Purpose

JZP025-101 is an open-label, multicenter, multi-arm, nonrandomized phase 1b master trial to determine the recommended phase 2 dose (RP2D) of CPX-351 when administered in combination with various targeted agents in previously untreated subjects with Acute Myeloid Leukemia (AML) who are fit to receive intensive chemotherapy (ICT). Subjects will be assigned to treatment arms based on results of AML mutation testing.

Condition

Eligibility

Eligible Ages
Between 18 Years and 75 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

Inclusion Criteria

  • Age ≥ 18 to ≤ 75 years at the time of informed consent. - Newly diagnosed AML according to World Health Organization (WHO) pathological criteria (with at least 20% blasts in the peripheral blood or bone marrow). - ECOG performance status of 0 to 2. - Laboratory values fulfilling the following: - Serum creatinine < 2.0 mg/dL. - Serum total bilirubin < 2.0 mg/dL. (For subjects with Gilbert's Syndrome and serum total bilirubin ≥ 2.0 mg/dL, the medical monitor should be contacted.) - Serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST) < 3 times the upper limit of normal (ULN). (Note: If elevated liver enzymes > ULN are related to disease, contact medical monitor to discuss.) - Cardiac ejection fraction ≥ 50% by echocardiography or multiple gated acquisition scan (MUGA). - Subjects with second malignancies in remission may be eligible if there is clinical evidence of disease stability for a period > 6 months off cytotoxic chemotherapy, documented by imaging, tumor marker studies, etc., at screening. Subjects maintained on long-term nonchemotherapy treatment (eg, hormonal therapy) are eligible.

Exclusion Criteria

  • Acute promyelocytic leukemia [t(15;17)]. - Subject has favorable risk cytogenetics ((t8;21), inv(16), t(16;16), or t15;17) karyotype abnormalities) as categorized by the National Comprehensive Cancer Network (NCCN) Guidelines Version 2.2014 for AML (NCCN 2014). - Clinical evidence of active central nervous system (CNS) leukemia. - Subjects with active (uncontrolled, metastatic) second malignancies. - Subjects who have received prior treatment intended for induction therapy of AML; only hydroxyurea is permitted for control of blood cell counts. (For example, a subject with myelodysplastic syndrome [MDS] who changes hypomethylating agent [HMA] dose and schedule after the diagnosis of AML is excluded. AML-type therapy, such as cytarabine alone [> 1g/m2/day] or cytarabine plus an anthracycline as well as prior HSCT are also excluded.) - Subjects receiving administration of any therapy for MDS (conventional or investigational) must be completed by 2 weeks prior to the first dose of study drug. In the event of rapidly proliferative disease, use of hydroxyurea is permitted until 24 hours before the start of study treatment. Toxicities associated with prior MDS therapy must have recovered to Grade 1 or less prior to start of treatment. - Subjects with myocardial impairment of any cause (eg, cardiomyopathy, ischemic heart disease, significant valvular dysfunction, hypertensive heart disease, and congestive heart failure) resulting in heart failure by New York Heart Association Criteria (Class III or IV staging). - Subjects with active or uncontrolled infection. Subjects with an infection receiving treatment (antibiotic, antifungal or antiviral treatment) may be entered into the study but must be afebrile and hemodynamically stable for ≥ 72 hours. - Current evidence of invasive fungal infection (blood or tissue culture). Subjects with recent fungal infection must have a subsequent negative culture to be eligible. - Subjects with known human immunodeficiency virus (new testing not required) or evidence of active hepatitis B or C infection. - Subjects with known history of Wilson's disease or other known copper-metabolism disorder. - Subjects with other comorbidity that the investigator judges to be incompatible with conventional ICT, and / or the targeted agent.

Study Design

Phase
Phase 1
Study Type
Interventional
Allocation
Non-Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Arm A
  • Drug: CPX-351
    Up to 2 induction and 2 consolidation courses will be offered
    Other names:
    • Vyxeos
  • Drug: Venetoclax
    Will be administered over specified duration during induction and consolidation courses
    Other names:
    • Venclexta
Experimental
Arm B
  • Drug: CPX-351
    Up to 2 induction and 2 consolidation courses will be offered
    Other names:
    • Vyxeos
  • Drug: Midostaurin
    Will be administered over specified duration during induction and consolidation courses
    Other names:
    • Rydapt
Experimental
Arm C
  • Drug: CPX-351
    Up to 2 induction and 2 consolidation courses will be offered
    Other names:
    • Vyxeos
  • Drug: Enasidenib
    Will be administered over specified duration during induction and consolidation courses
    Other names:
    • Idhifa

Recruiting Locations

University of Kansas Cancer Center
Fairway, Kansas 66205

More Details

Status
Recruiting
Sponsor
Jazz Pharmaceuticals

Study Contact

Director Clinical Trial Disclosure & Transparency
2159707145
ClinicalTrialDisclosure@JazzPharma.com

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.