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

NCT04075747 | Completed Phase 1 FDA Drug

• 1 other identifier: JZP025-101
• Study Type: interventional
• Target: 57
• Locations: 1 country
• Sites: 10

Brief Summary

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.

Conditions

Acute Myeloid Leukemia

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (3)

• Proportion of subjects who have achieved CR, CRi, CRh, CR + CRi, CR + CRh, and morphologic leukemia-free state (MLFS)

  Up to 30 months

• Proportion of subjects who have achieved CR / CRi with MRD negative status

  Up to 30 months

• Proportion of subjects who have achieved CR / CRh with MRD negative status

  Up to 30 months

Study Arms (3)

Arm A

EXPERIMENTAL

Drug: CPX-351; Drug: Venetoclax

Arm B

EXPERIMENTAL

Drug: CPX-351; Drug: Midostaurin

Arm C

EXPERIMENTAL

Drug: CPX-351; Drug: Enasidenib

Interventions

CPX-351 DRUG

Up to 2 induction and 2 consolidation courses will be offered

Also known as: Vyxeos, JZP351

Arm A; Arm B; Arm C

Venetoclax DRUG

Will be administered over specified duration during induction and consolidation courses

Also known as: Venclexta

Arm A

Midostaurin DRUG

Will be administered over specified duration during induction and consolidation courses

Also known as: Rydapt

Arm B

Enasidenib DRUG

Will be administered over specified duration during induction and consolidation courses

Also known as: Idhifa

Arm C

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Jazz Pharmaceuticals: lead

Study Sites (10)

City of Hope National Medical Center

Duarte, California, 91010, United States

Location

Stanford University School of Medicine- Standford Cancer Institute

Palo Alto, California, 94305, United States

Location

Georgia Cancer Center at Augusta University

Augusta, Georgia, 30912, United States

Location

University of Kansas Cancer Center

Fairway, Kansas, 66205, United States

Location

Johns Hopkins University

Baltimore, Maryland, 21287, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

University of Nebraska Medical Center

Omaha, Nebraska, 68105, United States

Location

Hackensack University Medical Center

Hackensack, New Jersey, 07601, United States

Location

Duke University

Durham, North Carolina, 27710, United States

Location

Vanderbilt Ingram Cancer Center

Nashville, Tennessee, 37232, United States

Location

Related Publications (1)

• Pullarkat VA, Levis M, McCloskey J, Mannis GN, Strickland SA, Fathi AT, Lin TL, Bhatt VR, Vanniyasingam T, Chakravarthy D, Lutska Y, Faderl S, Cheung RS, Erba HP. V-FAST: a phase 1b master trial to investigate CPX-351 combined with targeted agents in adults with newly diagnosed AML. Blood Neoplasia. 2025 Jun 3;2(4):100123. doi: 10.1016/j.bneo.2025.100123. eCollection 2025 Nov.

  PMID: 40932876 DERIVED

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

CPX-351; venetoclax; midostaurin; enasidenib

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 29, 2019
• First Posted: September 3, 2019
• Study Start: December 2, 2019
• Primary Completion: February 7, 2022
• Study Completion: September 12, 2023
• Last Updated: October 16, 2023

Record last verified: 2023-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (10)