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

NCT04231851

Last updated date
Study Location
University of California, San Francisco
San Francisco, California, 94143, United States
Contact
1-877-827-7883

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Eligibility Criteria
condition
The disease, disorder, syndrome, illness, or injury that is being studied.
Acute Myelogenous Leukemia (AML) Due to Therapy, Acute Myeloid Leukemia With Myelodysplasia-Related Changes
Sex
Females and Males
Age
Pediatric Trials: 0-17 Years
Adult Trials: 18+ Years
18 + years
Inclusion Criteria
The factors, or reasons, that allow a person to participate in a clinical study.
Show details

- Previously untreated therapy-related AML or AML with myelodysplastic related changes as described by World Health Organization (WHO) 2016

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 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:

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 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

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, corticosteroid and hydroxyurea are permitted as initial management of hyperleukocytosis at the investigator's discretion for up to 7 days after starting study therapy. Hyperleukocytosis is defined as greater than 30k WBC. When possible, a bone marrow biopsy for screening should be performed prior to the initiation hyperleukocytosis

Exclusion Criteria
The factors, or reasons, that prevent a person from participating in a clinical study.
Show details


- 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


- 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


- For patients with prior anthracycline exposure, the cumulative life-time dose should
not exceed 386mg/m2 at the time of study entry (to convert different anthracycline to
daunorubicin-equivalent, see Appendix H for conversion factors)

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Acute Myelogenous Leukemia (AML) Due to Therapy, Acute Myeloid Leukemia With Myelodysplasia-Related ChangesCPX-351 and Glasdegib for Newly Diagnosed Acute Myelogenous Leukemia With MDS Related Changes or Therapy-related Acute Myeloid Leukemia
NCT04231851
  1. San Francisco, California
  2. La Jolla, California
  3. Orange, California
ALL GENDERS
18 Years+
years
MULTIPLE SITES
Advanced Information
Descriptive Information
Brief Title  ICMJE CPX-351 and Glasdegib for Newly Diagnosed Acute Myelogenous Leukemia With MDS Related Changes or Therapy-related Acute Myeloid Leukemia
Official Title  ICMJE 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
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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Acute Myelogenous Leukemia (AML) Due to Therapy
  • Acute Myeloid Leukemia With Myelodysplasia-Related Changes
Intervention  ICMJE
  • Drug: Glasdegib
    Given PO
    Other Name: DAURISMO?
  • Drug: CPX-351
    Given IV
    Other Names:
    • Daunorubicin and cytarabine
    • VYXEOS®
Study Arms  ICMJE Experimental: CPX-351 and Glasdegib

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

Interventions:
  • Drug: Glasdegib
  • Drug: CPX-351
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: January 14, 2020)
30
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE September 30, 2022
Estimated Primary Completion Date September 30, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Previously untreated therapy-related AML or AML with myelodysplastic related changes as described by World Health Organization (WHO) 2016

    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 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:

    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 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

    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, corticosteroid and hydroxyurea are permitted as initial management of hyperleukocytosis at the investigator's discretion for up to 7 days after starting study therapy. Hyperleukocytosis is defined as greater than 30k WBC. When possible, a bone marrow biopsy for screening should be performed prior to the initiation hyperleukocytosis

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
  • 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
  • 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
  • For patients with prior anthracycline exposure, the cumulative life-time dose should not exceed 386mg/m2 at the time of study entry (to convert different anthracycline to daunorubicin-equivalent, see Appendix H for conversion factors)
Sex/Gender  ICMJE
Sexes Eligible for Study:All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Chao Family Comprehensive Cancer Center University of California, Irvine1-877-827-7883[email protected]
Contact: University of California Irvine Medical
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04231851
Other Study ID Numbers  ICMJE UCI 18-105 [HS# 2019-5533]
2019-5533 ( Other Identifier: University of California, Irvine )
UCHMC1913 ( Other Identifier: University of California Hematologic Malignancies Consortium )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Deepa Jeyakumar, University of California, Irvine
Study Sponsor  ICMJE University of California, Irvine
Collaborators  ICMJE
  • Jazz Pharmaceuticals
  • Pfizer
Investigators  ICMJE
Principal Investigator:Deepa Jeyakumar, MDChao Family Comprehensive Cancer Center
PRS Account University of California, Irvine
Verification Date April 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP