Phase III Study of CPX-351 Versus 7+3 in Patients 60-75 Years Old With Untreated High Risk (Secondary) Acute Myeloid Leukemia

High Risk Acute Myeloid Leukemia Clinical Trial

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Official title:

Phase III, Multicenter, Randomized, Trial of CPX-351 (Cytarabine:Daunorubicin) Liposome Injection Versus Cytarabine and Daunorubicin in Patients 60-75 Years of Age With Untreated High Risk (Secondary) AML

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01696084
• Other study ID #: CLTR0310-301
• Status: Completed
• Phase: Phase 3
• 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
• 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

Related Conditions & MeSH terms

• High Risk Acute Myeloid Leukemia
• Leukemia
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute

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