Clinical Trial: NCT04655391 - My Cancer Genome

NCT04655391

Description:

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 Conditions:

Acute Myeloid Leukemia
Acute Promyelocytic Leukemia

Recruiting Status:

Not yet recruiting

Phase:

Phase 1

URL:

https://clinicaltrials.gov/show/NCT04655391

Trial Eligibility

Document

Title

Brief Title: Glasdegib-Based Treatment Combinations for the Treatment of Patients With Relapsed Acute Myeloid Leukemia Who Have Undergone Hematopoietic Cell Transplantation
Official Title: A Pilot/Phase 1b Study of Glasdegib-Based Treatment Combinations in Adult Patients With Relapsed AML Post Allogeneic Hematopoietic Cell Transplantation

Clinical Trial IDs

ORG STUDY ID: 20456
SECONDARY ID: NCI-2020-10595
SECONDARY ID: 20456
SECONDARY ID: P30CA033572
NCT ID: NCT04655391

Conditions

Recurrent Acute Myeloid Leukemia

Interventions

Drug	Synonyms	Arms
Bosutinib Monohydrate	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	Chapter 3 (glasdegib, bosutinib)
Decitabine	5-Aza-2''-deoxycytidine, Dacogen, Decitabine for Injection, Deoxyazacytidine, Dezocitidine	Chapter 1 (glasdegib, decitabine, venetoclax)
Enasidenib Mesylate	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	Chapter 5 (glasdegib, enasidenib)
Gilteritinib Fumarate	ASP-2215 Hemifumarate, ASP2215 Hemifumarate, Gilteritinib Hemifumarate, Xospata	Chapter 2 (glasdegib, gilteritinib)
Glasdegib Maleate	Daurismo, PF 04449913 Maleate	Chapter 1 (glasdegib, decitabine, venetoclax)
Ivosidenib	AG-120, Tibsovo	Chapter 4 (glasdegib, ivosidenib)
Venetoclax	ABT-0199, ABT-199, ABT199, GDC-0199, RG7601, Venclexta, Venclyxto	Chapter 1 (glasdegib, decitabine, venetoclax)

Purpose

Detailed Description

      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.

Trial Arms

Name	Type	Description	Interventions
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.	Decitabine Glasdegib Maleate 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.	Gilteritinib Fumarate 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.	Bosutinib Monohydrate 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.	Glasdegib Maleate 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.	Enasidenib Mesylate Glasdegib Maleate

Eligibility Criteria

        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

Maximum Eligible Age:	N/A
Minimum Eligible Age:	18 Years
Eligible Gender:	All
Healthy Volunteers:	No

Primary Outcome Measures

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
Safety Issue:
Description:	Outcome will be dichotomized based on return in =< 10 calendar days (Yes/No). Assessed by the proportion of successful participants.

Secondary Outcome Measures

Measure:	Proportion of patients with successful sequencing (Molecular Diagnosis Segment)
Time Frame:	Up to 30 days
Safety Issue:
Description:	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.

Measure:	Proportion of patients with successful treatment arm registration (Molecular Diagnosis Segment)
Time Frame:	Up to 30 days
Safety Issue:
Description:	Successful placement defined as the enrollment of a participant into one of the treatment arms.

Measure:	Incidence of adverse events (Molecular Diagnosis Segment)
Time Frame:	Up to 30 days
Safety Issue:
Description:	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.

Measure:	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
Safety Issue:
Description:	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).

Measure:	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
Safety Issue:
Description:

Details

Phase:	Phase 1
Primary Purpose:	Interventional
Overall Status:	Not yet recruiting
Lead Sponsor:	City of Hope Medical Center

Last Updated

August 12, 2021

Clinical Trials /

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