Clinical Trials /

Vyxeos for Re-induction Treatment of Acute Myeloid Leukemia Patients With Persistent Disease After Induction

NCT04049539

Description:

This phase II trial studies the side effects and how well Vyxeos works in treating patients with intermediate and high-risk acute myeloid leukemia who have failed an initial cycle of standard cytarabine and daunorubicin chemotherapy. Vyxeos is a combination of both chemotherapy drugs cytarabine and daunorubicin contained in a liposome. Drugs used in chemotherapy, such as cytarabine and daunorubicin, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Cytarabine and daunorubicin given together in liposomes may have fewer side effects and work better than cytarabine and daunorubicin given alone in patients with acute myeloid leukemia.

Related Conditions:
  • Acute Myeloid Leukemia
Recruiting Status:

Not yet recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Vyxeos for Re-induction Treatment of Acute Myeloid Leukemia Patients With Persistent Disease After Induction
  • Official Title: Open-Label Phase 2 Trial of Vyxeos in Patients With Intermediate and High-Risk Acute Myeloid Leukemia Who Have Failed an Initial Cycle of Standard Cytarabine and Daunorubicin Chemotherapy

Clinical Trial IDs

  • ORG STUDY ID: OSU-19060
  • SECONDARY ID: NCI-2019-04724
  • SECONDARY ID: P30CA016058
  • NCT ID: NCT04049539

Conditions

  • Blasts More Than 5 Percent of Bone Marrow Nucleated Cells
  • Persistent Disease
  • Refractory Acute Myeloid Leukemia

Interventions

DrugSynonymsArms
Liposome-encapsulated Daunorubicin-CytarabineCPX-351, Cytarabine-Daunorubicin Liposome for Injection, Liposomal AraC-Daunorubicin CPX-351, Liposomal Cytarabine-Daunorubicin, Liposome-encapsulated Combination of Daunorubicin and Cytarabine, VyxeosTreatment (liposome-encapsulated daunorubicin-cytarabine)

Purpose

This phase II trial studies the side effects and how well Vyxeos works in treating patients with intermediate and high-risk acute myeloid leukemia who have failed an initial cycle of standard cytarabine and daunorubicin chemotherapy. Vyxeos is a combination of both chemotherapy drugs cytarabine and daunorubicin contained in a liposome. Drugs used in chemotherapy, such as cytarabine and daunorubicin, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Cytarabine and daunorubicin given together in liposomes may have fewer side effects and work better than cytarabine and daunorubicin given alone in patients with acute myeloid leukemia.

Detailed Description

      PRIMARY OBJECTIVES:

      I. To demonstrate the safety and estimate the efficacy of liposome-encapsulated
      daunorubicin-cytarabine (Vyxeos) in acute myeloid leukemia (AML) patients who have failed to
      achieve a hypocellular marrow after an initial course of 7+3.

      SECONDARY AND/OR EXPLORATORY OBJECTIVES:

      I. Determination of rate of morphologic leukemia-free state (MLFS). II. Determination of
      progression-free survival (PFS), and overall survival (OS) at 2 years.

      III. Mass cytometric measurement relative clearance of quiescent leukemia stem/repopulating
      cells (LSCs) and blasts as compared to the same patient's preceding cycle of 7+3 and to a
      separate control population receiving re-induction with traditional 7+3.

      IIIa. Measurement of blast cell cycle fraction before and after Vyxeos treatment.

      IIIb. Relative clearance immunophenotypically abnormal blast and stem cells after Vyxeos.

      IIIc. Comparison of efficacy of blast cell and LSC elimination in patients receiving Vyxeos
      re-induction compared to similar blast cells and LSCs in patients receiving standard 7+3 or
      5+2 re-induction.

      OUTLINE:

      Within 14-26 days after the start of previous cycle of chemotherapy, patients receive
      liposome-encapsulated daunorubicin-cytarabine intravenously (IV) over 90 minutes on days 1,
      3, and 5 in the absence of disease progression or unacceptable toxicity.

      After completion of study treatment, patients are followed up weekly for 60 days, then at
      least monthly for 2 years.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment (liposome-encapsulated daunorubicin-cytarabine)ExperimentalWithin 14-26 days after the start of previous cycle of chemotherapy, patients receive liposome-encapsulated daunorubicin-cytarabine IV over 90 minutes on days 1, 3, and 5 in the absence of disease progression or unacceptable toxicity.
  • Liposome-encapsulated Daunorubicin-Cytarabine

Eligibility Criteria

        Inclusion Criteria:

          -  Subject or their legal guardian must be able to provide written informed consent

          -  Patients must have a diagnosis of acute myeloid leukemia

          -  Patients must have received standard continuous infusion cytarabine and daunorubicin
             (cytarabine 100-200 mg/m^2 by continuous infusion on days 1-7 and daunorubicin 45-90
             mg/m^2 on days 1-3) within the 14-26 days prior to starting trial treatment and have
             documented persistent disease (13-22 days from the start of 7+3 treatment). Patients
             who have received a 7+3 regimen utilizing idarubicin (12 mg/m^2 on days 1-3) in place
             of daunorubicin may enroll. Persistent disease will be defined as bone marrow
             cellularity of > 10-20% and bone marrow blast percentage of > 5-10% or clear evidence
             of immunophenotypically aberrant leukemia cells in the bone marrow. The final
             determination of persistent AML will be made by the treating physician, but must meet
             National Comprehensive Cancer Network (NCCN) criteria for persistent disease.
             Enrollment of patients with less than 20% cellularity or less than 10% blasts will
             require approval of the principal investigator. Patients who received concomitant
             treatment with another targeted therapy for AML (e.g. midostaurin) during initial
             induction may enroll, but will not continue to receive this treatment during Vyxeos
             treatment

          -  Patients must be deemed by the treating physician to be unlikely to achieve complete
             response (CR) without further therapy

          -  Patients must be deemed by the treating physician to be able to tolerate intensive
             chemotherapy (similar to 7+3 chemotherapy)

          -  Normal left ventricular ejection fraction (>= 50% by echocardiography or multi-gated
             acquisition radionuclide angiocardiography [MUGA]) and lifetime daunorubicin dose of
             less than 418 mg/m^2 (including recent course of 7+3)

          -  Eastern Cooperative Oncology Group (ECOG) functional status of 0, 1, or 2

          -  Aspartate aminotransferase (AST) < 5 x upper limit of normal (ULN) for the local
             laboratory

          -  Alanine aminotransferase (ALT) < 5 x ULN for the local laboratory

          -  Total bilirubin < 1.5 x ULN (except for patients with known Gilbert?s syndrome) for
             the local laboratory

          -  Calculated creatinine clearance (according to the Cockcroft-Gault equation) > 40
             mL/min OR serum creatinine < 1.5 x the ULN for the local laboratory

          -  Female patients of childbearing potential must agree to use two forms of contraception
             from screening visit until 6 months following the last dose of study treatment. Female
             patients must have a documented negative pregnancy test

          -  Male patients of childbearing potential having intercourse with females of
             childbearing potential must agree to abstain from heterosexual intercourse or have
             their partner use two forms of contraception from screening visit until 90 days until
             the last dose of study treatment. They must also refrain from sperm donation from
             screening visit until 90 days following the last dose of study treatment

        Exclusion Criteria:

          -  Acute promyelocytic leukemia (or M3 AML)

          -  Patients known to have core binding factor AML (defined as presence of t(8;21),
             inv(16), or other cytogenetically equivalent abnormalities)

          -  Patients known to have inactivating mutations of TP53 or evidence of an absence of p53
             protein activity as indicated by a monosomal karyotype. Monosomal karyotype will be
             defined as two or more monosomies (loss of an entire chromosome or the entire long arm
             of a chromosome [such as 7q-]) or a single monosomy in the setting of a complex
             karyotype. Patients with a complex karyotype without a monosomy are eligible to enroll

          -  Patients that the treating physician does not feel are able to tolerate intensive
             chemotherapy

          -  History of serious (>= grade 3) hypersensitivity reaction to cytarabine, daunorubicin,
             or any component of the formulation

          -  Known Wilson's disease or other symptomatic abnormality of copper metabolism
             (laboratory screening is not required in the absence of clinical or historical
             evidence of Wilson's disease or other problems of copper metabolism)

          -  Total lifetime daunorubicin dose of more than 418 mg/m^2 (including recent course of
             7+3) or equivalent total doses of other anthracycline medications

          -  Pregnancy or inability to use highly effective method of contraception for 6 months
             following last dose of Vyxeos. Potentially fertile patients must have documented
             negative serum pregnancy test. Breastfeeding should be avoided for at least 14 days
             after the last dose Vyxeos

          -  Patients with uncontrolled infection shall not be enrolled until infection is treated
             and brought under control. As infection is a common feature of AML, patients with
             active infections are permitted to enroll provided that the infection is under control

          -  Patients who have received an investigational agent (for any indication) within 5
             half-lives of the agent and until toxicity from this has resolved to grade 1 or less;
             if the half-life of the agent is unknown, patients must wait 4 weeks prior to first
             dose of study treatment. An investigational agent is one for which there is no
             approved indication by the United States (US) Food and Drug Administration (FDA)

          -  Patients with psychological, familial, social, or geographic factors that otherwise
             preclude them from giving informed consent, following the protocol, or potentially
             hamper compliance with study treatment and follow-up

          -  Any other significant medical condition, including psychiatric illness or laboratory
             abnormality, that would preclude the patient participating in the trial or would
             confound the interpretation of the results of the trial

          -  Patients with the following will be excluded: uncontrolled intercurrent illness
             including, but not limited to, symptomatic congestive heart failure, unstable angina
             pectoris, serious cardiac arrhythmia, myocardial infarction within 6 months prior to
             enrollment, New York Heart Association (NYHA) class III or IV heart failure, severe
             uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute
             ischemia or active conduction system abnormalities

          -  Other malignancy currently requiring active therapy (except minor surgery for
             non-melanoma skin cancer and for hormonal/anti-hormonal treatment, e.g. in prostate or
             breast cancer)
      
Maximum Eligible Age:75 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Incidence of adverse events
Time Frame:Up to 60 days
Safety Issue:
Description:Will be measured by the time to count recovery, incidence of symptomatic cardiac dysfunction, incidence of hepatic or renal toxicity, incidence of severe hemorrhage, and incidence of severe infection. Will be summarized by National Cancer Institute Common Terminology Criteria for Adverse Events version 4, and frequency counts will be tabulated with a focus on severe (grade 3+) adverse events and toxicities that are deemed at least possibly related to study treatment. The incidence of specific toxicities will be calculated as the proportion of patients experience these toxicities over all patients who receive any study drug.

Secondary Outcome Measures

Measure:Progression-free survival
Time Frame:Up to 2 years
Safety Issue:
Description:Will be calculated by the method of Kaplan-Meier, with the 2-year estimate provided with 95% confidence interval.
Measure:Overall survival
Time Frame:From the date of the first dose of study treatment to death from any cause, up to 2 years
Safety Issue:
Description:Will be calculated by the method of Kaplan-Meier, with the 2-year estimate provided with 95% confidence interval.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Ohio State University Comprehensive Cancer Center

Last Updated