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

Sponsor

Jazz Pharmaceuticals (Industry)

Overall Status

Withdrawn

CT.gov ID

NCT02269579

Collaborator

(none)

Enrollment

Locations

Arm

Duration (Months)

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

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

Study Design

Study Type:

Interventional

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 :

Apr 1, 2015

Anticipated Primary Completion Date :

Jun 1, 2017

Anticipated Study Completion Date :

Jun 1, 2017

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

Total Drug Plasma PK [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

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.]
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
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.]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 80 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Ronald Reagan UCLA Medical Center	Los Angeles	California	United States	90095
2	Shands Cancer Hospital @ University of Florida	Gainesville	Florida	United States	32610
3	Franciscan St. Francis Health	Indianapolis	Indiana	United States	46237
4	John Theurer Cancer Center @ Hackensack Medical University Medical Center	Hackensack	New Jersey	United States	07601
5	Medical College of Wisconsin	Milwaukee	Wisconsin	United States	53226