Trial of CPX-351 in Adult Patients With First Relapse Acute Myeloid Leukemia (AML)

Acute Myeloid Leukemia Clinical Trial

Official title:

Phase IIB, Multicenter, Randomized, Open-Label Trial Of CPX-351 (Cytarabine : Daunorubicin) Liposome Injection Versus Intensive Salvage Therapy In Adult Patients ≤ 65 Years Old With AML In First Relapse Following An Initial CR > 1 Month Duration

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00822094
• Other study ID #: CLTR0308-205
• Status: Completed
• Phase: Phase 2
• First received: January 12, 2009
• Last updated: October 20, 2017
• Start date: February 2009
• Est. completion date: January 2012

Study information

• Verified date: October 2017
• Source: Jazz Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The study investigates if CPX-351 will be a) more effective than the standard intensive salvage AML treatment and b) more tolerable than the standard intensive salvage treatment regimens.

The study compares the investigational product CPX-351 vs the standard intensive salvage treatment for first relapse AML patients.

Description:

This study is a randomized, open-label, parallel-arm, fixed-dose, standard therapy controlled Phase IIB trial. Study enrollment duration is expected to be approximately 12-18 months. On entry, patients are randomized to receive either CPX-351 or intensive first salvage treatment.

Patients are stratified to balance the likelihood of obtaining a CR and the duration of CR between the two arms.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 126
• Est. completion date: January 2012
• Est. primary completion date: December 2011
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

• Ability to understand and voluntarily sign an informed consent form

• Age =18 and =65 years at the time of relapse

• Pathological confirmation of relapsed AML after initial CR of >1 month duration

• 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

• Serum alanine aminotransferase or aspartate aminotransferase <3xULN Note: If elevated liver enzymes are related to disease; contact medical monitor to discuss.

• Cardiac ejection fraction > 50% by echocardiography or MUGA scan

• All men and women must agree to practice effective contraception during the study period and for 3 months afterward if not otherwise documented to be infertile.

Exclusion Criteria:

• Patients with active second malignancies are excluded. Patients with second malignancies in remission may be eligible if there is no clinical evidence of active disease, documented by imaging, with tumor marker studies, etc., at screening. Patients maintained on long-term non-chemotherapy treatment, e.g., hormonal therapy, are eligible. In all cases, the second malignancy and its non-chemotherapy treatment must not interfere with the investigators ability to assess the safety or efficacy of the study treatment

• Patients with acute promyelocytic leukemia [t(15;17)]

• Total lifetime anthracycline exposure exceeding the equivalent of 368 mg/m2 of daunorubicin (or equivalent) prior to start of study therapy

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

• Administration of any antineoplastic therapy within 4 weeks of therapy; intended to treat first relapse. In the event of rapidly proliferative disease use of hydroxyurea is permitted until 24 hours before the start of study treatment

• Clinical evidence of active CNS leukemia

• 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 New York Heart Association Class III or IV staging

• Active and uncontrolled infection. Patients with a bacterial infection receiving treatment with antibiotics may be entered into the study if they are afebrile and hemodynamically stable for >72 hrs.

• Current evidence of invasive fungal infection (blood or tissue culture); active hepatitis C infection or known HIV infection

• Hypersensitivity to cytarabine, daunorubicin or liposomal products

• History of Wilson's disease or other copper-related disorder

• Patients with a history of severe toxicity related to receiving conventional dose cytarabine in first line treatment (approximately 100mg/m2/d for <7 days) are excluded. Patients who experienced unacceptable toxicities while receiving high dose cytarabine (approximately 3000mg/m2 for 6 doses) will not be treated again with the same regimen, but could be randomized to treatment with conventional dose cytarabine regimens where the risk of major toxicity is less.

• Woman who are pregnant or breast feeding

Related Conditions & MeSH terms

• Acute Myeloid Leukemia
• Leukemia
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute
• Recurrence

Intervention

Drug:
• CPX-351

• Intensive Salvage Therapy

Locations

Country	Name	City	State
Canada	Vancouver General Hospital/ British Columbia Cancer Agency	Vancouver	British Columbia
Canada	Cancer Care Manitoba	Winnipeg	Manitoba
France	Service des Maladies du Sang CHU de Lille, Hopital Claude Huriez	Lille Cedex
France	Service des Maladies du Sang Hopital Haut-Leveque	Pessac
France	Service d'Hématologie CHU Toulouse-Hôpital Purpan	Toulouse Cedex 09
France	Service d'Hématologie et Médecine Interne CHU de Nancy-Hôpital de Brabois	Vandoeuvre les Nancy Cedex
Poland	Klinika Hematologii i Transplantologii	Gdansk
Poland	Wojewódzki Szpital Specjalistyczny im. M. Kopernika	Lodz
Poland	Oddzial Hematologii	Opole
Poland	Instytut Hematologii i Transfuzjologii	Warszawa
Poland	Akademia Medyczna we Wroclawlu	Wroclaw
United States	University of Colorado Cancer Center	Aurora	Colorado
United States	Johns Hopkins University	Baltimore	Maryland
United States	St. Francis Cancer Center	Beech Grove	Indiana
United States	Oncology and Hematology at Lehigh Valley	Bethlehem	Pennsylvania
United States	Blumenthal Cancer Center/Mecklenburg Medical Group	Charlotte	North Carolina
United States	Northwestern University Robert H. Lurie Comprehensive Cancer Center	Chicago	Illinois
United States	Rush University Medical Center	Chicago	Illinois
United States	University of Chicago Medical Center Section of Hematology/Oncology	Chicago	Illinois
United States	Jewish Hospital of Cincinatti	Cincinnati	Ohio
United States	Duke Comprehensive Cancer Center	Durham	North Carolina
United States	UTMB Comprehensive Cancer Center	Galveston	Texas
United States	The Cancer Center, Hackensack University Medical Center	Hackensack	New Jersey
United States	M.D. Anderson Cancer Center	Houston	Texas
United States	North Shore LIJ Center for Advanced Medicine Monter Cancer Center	Lake Success	New York
United States	Cedars Sinai Medical Center	Los Angeles	California
United States	UCLA	Los Angeles	California
United States	University of Louisville Brown Cancer Center	Louisville	Kentucky
United States	Joe Arrington Cancer Center	Lubbock	Texas
United States	Texas Tech University Health Sciences Center	Lubbock	Texas
United States	Medical College of Wisconsin	Milwaukee	Wisconsin
United States	New York Medical College	New York	New York
United States	Weil Cornell Medical Center	New York	New York
United States	Western Pennsylvania Hospital	Pittsburgh	Pennsylvania
United States	Oregon Health and Science University	Portland	Oregon
United States	UC Davis Cancer Center	Sacramento	California
United States	St. Louis University Medical Center	Saint Louis	Missouri
United States	Intermountain LDS Hospital	Salt Lake City	Utah
United States	Cancer Therapy and Research Center at The University of TX Health Science Center	San Antonio	Texas
United States	Montefiore Medical Center	The Bronx	New York
United States	Arizona Cancer Center	Tucson	Arizona
United States	Maine General Medical Center Harold Alfond Center for Cancer Care	Waterville	Maine

Sponsors (2)

Lead Sponsor	Collaborator
Jazz Pharmaceuticals	The Leukemia and Lymphoma Society

Countries where clinical trial is conducted

United States,  Canada,  France,  Poland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Proportion of Subjects Surviving at 1 Year	The proportion of subjects surviving at 1 year was evaluated separately for each arm by the number of subjects alive at 1 year divided by the total number of subjects.	Up to 1 year from randomization
Secondary	Complete Remission Rate		Following 1st induction, following 2nd induction if applicable
Secondary	Event Free Survival	Progression EFS median	Up to 1 year from randomization
Secondary	Remission Duration	Remission duration was measured from the time the criteria for CR were first met until the first date that disease relapse was objectively documented or until subject death.	Following achievement of CR and up to 1 year from randomization
Secondary	Rate of Aplasia	Patients with Aplasia During Study	Up to 1 year from randomization
Secondary	Rate of Stem Cell Transplant	Number of patients transferred for stem cell transplant	Up to 1 year from randomization

External Links

•   Company Website
•   The Leukemia and Lymphoma Society