CPX-351 and Glasdegib for Newly Diagnosed Acute Myelogenous Leukemia With MDS Related Changes or Therapy-related Acute Myeloid Leukemia

NCT04231851 | Active Not Recruiting Phase 2 Results DMC FDA Drug

• 3 other identifiers: 20195533UCI 18-105UCHMC1913
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 4

Brief Summary

This is a phase 2 single-arm, open-label clinical trial determining efficacy of CPX-351 in combination with Glasdegib in subjects with Acute Myelogenous Leukemia with myelodysplastic syndrome related changes or therapy-related acute myeloid leukemia.

Conditions

Acute Myelogenous Leukemia (AML) Due to Therapy; Acute Myeloid Leukemia With Myelodysplasia-Related Changes

Keywords

Therapy-Related AML; AML with MDS related changes

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants With Event-Free Survival at 6 Months

  This is defined as the percentage of subjects with event-free survival (EFS) at 6 months. EFS is defined as the number of months where patients are in a remission state.

  6 months

Secondary Outcomes (6)

• Percentage of Grade 3-5 Adverse Events

  From the start date of treatment until 4 weeks after removal of treatment due to disease progression, toxicity, delay of treatment, or withdrawal of treatment, whichever came first, an average of 1 year.

• Overall Response Rate

  From the start date of treatment until first date of CR/CRi or an average of 1 year.

• Durability of Response

  From the start date of treatment until first date of CR/CRi or an average of 1 year.

• Overall Survival of Patients Who Received the Combination of CPX-351 and Glasdegib

  Time from screening biopsy for up to 12 months after the last patient is enrolled or until death from any cause, whichever came first.

• Time to Normal Hematopoiesis as Assessed by Laboratory Studies

  From the start date of treatment until laboratory studies confirmation of normal hematopoiesis or an average of 1 year

Study Arms (1)

CPX-351 and Glasdegib

EXPERIMENTAL

In Induction, subjects receive 44mg/m2/100mg/m2 IV on days 1, 3 and 5 and Glasdegib 100mg PO daily on days 6 to 28. If re-induction is needed: Subjects receive 44mg/m2/100mg/m2 IV on days 1 and 3 and Glasdegib 100mg PO daily on days 4 to 28. In consolidation: Subjects receive 29mg/m2/65mg/m2 IV on days 1 and 3 and Glasdegib 100mg PO daily on days 4 to 28. If maintenance is required, Subjects receive Glasdegib 100mg PO daily for up to one year

Drug: Glasdegib; Drug: CPX-351

Interventions

Glasdegib DRUG

Given PO

Also known as: DAURISMO™

CPX-351 and Glasdegib

CPX-351 DRUG

Given IV

Also known as: Daunorubicin and cytarabine, VYXEOS®

CPX-351 and Glasdegib

Eligibility Criteria

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

You may qualify if:

• Previously untreated therapy-related AML or AML with myelodysplastic related changes as described by World Health Organization (WHO) 2016
• AML arising in MDS (including CMML) or MDS/MPN syndrome
• AML with MDS-related cytogenetic abnormalities (Appendix A, metaphase FISH allowable as surrogate for cytogenetics)
• AML with multi-lineage dysplasia involving the presence of 50% or more dysplastic cells in at least two cell lines and in the absence of mutation in NPM1 or biallelic CEBPA (as per WHO 2016)
• Adults 18 years of age or older
• ECOG performance status 0 to 2
• Adequate organ function as defined as:
• Left Ventricular Ejection Fraction (LVEF) \> 50%
• Serum total bilirubin \< 2.0 mg/dL, unless considered due to Gilbert's disease or leukemic involvement
• AST, ALT and alkaline phosphatase \< 3 times the upper limit of normal, unless considered due to leukemic involvement
• Serum creatinine \< 2.0 mg/dL, or creatinine clearance \> 40 mL/min based on Cockcroft-Gault GFR
• Absence of unstable cardiac disease defined as myocardial infarction within 6 months, uncontrolled heart failure, or uncontrolled cardiac arrhythmia
• Ability to understand and the willingness to sign a written informed consent or subject's legally authorize representative (LAR) has provided informed consent prior to any study-specific activities/procedures being initiated when the subject has any kind of condition that, in the opinion of the investigator, may compromise the ability of the subject to give written informed consent
• Women of child-bearing potential and men with partners of child-bearing potential must agree to use 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study through 120 days after the last dose of study medication
• A woman of child-bearing potential is any female (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria:

You may not qualify if:

• Prior treatment with Glasdegib or CPX-351
• Previously treated AML except for initial management of hyperleukocytosis. Treatment with hypomethylating therapy for MDS is allowable but not since their diagnosis of AML. No prior treatment with cytarabine or daunorubicin are allowed
• Concurrent FLT3 mutation that the treating physician deems necessary to treat with midostaurin, whereas patients with FLT3-mutated AML not treated with midostaurin can be enrolled. Patients with known Core Binding Factor -t(8;21), inv(16), t(16;16) are allowed for study participation at the treating investigator's discretion
• Active CNS or testicular involvement by leukemia; diagnostic lumbar puncture is not required
• History of neurologic disorder including but not limited to: prior seizure, epilepsy, structural brain abnormality, benign brain tumor, stroke, brain injuries, dementia, movement disorder or other significant CNS abnormalities
• Baseline QT corrected interval based on Fridericia's formula (QTcF) interval \> 450 ms
• Acute coronary syndrome in the past 12 months, NYHA class III or VI
• Known history of Wilson's disease or other copper handling disorder
• History of GI malabsorptive disease
• Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or in situ cervical cancer that has undergone potentially curative therapy
• Known HIV infection
• Active hepatitis B or hepatitis C infection (patients who successfully completed curative hepatitis C therapy can be enrolled)
• Any uncontrolled infection, active bacterial or viral infection manifesting as fevers or hemodynamic instability within the past 72 hours
• Proven active invasive fungal infection
• Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment

Sponsors & Collaborators

• Pfizer: collaborator
• University of California, Irvine: lead
• Jazz Pharmaceuticals: collaborator

Study Sites (4)

University of California, Los Angeles

Los Angeles, California, 90095, United States

Location

Chao Family Comprehensive Cancer Center, University of California, Irvine

Orange, California, 92868, United States

Location

University of California, Davis

Sacramento, California, 95817, United States

Location

University of California, San Francisco

San Francisco, California, 94143, United States

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

glasdegib; CPX-351; Daunorubicin; Cytarabine

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Results Point of Contact

• Title: Chao Family Comprehensive Cancer Center, University of California, Irvine
• Organization: Chao Family Comprehensive Cancer Center, University of California, Irvine

ucstudy@uci.edu

1-877-UC-STUDY

Study Officials

• Deepa Jeyakumar, MD

  Chao Family Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: HS Associate Clinical Professor

Study Record Dates

• First Submitted: January 14, 2020
• First Posted: January 18, 2020
• Study Start: February 19, 2020
• Primary Completion: June 30, 2024
• Study Completion (Estimated): June 30, 2027
• Last Updated: March 6, 2026
• Results First Posted: March 6, 2026

Record last verified: 2025-10

Locations

US (4)