Clinical Trials /

A Phase 1b Master Trial to Investigate CPX-351 in Subjects With Previously Untreated Acute Myeloid Leukemia

NCT04075747

Description:

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.

Related Conditions:
  • Acute Myeloid Leukemia
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: A Phase 1b Master Trial to Investigate CPX-351 in Subjects With Previously Untreated Acute Myeloid Leukemia
  • Official Title: V-FAST: A Phase 1b Master Trial to Investigate CPX-351 Combined With Various Targeted Agents in Subjects With Previously Untreated Acute Myeloid Leukemia

Clinical Trial IDs

  • ORG STUDY ID: JZP025-101
  • NCT ID: NCT04075747

Conditions

  • Acute Myeloid Leukemia

Interventions

DrugSynonymsArms
CPX-351VyxeosArm A
VenetoclaxVenclextaArm A
MidostaurinRydaptArm B
EnasidenibIdhifaArm C

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.

Trial Arms

NameTypeDescriptionInterventions
Arm AExperimental
  • CPX-351
  • Venetoclax
Arm BExperimental
  • CPX-351
  • Midostaurin
Arm CExperimental
  • CPX-351
  • Enasidenib

Eligibility Criteria

        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.
      
Maximum Eligible Age:75 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Determine the Recommended Phase 2 Dose (RP2D)
Time Frame:Up to 30 months
Safety Issue:
Description:The RP2D will be determined by the specified dose de-escalation/dose escalation algorithm.

Secondary Outcome Measures

Measure:Proportion of subjects who have achieved CR, CRi, CRh, CR + CRi, and CR + CRh
Time Frame:Up to 30 months
Safety Issue:
Description:After up to 2 inductions
Measure:Proportion of subjects who have achieved CR / CRi with MRD negative status
Time Frame:Up to 30 months
Safety Issue:
Description:After up to 2 inductions
Measure:Proportion of subjects who have achieved CR / CRh with MRD negative status
Time Frame:Up to 30 months
Safety Issue:
Description:After up to 2 inductions

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Jazz Pharmaceuticals

Last Updated

November 19, 2019