Clinical Trials /

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

NCT04231851

Description:

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.

Related Conditions:
  • Secondary Acute Myeloid Leukemia
  • Therapy-Related Acute Myeloid Leukemia
Recruiting Status:

Not yet recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: CPX-351 and Glasdegib for Newly Diagnosed Acute Myelogenous Leukemia With MDS 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

Clinical Trial IDs

  • ORG STUDY ID: UCI 18-105
  • SECONDARY ID: 2019-5533
  • SECONDARY ID: UCHMC1913
  • NCT ID: NCT04231851

Conditions

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

Interventions

DrugSynonymsArms
GlasdegibDAURISMO™CPX-351 and Glasdegib
CPX-351Daunorubicin and cytarabine, VYXEOS®CPX-351 and Glasdegib

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
CPX-351 and GlasdegibExperimentalIn 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 29mg/m2/65mg/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
  • Glasdegib
  • CPX-351

Eligibility Criteria

        Inclusion Criteria:

          -  Previously untreated therapy-related AML or AML with myelodysplastic related changes
             as described by World Health Organization (WHO)

               1. AML arising in MDS (including CMML) or MDS/MPN syndrome

               2. AML with MDS-related cytogenetic abnormalities (Appendix A, metaphase FISH
                  allowable as surrogate for cytogenetics)

               3. 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:

               1. Left Ventricular Ejection Fraction (LVEF) > 50%

               2. Serum total bilirubin < 2.0 mg/dL, unless considered due to Gilbert's disease or
                  leukemic involvement

               3. AST, ALT and alkaline phosphatase < 3 times the upper limit of normal, unless
                  considered due to leukemic involvement

               4. 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

               1. 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:

                    1. Has not undergone a hysterectomy or bilateral oophorectomy; or

                    2. 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)

               2. Women of child-bearing potential has negative pregnancy test within 72 hours of
                  initiating study drug dosing

               3. 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

        Exclusion Criteria:

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

Primary Outcome Measures

Measure:Percentage of Participants with Event-Free Survival at 6 months
Time Frame:6 months
Safety Issue:
Description: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.

Secondary Outcome Measures

Measure:Percentage of Grade 3-5 Adverse Events
Time Frame: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.
Safety Issue:
Description:To evaluate the tolerability of administering CPX-351 in combination with glasdegib in patients with newly diagnosed with Acute Myeloid Leukemia (AML) with Myelodysplastic Syndrome (MDS) related changes or treatment-related AML from the start of treatment, duration of treatment and up to 4 weeks after completion of study treatment. Toxicity and adverse events are based on the CTCAE (NCI Common Terminology Criteria for Adverse Events) Version 5.0.
Measure:Overall Response Rate
Time Frame:From the start date of treatment until first date of CR/CRi or an average of 1 year.
Safety Issue:
Description:To assess the overall response rate to the combination of CPX-351 and glasdegib. The overall response rate (ORR) is defined as the rate of complete remissions (CR) and complete remission with incomplete count recovery (CRi). ORR = CR + CRi
Measure:Durability of Response
Time Frame:From the start date of treatment until first date of CR/CRi or an average of 1 year.
Safety Issue:
Description:Durability of response is measured by relapse-free survival (RFS). RFS is defined as the amount of time a patient remains in remission after having achieved a CR or CRi
Measure:Overall Survival of Patients who received the combination of CPX-351 and glasdegib
Time Frame:Time from screening biopsy for up to 12 months after the last patient is enrolled or until death from any cause, whichever came first.
Safety Issue:
Description:To evaluate the overall survival of patients with newly diagnosed with Acute Myeloid Leukemia (AML) with Myelodysplastic Syndrome (MDS) related changes or treatment-related AML.
Measure:Time to normal hematopoiesis as assessed by laboratory studies
Time Frame:From the start date of treatment until laboratory studies confirmation of normal hematopoiesis or an average of 1 year
Safety Issue:
Description:To evaluate the time to normal hematopoiesis, process by which blood cells are formed, as determined by laboratory studies inclusive of complete blood counts (CBCs)
Measure:Number of participants who go on to receive an allogenic hematopoietic stem cell transplant
Time Frame:Up to 3 years
Safety Issue:
Description:This is defined as the number of participants who continue on to receive an allogenic hematopoietic stem cell transplant after induction, re-induction, or consolidation.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:University of California, Irvine

Trial Keywords

  • Therapy-Related AML
  • AML with MDS related changes

Last Updated

January 14, 2020