Summary

Eligibility
for people ages 18 years and up (full criteria)
Location
at Orange, California
Dates
study started
estimated completion
Principal Investigator
Deepa Jeyakumar

Description

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.

Official Title

Phase II Study of the Combination of CPX-351 and Glasdegib in Previously Untreated Patients With Acute Myelogenous Leukemia With MDS Related Changes or Therapy-related Acute Myeloid Leukemia

Keywords

Acute Myelogenous Leukemia (AML) Due to Therapy Acute Myeloid Leukemia With Myelodysplasia-Related Changes Therapy-Related AML AML with MDS related changes Leukemia Leukemia, Myeloid Leukemia, Myeloid, Acute Preleukemia Myelodysplastic Syndromes Cytarabine Daunorubicin Glasdegib CPX-351 CPX-351 and Glasdegib

Eligibility

You can join if…

Open to people ages 18 years and up

  • Previously untreated therapy-related AML or AML with myelodysplastic related changes as described by World Health Organization (WHO)
  • 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 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
  • 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:
  • Has not undergone a hysterectomy or bilateral oophorectomy; or
  • Has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months)
  • Women of child-bearing potential has negative pregnancy test within 72 hours of initiating study drug dosing
  • Male subjects must agree to use a latex condom during sexual contact with females of childbearing potential even if they have had a successful vasectomy starting with the first dose of study therapy through 120 days after the last dose of study therapy
  • Leukapheresis, corticosteroids and hydroxyurea are permitted after screening bone marrow biopsy is performed for up to 7 days prior to starting study therapy as management of hyperleukocytosis at the investigator's discretion. Hyperleukocytosis is defined as greater than 30k WBC

You CAN'T join 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
  • Exclude patients with prior history of MPN including PV, ET, Myelofibrosis, or CML that has now evolved into AML
  • Active CNS or testicular involvement by leukemia
  • 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
  • Severe or uncontrolled medical disorder that would, in the investigator's opinion, impair ability to receive study treatment (i.e., uncontrolled diabetes, chronic renal disease, chronic pulmonary disease or active, uncontrolled infection, psychiatric illness/social situations that would limit compliance with study requirements
  • Current or anticipated use of other investigational agents

Location

  • Chao Family Comprehensive Cancer Center, University of California, Irvine
    Orange California 92868 United States

Lead Scientist at UC Irvine

  • Deepa Jeyakumar
    Associate Clinical Professor, Medicine. Authored (or co-authored) 7 research publications.

Details

Status
not yet accepting patients
Start Date
Completion Date
(estimated)
Sponsor
University of California, Irvine
ID
NCT04231851
Phase
Phase 2
Study Type
Interventional
Last Updated