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

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ClinicalTrials.gov Identifier: NCT04075747
Recruitment Status : Not yet recruiting
First Posted : September 2, 2019
Last Update Posted : September 2, 2019
Sponsor:
Information provided by (Responsible Party):
Jazz Pharmaceuticals

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.

Condition or disease Intervention/treatment Phase
Acute Myeloid Leukemia Drug: CPX-351 Drug: Venetoclax Drug: Midostaurin Drug: Enasidenib Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 96 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Estimated Study Start Date : October 2019
Estimated Primary Completion Date : April 2022
Estimated Study Completion Date : April 2022


Arm Intervention/treatment
Experimental: Arm A Drug: CPX-351
Up to 2 induction and 2 consolidation courses will be offered
Other Name: Vyxeos

Drug: Venetoclax
Will be administered over specified duration during induction and consolidation courses
Other Name: Venclexta

Experimental: Arm B Drug: CPX-351
Up to 2 induction and 2 consolidation courses will be offered
Other Name: Vyxeos

Drug: Midostaurin
Will be administered over specified duration during induction and consolidation courses
Other Name: Rydapt

Experimental: Arm C Drug: CPX-351
Up to 2 induction and 2 consolidation courses will be offered
Other Name: Vyxeos

Drug: Enasidenib
Will be administered over specified duration during induction and consolidation courses
Other Name: Idhifa




Primary Outcome Measures :
  1. Determine the Recommended Phase 2 Dose (RP2D) [ Time Frame: Up to 30 months ]
    The RP2D will be determined by the specified dose de-escalation/dose escalation algorithm.

  2. Safety and Tolerability of CPX-351 and Targeted Agents: incidence of adverse events (AEs) and dose limiting toxicities (DLTs) [ Time Frame: Up to 30 months ]
    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)


Secondary Outcome Measures :
  1. Proportion of subjects who have achieved CR, CRi, CRh, CR + CRi, and CR + CRh [ Time Frame: Up to 30 months ]
    After up to 2 inductions

  2. Proportion of subjects who have achieved CR / CRi with MRD negative status [ Time Frame: Up to 30 months ]
    After up to 2 inductions

  3. Proportion of subjects who have achieved CR / CRh with MRD negative status [ Time Frame: Up to 30 months ]
    After up to 2 inductions



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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04075747


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

Sponsors and Collaborators
Jazz Pharmaceuticals

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Responsible Party: Jazz Pharmaceuticals
ClinicalTrials.gov Identifier: NCT04075747     History of Changes
Other Study ID Numbers: JZP025-101
First Posted: September 2, 2019    Key Record Dates
Last Update Posted: September 2, 2019
Last Verified: August 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Venetoclax
Leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Neoplasms by Histologic Type
Neoplasms
Midostaurin
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action