Clinical Trials /

Pharmacokinetic and Pharmacodynamic Assessment of Treatment With CPX-351 (Cytarabine: Daunorubicin) Liposome for Injection in Acute Leukemias and MDS Patients With Moderate Hepatic Impairment

NCT02269579

Description:

To assess the impact of moderate hepatic impairment on cytarabine and daunorubicin pharmacokinetics and their metabolites following administration of CPX-351.

Related Conditions:
  • Acute Myeloid Leukemia
  • Myelodysplastic Syndromes
Recruiting Status:

Withdrawn

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Pharmacokinetic and Pharmacodynamic Assessment of Treatment With CPX-351 (Cytarabine: Daunorubicin) Liposome for Injection in Acute Leukemias and MDS Patients With Moderate Hepatic Impairment
  • Official Title: An Open Label Phase II Pharmacokinetic and Pharmacodynamic Assessment of Treatment With CPX-351 (Cytarabine: Daunorubicin) Liposome for Injection in Acute Leukemias and MDS Patients With Moderate Hepatic Impairment

Clinical Trial IDs

  • ORG STUDY ID: CLTR0314-208
  • NCT ID: NCT02269579

Conditions

  • Acute Myeloid Leukemia (AML)
  • Acute Lymphoblastic Leukemia (ALL)
  • Myelodysplastic Syndrome (MDS)

Interventions

DrugSynonymsArms
CPX-351CPX-351

Purpose

To assess the impact of moderate hepatic impairment on cytarabine and daunorubicin pharmacokinetics and their metabolites following administration of CPX-351.

Trial Arms

NameTypeDescriptionInterventions
CPX-351ExperimentalStudy Drug CPX-351 will be given intravenously at 100u/m2 on days 1, 3 and 5 by approximately 90 minute infusion.
  • CPX-351

Eligibility Criteria

        Inclusion Criteria:

          -  Ability to understand and voluntarily sign an informed consent form

          -  Age ≥ 18 to ≤ 80 years at the time of signing the informed consent form

          -  Life expectancy of at least 3 months

          -  Pathological confirmation by bone marrow documenting the following:

               -  Newly Diagnosed De novo AML according to WHO criteria except for Acute
                  Promyelocytic Leukemia or patients with known favorable cytogenetics

               -  Newly Diagnosed Secondary AML defined as having a history of an antecedent
                  hematologic disorder (myelodysplastic syndromes [MDS], myeloproliferative disease
                  [MPD]or history of cytotoxic treatment for non-hematologic malignancy)

               -  Patients with relapsed/refractory AML regardless of cytogenetic risk

               -  Patients with relapsed/refractory ALL

               -  Patients with MDS (IPSS score ≥ 1.5)

          -  Eastern Cooperative Oncology Group (ECOG) performance status score of 0-2

          -  Able to adhere to the study visit schedule and other protocol requirements

          -  Laboratory values fulfilling the following:

               -  Serum creatinine ≤ 2.0mg/dL.

               -  Hepatic function with a score of 7-9 points according to the Child-Pugh System

               -  Serum alanine aminotransferase or aspartate aminotransferase < 3 times the ULN.
                  Note:If elevated liver enzymes are related to disease; contact medical monitor to
                  discuss.

          -  Cardiac ejection fraction ≥50% by ECHO or MUGA

          -  Patients with second malignancies in remission may be eligible if there is clinical
             evidence of disease stability for a period of greater than 6 months off cytotoxic
             chemotherapy, documented by imaging, tumor marker studies, etc., at screening.
             Patients maintained on long-term nonchemotherapy treatment, e.g., hormonal therapy,
             are eligible.

          -  All men and women must agree to practice effective contraception during the study
             period if not otherwise documented to be infertile.

        Exclusion Criteria:

          -  Patients with history of and/or current evidence of myocardial impairment (e.g.
             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)

          -  Newly diagnosed patients with Acute promyelocytic leukemia [t(15;17)] or favorable
             cytogenetics, including t(8;21) or inv16

          -  Clinical evidence of active CNS leukemic involvement

          -  Chemotherapy or other investigational anticancer therapeutic drugs within 1 week prior
             to study entry. AEs from prior therapy must have resolved or stabilized so that there
             is no interference with the assessment of efficacy or safety; in the event of rapidly
             proliferative disease, however, the use of hydroxyurea is permitted up to 12 hours
             before study entry. Patients with prior bone marrow or stem cell transplant,
             considered for inclusion, should be discussed with the medical monitor first.

          -  Any serious medical condition or psychiatric illness that would prevent the patient
             from providing informed consent

          -  Patients with prior cumulative anthracycline exposure of greater than 368 mg/m2
             daunorubicin (or equivalent)

          -  Active or uncontrolled infection. Patients with any infection receiving treatment
             (antibiotic,antifungal or antiviral treatment) may be entered into the study but must
             be afebrile and hemodynamically stable for ≥72 hrs. Patients with fevers believed to
             be due to leukemia or MDS are eligible provided a thorough infection work-up is
             negative and the patient is clinically and hemodynamically stable.

          -  Pregnant or lactating women

          -  Hypersensitivity to cytarabine, daunorubicin or liposomal products

          -  History of Wilson's disease or other copper-related metabolic disorder
      
Maximum Eligible Age:80 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Total Drug Plasma PK
Time Frame:Pre-dose and up to Day 21 during first induction only
Safety Issue:
Description:The following parameters will be determined:Tmax, Cmax, AUC (0-last), AUC (0-inf), AUC (0-tau), Clast/λz, λz, t1/2, Vss and CL

Secondary Outcome Measures

Measure:Serum Copper Levels
Time Frame:Pre-dose and up to Day 21 during the first induction only, prior to every course the patient receives, early termination or end of study and 60 day post end of study.
Safety Issue:
Description:The following parameters will be determined:Tmax, Cmax, AUC (0-last), AUC (0-inf), AUC (0-tau), Clast/λz, λz, t1/2, Vss and CL
Measure:Urine Sampling
Time Frame:Days 5-10 during the first induction only.
Safety Issue:
Description:
Measure:Efficacy and Safety
Time Frame:Efficacy and Safety are measured up until the end of study period, SAEs are measured up to 30 days from the end of study period.
Safety Issue:
Description:

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Withdrawn
Lead Sponsor:Jazz Pharmaceuticals

Trial Keywords

  • Newly Diagnosed AML
  • Secondary AML
  • Relapsed/Refractory AML
  • Relapsed/Refractory ALL

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