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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT02269579
Recruitment Status : Withdrawn
First Posted : October 21, 2014
Last Update Posted : March 14, 2018
Information provided by (Responsible Party):
Jazz Pharmaceuticals

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

Condition or disease Intervention/treatment Phase
Acute Myeloid Leukemia (AML) Acute Lymphoblastic Leukemia (ALL) Myelodysplastic Syndrome (MDS) Drug: CPX-351 Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 0 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Study Start Date : April 2015
Estimated Primary Completion Date : June 2017
Estimated Study Completion Date : June 2017

Arm Intervention/treatment
Experimental: CPX-351
Study Drug CPX-351 will be given intravenously at 100u/m2 on days 1, 3 and 5 by approximately 90 minute infusion.
Drug: CPX-351

Primary Outcome Measures :
  1. Total Drug Plasma PK [ Time Frame: Pre-dose and up to Day 21 during first induction only ]
    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 :
  1. 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. ]
    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

  2. Urine Sampling [ Time Frame: Days 5-10 during the first induction only. ]
  3. 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. ]

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

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 identifier (NCT number): NCT02269579

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United States, California
Ronald Reagan UCLA Medical Center
Los Angeles, California, United States, 90095
United States, Florida
Shands Cancer Hospital @ University of Florida
Gainesville, Florida, United States, 32610
United States, Indiana
Franciscan St. Francis Health
Indianapolis, Indiana, United States, 46237
United States, New Jersey
John Theurer Cancer Center @ Hackensack Medical University Medical Center
Hackensack, New Jersey, United States, 07601
United States, Wisconsin
Medical College of Wisconsin
Milwaukee, Wisconsin, United States, 53226
Sponsors and Collaborators
Jazz Pharmaceuticals
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Study Director: Clinical Trial Transparency Jazz Pharmaceuticals
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Responsible Party: Jazz Pharmaceuticals Identifier: NCT02269579    
Other Study ID Numbers: CLTR0314-208
First Posted: October 21, 2014    Key Record Dates
Last Update Posted: March 14, 2018
Last Verified: March 2018
Keywords provided by Jazz Pharmaceuticals:
Newly Diagnosed AML
Secondary AML
Relapsed/Refractory AML
Relapsed/Refractory ALL
Additional relevant MeSH terms:
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Leukemia, Myeloid, Acute
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Myelodysplastic Syndromes
Neoplasms by Histologic Type
Leukemia, Myeloid
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Leukemia, Lymphoid
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases