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NCT02269579 | Withdrawn Phase 2

• 1 other identifier: CLTR0314-208
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 5

Brief Summary

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

Conditions

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

Keywords

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

Outcome Measures

Primary Outcomes (1)

• Total Drug Plasma PK

  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

  Pre-dose and up to Day 21 during first induction only

Secondary Outcomes (3)

• Serum Copper Levels

  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.

• Urine Sampling

  Days 5-10 during the first induction only.

• Efficacy and Safety

  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.

Study Arms (1)

CPX-351

EXPERIMENTAL

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

Interventions

CPX-351 DRUG

CPX-351

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Jazz Pharmaceuticals: lead

Study Sites (5)

Ronald Reagan UCLA Medical Center

Los Angeles, California, 90095, United States

Location

Shands Cancer Hospital @ University of Florida

Gainesville, Florida, 32610, United States

Location

Franciscan St. Francis Health

Indianapolis, Indiana, 46237, United States

Location

John Theurer Cancer Center @ Hackensack Medical University Medical Center

Hackensack, New Jersey, 07601, United States

Location

Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Myelodysplastic Syndromes; Recurrence

Interventions

CPX-351

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Leukemia, Lymphoid; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Bone Marrow Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Clinical Trial Transparency

  Jazz Pharmaceuticals

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 14, 2014
• First Posted: October 21, 2014
• Study Start: April 1, 2015
• Primary Completion: June 1, 2017
• Study Completion: June 1, 2017
• Last Updated: March 14, 2018

Record last verified: 2018-03

Locations

US (5)