Clinical Trials /

Liposome-encapsulated Daunorubicin-Cytarabine and Venetoclax in Treating Participants With Relapsed, Refractory or Untreated Acute Myeloid Leukemia

NCT03629171

Description:

This phase II trial studies how well liposome-encapsulated daunorubicin-cytarabine and venetoclax work in treating participants with acute myeloid leukemia that has come back, does not respond to treatment, or has not been treated. Drugs used in chemotherapy, such as liposome-encapsulated daunorubicin-cytarabine and venetoclax, 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.

Related Conditions:
  • Acute Myeloid Leukemia
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Liposome-encapsulated Daunorubicin-Cytarabine and Venetoclax in Treating Participants With Relapsed, Refractory or Untreated Acute Myeloid Leukemia
  • Official Title: Phase II Study of CPX-351 in Combination With Venetoclax in Patients With Acute Myeloid Leukemia (AML)

Clinical Trial IDs

  • ORG STUDY ID: 2017-1055
  • SECONDARY ID: NCI-2018-01589
  • SECONDARY ID: 2017-1055
  • SECONDARY ID: P30CA016672
  • NCT ID: NCT03629171

Conditions

  • Recurrent Acute Myeloid Leukemia
  • Refractory Acute Myeloid Leukemia
  • Untreated Adult 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 (CPX-351, venetoclax)
VenetoclaxABT-0199, ABT-199, ABT199, GDC-0199, RG7601, VenclextaTreatment (CPX-351, venetoclax)

Purpose

This phase II trial studies how well liposome-encapsulated daunorubicin-cytarabine and venetoclax work in treating participants with acute myeloid leukemia that has come back, does not respond to treatment, or has not been treated. Drugs used in chemotherapy, such as liposome-encapsulated daunorubicin-cytarabine and venetoclax, 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.

Detailed Description

      PRIMARY OBJECTIVES:

      I. To assess the efficacy (complete remission [CR], complete remission without blood count
      recovery [CRi], complete remission without platelet recovery [CRp]) of liposome-encapsulated
      daunorubicin-cytarabine (CPX-351) in combination with venetoclax in patients with acute
      myeloid leukemia (AML).

      SECONDARY OBJECTIVES:

      I. To assess safety of CPX-351 in combination with venetoclax in patients with AML.

      II. To assess the event free survival (EFS) and overall survival (OS) in patients with AML.

      EXPLORATORY OBJECTIVES:

      I. To explore biomarkers of response and resistance in AML treated with CPX-351 and
      venetoclax.

      OUTLINE:

      INDUCTION: Participants receive liposome-encapsulated daunorubicin-cytarabine intravenously
      (IV) over 90 minutes on days 1, 3, and 5 of course 1 and on days 1 and 3 of course 2.
      Participants also receive venetoclax orally (PO) once daily (QD) on days 2-21. Treatment
      repeats every 28 days for up to 2 courses in the absence of disease progression or
      unacceptable toxicity.

      CONSOLIDATION: Participants receive liposome-encapsulated daunorubicin-cytarabine IV over 90
      minutes on days 1 and 3 and venetoclax PO QD on days 2-21. Treatment repeats every 28 days
      for up to 4 courses in the absence of disease progression or unacceptable toxicity.

      After completion of study treatment, participants are followed up at 30 days and then every 3
      months for 3 years.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment (CPX-351, venetoclax)ExperimentalINDUCTION: Participants receive liposome-encapsulated daunorubicin-cytarabine IV over 90 minutes on days 1, 3, and 5 of course 1 and on days 1 and 3 of course 2. Participants also receive venetoclax PO QD on days 2-21. Treatment repeats every 28 days for up to 2 courses in the absence of disease progression or unacceptable toxicity. CONSOLIDATION: Participants receive liposome-encapsulated daunorubicin-cytarabine IV over 90 minutes on days 1 and 3 and venetoclax PO QD on days 2-21. Treatment repeats every 28 days for up to 4 courses in the absence of disease progression or unacceptable toxicity.
  • Liposome-encapsulated Daunorubicin-Cytarabine
  • Venetoclax

Eligibility Criteria

        Inclusion Criteria:

          -  For the lead in phase: Patients >= 18 years of age with a diagnosis of relapsed and/or
             refractory AML will be eligible. Patients who have had prior treatment with venetoclax
             will be allowed to participate in the lead in phase

          -  For the dose expansion cohort A (relapsed/refractory [R/R] AML): Patients >= 18 years
             of age with a diagnosis of relapsed and/or refractory AML will be eligible

          -  For the dose expansion cohort B (de novo AML): Patients >= 18 years to 65 years of
             age; patients in this cohort must have received no prior therapy for AML

          -  Prior therapy with hydroxyurea, hematopoietic growth factors, or tretinoin (ATRA) (for
             emergency use for stabilization) is allowed with no washout. A cumulative dose of
             ara-C of up to 3 g for emergency stabilization in patients with rapidly proliferating
             disease is also allowed provided it was administered > 48 hrs prior to enrollment

          -  Bilirubin =< 2 mg/dL

          -  Aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) =< 3 x upper
             limit of normal (ULN) or < 5 x ULN if related to leukemic involvement

          -  Creatinine =< 1.5 x ULN

          -  Known cardiac ejection fraction of > or = 45% within the past 3 months

          -  Eastern Cooperative Oncology Group (ECOG) performance status of =< 2

          -  A negative urine or serum pregnancy test is required within 1 week for all women of
             childbearing potential prior to enrolling on this trial. A woman of childbearing
             potential is defined as a woman who has not been naturally postmenopausal for at least
             12 consecutive months, or who had no previous surgical sterilization

          -  Patient must have the ability to understand the requirements of the study and signed
             informed consent. A signed informed consent by the patient or his legally authorized
             representative is required prior to their enrollment on the protocol

        Exclusion Criteria:

          -  Pregnant women are excluded from this study because the agents used in this study have
             the potential for teratogenic or abortifacient effects. Because there is a potential
             risk for adverse events in nursing infants secondary to treatment of the mother with
             the chemotherapy agents, breastfeeding should also be avoided

          -  Uncontrolled intercurrent illness including, but not limited to active uncontrolled
             infection, symptomatic congestive heart failure (New York Heart Association [NYHA]
             class III or IV), unstable angina pectoris, clinically significant cardiac arrhythmia,
             or psychiatric illness/social situations that would limit compliance with study
             requirements

          -  Patient with documented hypersensitivity to any of the components of the chemotherapy
             program

          -  Patients with acute promyelocytic leukemia (M3) or core-binding factor AML

          -  Patients with active central nervous system (CNS) leukemia are excluded since the
             antileukemia activity of the treatment components against CNS leukemia are not known

          -  Men and women of childbearing potential who do not practice contraception. Women of
             childbearing potential and men must agree to use contraception prior to study entry
             and for the duration of study participation

          -  Prior treatment with CPX-351 or venetoclax. Patients with prior treatment with
             venetoclax will be allowed in the lead-in phase
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Achievement of composite complete remission
Time Frame:Up to 3 courses (84 days)
Safety Issue:
Description:Defined as complete remission/complete remission without blood count recovery/complete remission without platelet recovery. Will be monitored simultaneously using the Bayesian approach of Thall, Simon, Estey. Will be estimated along with the 95% credible interval.

Secondary Outcome Measures

Measure:Event-free survival
Time Frame:Number of days from the date of treatment initiation up to 1 year
Safety Issue:
Description:Will be estimated using the method of Kaplan and Meier. Comparisons of time-to-event endpoints by important subgroups will be made using the log-rank tests.
Measure:Overall survival
Time Frame:Time from treatment start till death or last follow-up, assessed up to 1 year
Safety Issue:
Description:Will be estimated using the method of Kaplan and Meier. Comparisons of time-to-event endpoints by important subgroups will be made using the log-rank tests.
Measure:Biomarker changes
Time Frame:Baseline up to 1 year
Safety Issue:
Description:The comparison regarding biomarkers between response and non-response will be conducted by two-sample t-test if the data is normally distributed, otherwise Wilcoxon rank sum test will be used.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:M.D. Anderson Cancer Center

Last Updated

September 4, 2019