maleate; Drug: Venetoclax
Chapter 2 (glasdegib, gilteritinib)	Experimental	MOLECULAR DIAGNOSIS SEGMENT: Patients receive glasdegib PO QD for at least 14 days until their AML TAC recommendation is made and they are either consented to a treatment arm in the Treatment Segment or go off study. TREATMENT SEGMENT: Patients receive glasdegib PO QD and gilteritinib PO QD on days 1-28. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. Receives: Drug: Gilteritinib Fumarate; Drug: Glasdegib Maleate
Chapter 3 (glasdegib, bosutinib)	Experimental	MOLECULAR DIAGNOSIS SEGMENT: Patients receive glasdegib PO QD for at least 14 days until their AML TAC recommendation is made and they are either consented to a treatment arm in the Treatment Segment or go off study. TREATMENT SEGMENT: Patients receive glasdegib PO QD and bosutinib PO QD on days 1-28. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. Receives: Drug: Bosutinib Monohydrate; Drug: Glasdegib Maleate
Chapter 4 (glasdegib, ivosidenib)	Experimental	MOLECULAR DIAGNOSIS SEGMENT: Patients receive glasdegib PO QD for at least 14 days until their AML TAC recommendation is made and they are either consented to a treatment arm in the Treatment Segment or go off study. TREATMENT SEGMENT: Patients receive glasdegib PO QD and ivosidenib PO QD on days 1-28. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. Receives: Drug: Glasdegib Maleate; Drug: Ivosidenib
Chapter 5 (glasdegib, enasidenib)	Experimental	MOLECULAR DIAGNOSIS SEGMENT: Patients receive glasdegib PO QD for at least 14 days until their AML TAC recommendation is made and they are either consented to a treatment arm in the Treatment Segment or go off study. TREATMENT SEGMENT: Patients receive glasdegib PO QD and enasidenib PO QD on days 1-28 .Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. Receives: Drug: Enasidenib Mesylate; Drug: Glasdegib Maleate

What is being measured

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

Ability to obtain a molecular diagnosis (Molecular Diagnosis Segment)
Outcome will be dichotomized based on return in =< 10 calendar days (Yes/No). Assessed by the proportion of successful participants.
Measured: From study enrollment to return of Molecular Diagnosis Report, assessed up to 30 days
Ability to make a treatment arm assignment by the Treatment Assignment Committee (TAC) (Molecular Diagnosis Segment)
Outcome will be dichotomized based on return in =< 14 calendar days (Yes/No). Assessed by the proportion of participants who receive treatment assignment from TAC.
Measured: From enrollment to treatment arm assignment by the TAC, assessed up to 30 days
Incidence of adverse events (Treatment Segment)
Toxicity will be graded according to the National Cancer Institute (NCI)-Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Safety will be based on the assessment of dose limiting toxicity during cycle 1 and cycle 2. Observed toxicities will be summarized in terms of type (organ affected or laboratory determination), severity, time of onset, duration, probable association with the study treatment and reversibility or outcome.
Measured: Up to 30 days

Secondary outcomes (5)

Proportion of patients with successful sequencing (Molecular Diagnosis Segment)
Successful sequencing is defined as passing quality control, and will be determined by City of Hope pathology among those with less than 20% blasts in the marrow aspirate.
Measured: Up to 30 days
Proportion of patients with successful treatment arm registration (Molecular Diagnosis Segment)
Successful placement defined as the enrollment of a participant into one of the treatment arms.
Measured: Up to 30 days
Incidence of adverse events (Molecular Diagnosis Segment)
Toxicity will be graded according to the NCI-CTCAE version 5.0. Safety will be based on the assessment of unacceptable toxicity during glasdegib monotherapy. Observed toxicities will be summarized in terms of type (organ affected or laboratory determination), severity, time of onset, duration, probable association with the study treatment and reversibility or outcome.
Measured: Up to 30 days
Overall response (Treatment Segment)
Response will be based on Dohner et al., 2017 criteria. Response dates recorded will be the date of the first of 2 successive bone marrows showing said response. For this trial, will assess the complete remission rate calculated as the percent of evaluable patients that have confirmed complete response (CR) or incomplete blood count recovery (CRi). 95% Clopper Pearson binomial confidence interval will be calculated. Response rates will also be explored based on number/type of prior therapy(ies).
Measured: Up to the date of the first of 2 successive bone marrows showing said response, assessed up to 30 days
Duration of remission (Treatment Segment)
Measured: Time from the first of two consecutive bone marrow aspirates showing CR or CRi until such time as the bone marrow or peripheral blood mononuclear cells shows signs of relapse, assessed up to 30 days

Timeline

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

25 Jun 202215 Dec 2023

First posted7 Dec 2020
Study start25 Jun 2022 (estimated)
Primary completion15 Dec 2023 (estimated)
Study completion15 Dec 2023 (estimated)

Why it stopped: Drug availability

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Other trials for Recurrent Acute Myeloid LeukemiaStudies of the same condition, open and under way.
More trials run by City of Hope Medical CenterThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

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 1
Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 0 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT04655391
Sponsor's protocol ID: 20456
Other IDs: NCI-2020-10595, 20456, P30CA033572
Status last verified: Jun 2022
First submitted: 23 Nov 2020
Last updated: 9 Jun 2022
Results posted: No
Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 9 Jun 2022. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Pilot/Phase 1b Study of Glasdegib-Based Treatment Combinations in Adult Patients With Relapsed AML Post Allogeneic Hematopoietic Cell Transplantation
ClinicalTrials.gov ID: NCT04655391
Acronym / sponsor ID: 20456
Conditions: Recurrent Acute Myeloid Leukemia
Phase: Phase 1
Study type: Interventional
Recruitment status: WithdrawnReason stopped: Drug availability
Enrolment: 0 participants (actual)
Lead sponsor: City of Hope Medical CenterUniversity, hospital or other
Collaborators: National Cancer Institute (NCI)
Study start: 25 Jun 2022 (estimated)
Primary completion: 15 Dec 2023 (estimated)
Study completion: 15 Dec 2023 (estimated)
First posted: 7 Dec 2020 (actual)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

PRIMARY OBJECTIVES:

Evaluate study feasibility through:

SECONDARY OBJECTIVES:

Determine the proportion of participants with successful sequencing by City of Hope (COH) Pathology among those with less than 10% blasts in the marrow aspirate. (Molecular Diagnosis Segment) II. Determine the proportion of participants with successful treatment arm registration based on Treatment Assignment Committee (TAC) assignment. (Molecular Diagnosis Segment) III. Assess the safety of monotherapy glasdegib by evaluation of toxicities including, type, frequency, severity and attribution. (Molecular Diagnosis Segment) IV. Obtain preliminary estimates of remission (complete response [CR] + CR with incomplete blood count recovery [CRi]) rate and duration of remission. (Treatment Segment)

EXPLORATORY OBJECTIVE:

Measure and characterize the leukemia stem cell (LSC) burden. (Treatment Segment)

OUTLINE: This is a dose escalation study of glasdegib maleate (glasdegib) followed by a dose-expansion study.

TREATMENT SEGMENT: Patients are assigned to 1 of 5 arms.

CHAPTER 4: Patients receive glasdegib PO QD and ivosidenib PO QD on days 1-28. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for 30 days.

Study design

Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 5

Arm	Type	Receives
Chapter 1 (glasdegib, decitabine, venetoclax)	Experimental	Drug: Decitabine, Drug: Glasdegib Maleate, Drug: VenetoclaxMOLECULAR DIAGNOSIS SEGMENT: Patients receive glasdegib PO QD for at least 14 days until their AML TAC recommendation is made and they are either consented to a treatment arm in the Treatment Segment or go off study. TREATMENT SEGMENT: Patients receive glasdegib PO QD on days 1-28,decitabine IV over 1 hour on days 1-5, and venetoclax PO QD on days 1-14. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity.
Chapter 2 (glasdegib, gilteritinib)	Experimental	Drug: Gilteritinib Fumarate, Drug: Glasdegib MaleateMOLECULAR DIAGNOSIS SEGMENT: Patients receive glasdegib PO QD for at least 14 days until their AML TAC recommendation is made and they are either consented to a treatment arm in the Treatment Segment or go off study. TREATMENT SEGMENT: Patients receive glasdegib PO QD and gilteritinib PO QD on days 1-28. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity.
Chapter 3 (glasdegib, bosutinib)	Experimental	Drug: Bosutinib Monohydrate, Drug: Glasdegib MaleateMOLECULAR DIAGNOSIS SEGMENT: Patients receive glasdegib PO QD for at least 14 days until their AML TAC recommendation is made and they are either consented to a treatment arm in the Treatment Segment or go off study. TREATMENT SEGMENT: Patients receive glasdegib PO QD and bosutinib PO QD on days 1-28. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity.
Chapter 4 (glasdegib, ivosidenib)	Experimental	Drug: Glasdegib Maleate, Drug: IvosidenibMOLECULAR DIAGNOSIS SEGMENT: Patients receive glasdegib PO QD for at least 14 days until their AML TAC recommendation is made and they are either consented to a treatment arm in the Treatment Segment or go off study. TREATMENT SEGMENT: Patients receive glasdegib PO QD and ivosidenib PO QD on days 1-28. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity.
Chapter 5 (glasdegib, enasidenib)	Experimental	Drug: Enasidenib Mesylate, Drug: Glasdegib MaleateMOLECULAR DIAGNOSIS SEGMENT: Patients receive glasdegib PO QD for at least 14 days until their AML TAC recommendation is made and they are either consented to a treatment arm in the Treatment Segment or go off study. TREATMENT SEGMENT: Patients receive glasdegib PO QD and enasidenib PO QD on days 1-28 .Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity.

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (91 listed)

MOLECULAR DIAGNOSIS SEGMENT: Documented informed consent of the participant and/or legally authorized representative
MOLECULAR DIAGNOSIS SEGMENT: Age: >= 18 years on the day of signing informed consent
MOLECULAR DIAGNOSIS SEGMENT: Eastern Cooperative Oncology Group (ECOG) =< 2
MOLECULAR DIAGNOSIS SEGMENT: Patients with histologically confirmed acute myeloid leukemia (AML), according to World Health Organization (WHO) criteria, with relapsed disease after allogeneic hematopoietic cell transplantation (alloHCT)
MOLECULAR DIAGNOSIS SEGMENT: Fully recovered from the acute toxic effects (except alopecia) to =< grade 1 of prior anti-cancer therapy

Key exclusion criteria (0 listed)

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Bosutinib MonohydrateAlso: 3-Quinolinecarbonitrile, 4-((2,4-Dichloro-5-methoxyphenyl)amino)-6-methoxy-7-(3-(4-methyl-1-piperazinyl)propoxy)-, Hydrate (1:1), Bosulif, SKI-606 MonohydrateGiven PO	Drug	Chapter 3 (glasdegib, bosutinib)
DecitabineAlso: 5-Aza-2''-deoxycytidine, Dacogen, Decitabine for Injection, DeoxyazacytidineGiven IV	Drug	Chapter 1 (glasdegib, decitabine, venetoclax)
Enasidenib MesylateAlso: 2-Methyl-1-[(4-[6-(trifluoromethyl)pyridin-2-yl]-6-{[2-(trifluoromethyl)pyridin-4-yl]amino}-1,3,5-triazin-2-yl)amino]propan-2-ol Methanesulfonate, 2-Propanol, 2-Methyl-1-((4-(6-(trifluoromethyl)-2-pyridinyl)-6-((2-(trifluoromethyl)-4-pyridinyl)amino)-1,3,5-triazin-2-yl)amino)-, Methanesulfonate (1:1), AG-221 Mesylate, CC-90007Given IV	Drug	Chapter 5 (glasdegib, enasidenib)
Gilteritinib FumarateAlso: ASP-2215 Hemifumarate, ASP2215 Hemifumarate, Gilteritinib Hemifumarate, XospataGiven PO	Drug	Chapter 2 (glasdegib, gilteritinib)
Glasdegib MaleateAlso: Daurismo, PF 04449913 MaleateGiven PO	Drug	Chapter 1 (glasdegib, decitabine, venetoclax), Chapter 2 (glasdegib, gilteritinib), Chapter 3 (glasdegib, bosutinib), Chapter 4 (glasdegib, ivosidenib), Chapter 5 (glasdegib, enasidenib)
IvosidenibAlso: AG-120, TibsovoGiven PO	Drug	Chapter 4 (glasdegib, ivosidenib)
VenetoclaxAlso: ABT-0199, ABT-199, ABT199, GDC-0199Given PO	Drug	Chapter 1 (glasdegib, decitabine, venetoclax)

Primary outcome

Ability to obtain a molecular diagnosis (Molecular Diagnosis Segment)
Time frame: From study enrollment to return of Molecular Diagnosis Report, assessed up to 30 days
Outcome will be dichotomized based on return in =< 10 calendar days (Yes/No). Assessed by the proportion of successful participants.
Ability to make a treatment arm assignment by the Treatment Assignment Committee (TAC) (Molecular Diagnosis Segment)
Time frame: From enrollment to treatment arm assignment by the TAC, assessed up to 30 days
Outcome will be dichotomized based on return in =< 14 calendar days (Yes/No). Assessed by the proportion of participants who receive treatment assignment from TAC.
Incidence of adverse events (Treatment Segment)
Time frame: Up to 30 days
Toxicity will be graded according to the National Cancer Institute (NCI)-Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Safety will be based on the assessment of dose limiting toxicity during cycle 1 and cycle 2. Observed toxicities will be summarized in terms of type (organ affected or laboratory determination), severity, time of onset, duration, probable association with the study treatment and reversibility or outcome.

5 secondary outcomes

Proportion of patients with successful sequencing (Molecular Diagnosis Segment)
Time frame: Up to 30 days
Proportion of patients with successful treatment arm registration (Molecular Diagnosis Segment)
Time frame: Up to 30 days
Incidence of adverse events (Molecular Diagnosis Segment)
Time frame: Up to 30 days
Overall response (Treatment Segment)
Time frame: Up to the date of the first of 2 successive bone marrows showing said response, assessed up to 30 days
Duration of remission (Treatment Segment)
Time frame: Time from the first of two consecutive bone marrow aspirates showing CR or CRi until such time as the bone marrow or peripheral blood mononuclear cells shows signs of relapse, assessed up to 30 days

Results and safety

The study was withdrawn before enrolling participants, so there are no results.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 9 Jun 2022.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Guido Marcucci principal investigator

City of Hope Medical Center

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Bosutinib Monohydrate, Decitabine and Enasidenib Mesylate in people with Recurrent Acute Myeloid Leukemia, run by City of Hope Medical Center 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 91 inclusion and 0 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: withdrawn, as of the sponsor's last update on 9 Jun 2022. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

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

Are results available for this study?

The study was withdrawn before enrolling participants, so there are no results.

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?

Ability to obtain a molecular diagnosis (Molecular Diagnosis Segment) (time frame: From study enrollment to return of Molecular Diagnosis Report, assessed up to 30 days). The study lists 3 primary outcomes in all. 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 NCT04655391.

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 9 Jun 2022.