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

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

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.

Study Overview

• Status: Completed
• Conditions: Acute Myeloid Leukemia
• Intervention / Treatment: Drug: CPX-351; Drug: Venetoclax; Drug: Midostaurin; Drug: Enasidenib

• Study Type: Interventional
• Enrollment (Actual): 57
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Duarte, California, United States, 91010
      • City of Hope National Medical Center
    • Palo Alto, California, United States, 94305
      • Stanford University School of Medicine- Standford Cancer Institute
  • Georgia
    • Augusta, Georgia, United States, 30912
      • Georgia Cancer Center at Augusta University
  • Kansas
    • Fairway, Kansas, United States, 66205
      • University of Kansas Cancer Center
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Johns Hopkins University
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
  • Nebraska
    • Omaha, Nebraska, United States, 68105
      • University of Nebraska Medical Center
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
      • Hackensack University Medical Center
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt Ingram Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.) All-trans-retinoic acid (ATRA) used empirically is permitted.
• 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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm A	Drug: CPX-351; Up to 2 induction and 2 consolidation courses will be offered; Other Names: Vyxeos; JZP351; 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; JZP351; 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; JZP351; Drug: Enasidenib; Will be administered over specified duration during induction and consolidation courses; Other Names: Idhifa

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Determine the Recommended Phase 2 Dose (RP2D)	The RP2D will be determined by the specified dose de-escalation/dose escalation algorithm.	Up to 30 months
Safety and Tolerability of CPX-351 and Targeted Agents: incidence of adverse events (AEs) and dose limiting toxicities (DLTs)	The safety and tolerability of CPX-351 and targeted agents when given in combination, based on the incidence of adverse events (AEs) and dose limiting toxicities (DLTs)	Up to 30 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of subjects who have achieved CR, CRi, CRh, CR + CRi, CR + CRh, and morphologic leukemia-free state (MLFS)	After up to 2 inductions	Up to 30 months
Proportion of subjects who have achieved CR / CRi with MRD negative status	After up to 2 inductions	Up to 30 months
Proportion of subjects who have achieved CR / CRh with MRD negative status	After up to 2 inductions	Up to 30 months

Collaborators and Investigators

• Sponsor: Jazz Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): December 2, 2019
• Primary Completion (Actual): February 7, 2022
• Study Completion (Actual): September 12, 2023

Study Registration Dates

• First Submitted: August 29, 2019
• First Submitted That Met QC Criteria: August 30, 2019
• First Posted (Actual): September 3, 2019

Study Record Updates

• Last Update Posted (Actual): October 16, 2023
• Last Update Submitted That Met QC Criteria: October 12, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Venetoclax; Midostaurin
• Other Study ID Numbers: JZP025-101

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No