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

Summary

Participation Requirements

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 stud...

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.

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