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Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT01696084
Other study ID # CLTR0310-301
Secondary ID
Status Completed
Phase Phase 3
First received
Last updated
Start date December 13, 2012
Est. completion date December 31, 2015

Study information

Verified date July 2020
Source Jazz Pharmaceuticals
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

To confirm the efficacy of CPX-351 compared to 7+3 as first line therapy in elderly patients (60-75 yrs) with high risk (secondary) Acute Myeloid Leukemia. The primary efficacy endpoint will be overall survival.


Recruitment information / eligibility

Status Completed
Enrollment 309
Est. completion date December 31, 2015
Est. primary completion date December 31, 2015
Accepts healthy volunteers No
Gender All
Age group 60 Years to 75 Years
Eligibility Inclusion Criteria:

- Ability to understand and voluntarily give informed consent

- Age 60-75 years at the time of diagnosis of AML

- Pathological diagnosis of AML according to WHO criteria (with at least 20% blasts in the peripheral blood or bone marrow)

- Confirmation of:

- Therapy related AML: t-AML must have a documented history of prior cytotoxic therapy or ionizing radiotherapy for an unrelated disease

- AML with a history of myelodysplasia: MDSAML must have bone marrow documentation of prior MDS

- AML with a history of CMMoL: CMMoLAML must have bone marrow documentation of prior CMMoL

- De novo AML with karyotypic abnormalities characteristic of MDS: de novoAML must have cytogenetics with abnormalities per WHO.

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

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

- Laboratory values fulfilling the following:

- Serum creatinine < 2.0 mg/dL

- Serum total bilirubin < 2.0 mg/dL, patients with Gilbert's Syndrome should contact the medical monitor

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

- Cardiac ejection fraction = 50% by echocardiography 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 non-chemotherapy treatment, e.g., hormonal therapy, are eligible.

Exclusion Criteria:

- Except for CMMoL, patients with history of myeloproliferative neoplasms (MPN) (defined as a history of essential thrombocytosis or polycythemia vera, or idiopathic myelofibrosis prior to the diagnosis of AML) or combined MDS/MPN are not eligible.

- Acute promyelocytic leukemia [t(15;17)] or favorable cytogenetics, including t(8;21) or inv16 if known at the time of randomization.

- Clinical evidence of active CNS leukemia

- Patients with active (uncontrolled, metastatic) second malignancies are excluded.

- Prior treatment intended for induction therapy of AML; only hydroxyurea is permitted for control of blood counts. For example, a patient with MDS that changes HMA dose and schedule after the diagnosis of AML is excluded. AML-type therapy, such as cytarabine alone (>1g/m2/day) or cytarabine plus an anthracycline as well as prior HSCT are also excluded.

- Administration of any therapy for MDS (conventional or investigational) must be completed by 2 weeks prior to of the first dose of study drug; in the event of rapidly proliferative disease use of hydroxyurea is permitted until 24 hours before the start of study treatment. Toxicities associated with prior MDS therapy must have recovered to grade 1 or less prior to start of treatment.

- Any major surgery or radiation therapy within four weeks.

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

- Any serious medical condition, laboratory abnormality or psychiatric illness that would prevent obtaining informed consent

- Patients with myocardial impairment of any cause (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)

- Active or uncontrolled infection. Patients with an infection receiving treatment (antibiotic, antifungal or antiviral treatment) may be entered into the study but must be afebrile and hemodynamically stable for =72 hrs.

- Current evidence of invasive fungal infection (blood or tissue culture); patients with recent fungal infection must have a subsequent negative cultures to be eligible; known HIV (new testing not required) or evidence of active hepatitis B or C infection (with rising transaminase values)

- Hypersensitivity to cytarabine, daunorubicin or liposomal products

- History of Wilson's disease or other copper-metabolism disorder

Study Design


Intervention

Drug:
CPX-351
First induction: 100 units/m2 by 90-minute IV infusion on Days 1, 3, 5. Second induction: 100 units/m2 by 90-minute IV infusion on Days 1 and 3. Consolidation therapy: 65 units/m2 by 90-minute IV infusion on Days 1 and 3.
7+3 (cytarabine and daunorubicin)
First induction: 7+3 was administered as: cytarabine at a dose of 100 mg/m2/day on Days 1 through 7 by continuous infusion, and daunorubicin at a dose of 60 mg/m2/day on Days 1, 2, and 3. Second induction: 5+2 was administered as: cytarabine at a dose of 100 mg/m2/day on Days 1 through 5 by continuous infusion and daunorubicin at a dose of 60 mg/m2/day on Days 1 and 2. Consolidation therapy: 5+2 was administered as: cytarabine at a dose of 100 mg/m2/day on Days 1 through 5 by continuous infusion, and daunorubicin at a dose of 60 mg/m2/day on Days 1 and 2.

Locations

Country Name City State
Canada University of Alberta Hospital Edmonton Alberta
Canada Hopital Maisonneuve-Rosemont Montreal Quebec
Canada Princess Margaret Hospital Toronto Ontario
Canada British Columbia Cancer Center Vancouver British Columbia
United States University of Michigan Ann Arbor Michigan
United States Northside Hospital Atlanta Georgia
United States University of Alabama at Birmingham Birmingham Alabama
United States Dana-Farber Cancer Institute Boston Massachusetts
United States Montefiore Medical Center Bronx New York
United States University of North Carolina at Chapel Hill Chapel Hill North Carolina
United States Medical University of South Carolina Charleston South Carolina
United States Northwestern University Chicago Illinois
United States Rush University Medical Center Chicago Illinois
United States University of Chicago Chicago Illinois
United States University of Missouri Columbia Missouri
United States Baylor Research Insitute Dallas Texas
United States Duke University Medical Center Durham North Carolina
United States University of Florida Gainesville Florida
United States Hackensack University Medical Center Hackensack New Jersey
United States M.D. Anderson Cancer Center Houston Texas
United States Franciscan St. Francis Health Indianapolis Indiana
United States University of Kansas Medical Center Kansas City Kansas
United States Dartmouth Hitchcock Medical Center Lebanon New Hampshire
United States North Shore LIJ Health System Long Island City New York
United States UCLA Los Angeles California
United States Medical College of Wisconsin Milwaukee Wisconsin
United States University of Minnesota Minneapolis Minnesota
United States Sarah Cannon Research Institute Nashville Tennessee
United States Vanderbilt University Nashville Tennessee
United States Yale University New Haven Connecticut
United States Columbia University New York New York
United States Cornell U, Weill Medical College New York New York
United States Fox Chase Cancer Center Philadelphia Pennsylvania
United States UPMC Pittsburgh Pennsylvania
United States Oregon Health and Science University Portland Oregon
United States Providence Portland Medical Center Portland Oregon
United States Washington University Saint Louis Missouri
United States University of CA San Diego San Diego California
United States Fred Hutchinson Cancer Research Center Seattle Washington
United States Stanford University Stanford California
United States H. Lee Moffitt Cancer Center Tampa Florida
United States New York Medical College Valhalla New York
United States Wake Forest University Health Services Winston-Salem North Carolina

Sponsors (2)

Lead Sponsor Collaborator
Jazz Pharmaceuticals The Leukemia and Lymphoma Society

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type Measure Description Time frame Safety issue
Primary Overall Survival Overall survival was measured from the date of randomization to death from any cause, subjects not known to have died by the last follow-up were censored on the date they were last known to be alive. From the date of randomization to death from any cause
Secondary Proportion of Subjects With a Response Complete Remission (CR) Post Induction
Secondary Event-free Survival All randomized subjects were assessed for event-free survival (EFS). EFS was defined as the time from study randomization to the date of induction treatment failure (persistent disease), relapse from CR or CRi or death from any cause, whichever came first. Subjects alive and not known to have any of these events were censored on thee date they were last examined on study. From the date of randomization to the date that persistent disease was documented or the date of relapse after CR or death, whichever came first
Secondary Remission Duration Only subjects achieving CR or CRi were assessed for remission duration. From the date of achievement of a remission until the date of relapse or death from any cause
Secondary Rate of Achieving Morphologic Leukemia-free State All randomized subjects with at least 1 evaluable postrandomization bone marrow assessment performed on or after Day 14 after the last induction were assessed for MLFS. Day 14
Secondary Proportion of Subjects Receiving a Stem Cell Transplant The number and percentage of subjects transferred for HSCT after induction treatment was recorded. Post Induction
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