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

NCT04655391 | Withdrawn Phase 1 DMC FDA Drug

• 3 other identifiers: 20456NCI-2020-10595P30CA033572
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Recurrent Acute Myeloid Leukemia

Outcome Measures

Primary Outcomes (3)

• 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.

  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.

  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.

  Up to 30 days

Secondary Outcomes (5)

• Proportion of patients with successful sequencing (Molecular Diagnosis Segment)

  Up to 30 days

• Proportion of patients with successful treatment arm registration (Molecular Diagnosis Segment)

  Up to 30 days

• Incidence of adverse events (Molecular Diagnosis Segment)

  Up to 30 days

• Overall response (Treatment Segment)

  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 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

Other Outcomes (1)

• Change in leukemia stem cell (LSC) burden (Treatment Segment)

  Baseline up to post-treatment (2 cycles) (each cycle = 28 days)

Study Arms (5)

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.

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.

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.

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.

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.

Drug: Enasidenib Mesylate; Drug: Glasdegib Maleate

Interventions

Bosutinib Monohydrate DRUG

Given PO

Also known as: 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 DRUG

Given IV

Also known as: 5-Aza-2''-deoxycytidine, Dacogen, Decitabine for Injection, Deoxyazacytidine, Dezocitidine

Chapter 1 (glasdegib, decitabine, venetoclax)

Enasidenib Mesylate DRUG

Given IV

Also known as: 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 DRUG

Given PO

Also known as: ASP-2215 Hemifumarate, ASP2215 Hemifumarate, Gilteritinib Hemifumarate, Xospata

Chapter 2 (glasdegib, gilteritinib)

Glasdegib Maleate DRUG

Given PO

Also known as: Daurismo, PF 04449913 Maleate

Chapter 1 (glasdegib, decitabine, venetoclax); Chapter 2 (glasdegib, gilteritinib); Chapter 3 (glasdegib, bosutinib); Chapter 4 (glasdegib, ivosidenib); Chapter 5 (glasdegib, enasidenib)

Ivosidenib DRUG

Given PO

Also known as: AG-120, Tibsovo

Chapter 4 (glasdegib, ivosidenib)

Venetoclax DRUG

Given PO

Also known as: ABT-0199, ABT-199, ABT199, GDC-0199, RG7601, Venclexta, Venclyxto

Chapter 1 (glasdegib, decitabine, venetoclax)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

Sponsors & Collaborators

• City of Hope Medical Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

City of Hope Meidcal Center

Duarte, California, 91010, United States

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

bosutinib; Decitabine; Injections; 2-Propanol; methanesulfonic acid; enasidenib; gilteritinib; glasdegib; ivosidenib; venetoclax

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Azacitidine; Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides; Drug Administration Routes; Drug Therapy; Therapeutics; Propanols; Alcohols

Study Officials

• Guido Marcucci

  City of Hope Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 23, 2020
• First Posted: December 7, 2020
• Study Start: June 25, 2022
• Primary Completion: December 15, 2023
• Study Completion: December 15, 2023
• Last Updated: June 9, 2022

Record last verified: 2022-06

Locations

US (1)