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

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

WITHDRAWN

Clinical Phase

PHASE1

Study Classification

INTERVENTIONAL

Study Start Date

2022-06-25

Study Completion Date

2023-12-15

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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.

Related Clinical Trials

Explore similar clinical trials based on study characteristics and research focus.

Demethylating Agents Combined With Venetoclax for High-risk T-cell Lymphoblastic Lymphoma/Leukemia Post-Transplant Relapse Prevention

NCT06686108

T-cell Acute Lymphoblastic Leukemia ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION Relapse

RECRUITING PHASE2

A Study Evaluating Intensive Chemotherapy With or Without Glasdegib or Azacitidine With or Without Glasdegib In Patients With Previously Untreated Acute Myeloid Leukemia

NCT03416179

Leukemia, Myeloid, Acute

COMPLETED PHASE3

Decitabine With GCLAM for Adults With Newly Diagnosed, Relapsed, or Refractory AML or High-Risk MDS

NCT02921061

Mixed Phenotype Acute Leukemia Previously Treated Myelodysplastic Syndrome Recurrent Adult Acute Myeloid Leukemia +4 more

COMPLETED PHASE1/PHASE2

Decitabine, Donor Natural Killer Cells, and Aldesleukin in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia

NCT02316964

Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities Adult Acute Myeloid Leukemia With Del(5q) Adult Acute Myeloid Leukemia With Inv(16)(p13;q22) +5 more

COMPLETED PHASE1

Decitabine and Venetoclax Treatment as Maintenance Therapy in Patients Post Allograft Stem Cell Transplant

NCT06129734

Myeloid Malignancy Acute Myeloid Leukemia

RECRUITING PHASE1/PHASE2

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

PRIMARY OBJECTIVES:

I. 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:

I. 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:

I. 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

See the medical conditions and disease areas that this research is targeting or investigating.

Recurrent Acute Myeloid Leukemia

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Intervention Type DRUG

Given PO

Discover alternative or legacy names that may be used to describe the listed interventions across different sources.

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 5-Aza-2''-deoxycytidine Dacogen Decitabine for Injection Deoxyazacytidine Dezocitidine 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 Enasidenib Methanesulfonate Idhifa ASP-2215 Hemifumarate ASP2215 Hemifumarate Gilteritinib Hemifumarate Xospata Daurismo PF 04449913 Maleate AG-120 Tibsovo ABT-0199 ABT-199 ABT199 GDC-0199 RG7601 Venclexta Venclyxto

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

* 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
* 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

Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No