Multicenter Study of CPX-351(Cytarabine:Daunorubicin) Liposome Injection in Patients With Advanced Hematologic Cancer.

Sponsor

Jazz Pharmaceuticals (Industry)

Overall Status

Completed

CT.gov ID

NCT00389428

Collaborator

(none)

Enrollment

Locations

Duration (Months)

Patients Per Site

0.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The primary objective of this study is to determine the recommended dose of CPX-351 for use in a phase 2 efficacy study in patients with leukemia. Secondarily, the study will assess the safety, serious adverse effects and how the body handles CPX-351. Preliminary evidence of antitumor activity will also be determined.

Condition or Disease	Intervention/Treatment	Phase
Hematologic Neoplasms	Drug: CPX-351 (Cytarabine:Daunorubicin) Liposome Injection	Phase 1

Detailed Description

CPX-351 is a liposomal formulation of a fixed combination of the antineoplastic drugs cytarabine and daunorubicin. The two drugs are present inside the liposome in a 5:1 molar ratio. The development of CPX-351 (cytarabine:daunorubicin) Liposome Injection was based on

defining a synergistic ratio of the two active moieties, cytarabine and daunorubicin, using cell-based screening assays and 2) designing a liposomal drug carrier to maintain this ratio after intravenous administration. CPX-351 was found to be more active in in vivo models of cancer than combinations of conventional cytarabine and daunorubicin. Both cytarabine and daunorubicin are active chemotherapeutic agents, each approved for clinical use in the United States for the treatment of hematological neoplasms.

CPX-351 is being developed with the hypothesis that it is superior to the currently used regimen of cytarabine and daunorubicin in the treatment of acute leukemia. This phase I study will determine the dose to carry forward into phase II trials.

Study Design

Study Type:

Interventional

Actual Enrollment :

48 participants

Allocation:

Non-Randomized

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Phase 1 Study of CPX-351(Cytarabine:Daunorubicin) Liposome Injection in Patients With Advanced Hematologic Malignancies.

Study Start Date :

Sep 1, 2006

Actual Primary Completion Date :

Dec 1, 2008

Actual Study Completion Date :

Dec 1, 2009

Outcome Measures

Primary Outcome Measures

To determine the maximum tolerated dose (MTD) for use in phase 2 []

Secondary Outcome Measures

To evaluate the safety and dose-limiting toxicities (DLT) of CPX-351. []
To determine the pharmacokinetic parameters of CPX-351 administered in this schedule. []
To assess preliminary efficacy information of CPX-351 administered in this schedule in patients with advanced leukemias. []

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Ability to understand and voluntarily sign an informed consent form
Age > 18 years at the time of signing the informed consent form
Pathological confirmation of leukemia or myelodysplastic syndrome.
AML according to WHO criteria; except for core-binding factor AMLs (t(8;21), inv(16) or t(16;16)) and APL
ALL
MDS
Patients with AML include the following:
Patients in 2nd or greater relapse
Patients in first relapse with initial CR duration lasting <6 months
Patients in first relapse refractory to induction therapy
Patients with primary refractory AML
Patients with ALL include the following
Patients with T-cell ALL refractory or in relapse following nelarabine
Patients with other ALL that is refractory or in relapse.
Patients with MDS include the following:
The subset of RAEB-2 patients with >10% blasts with at least 1 prior therapy that includes a hypomethylating agent.
Previously untreated chemotherapy induced AML
Eastern Cooperative Oncology Group (ECOG) performance status score of 0,1 or 2
Able to adhere to the study visit schedule and other protocol requirements
Life expectancy of at least 12 weeks
Laboratory values fulfilling the following:
Serum creatinine < 1.5 mg/dL
Serum total bilirubin < 1.5 mg/dL
Serum alanine aminotransferase or aspartate aminotransferase < 150 IU/liter Note: If elevated liver enzymes are related to disease; contact medical monitor to discuss.
Cardiac ejection fraction > 50% by MUGA scan or echocardiography
All men and women must agree to practice effective contraception during the study period if not otherwise documented to be infertile.

Exclusion Criteria:

Any serious medical condition, laboratory abnormality or psychiatric illness that would prevent the patient from signing the informed consent form
Chemotherapy or other investigational anticancer therapeutic drugs in the two weeks prior to study entry; in the event of rapidly proliferative disease, however, the use of hydroxyurea is permitted up to 24 hours before study entry
Clinical evidence of active CNS leukemic involvement
Pregnant or lactating women
Clinically significant cardiac disease (New York Heart Association Class III or IV)
Severe debilitating pulmonary disease
Active and uncontrolled infection. Patients with an infection under active treatment with antibiotics and whose infection is controlled may be entered into the study
Current evidence of invasive fungal infection (blood or tissue culture); HIV or hepatitis C infection
Hypersensitivity to cytarabine, daunorubicin or liposomal products
History of Wilson's disease or other copper-related disorder

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Georgetown University Medical Center	Washington	District of Columbia	United States	20007
2	H. Lee Moffit Cancer Center & Research Institute at the University of S. Florida	Tampa	Florida	United States	33612-9497
3	North Shore University Hospital	Manhasset	New York	United States	11030
4	New York Presbyterian Hospital Weill Medical College of Cornell University	New York	New York	United States	10021

Sponsors and Collaborators

Jazz Pharmaceuticals

Investigators

Study Director: Arthur Louie, M.D., Jazz Pharmaceuticals
Principal Investigator: Jonathan Kolitz, M.D., New York School of Medicine at North Shore University Hospital