Clinical trial NCT00822094: Trial of CPX-351 in Adult Patients With First Relapse Acute Myeloid Leukemia (AML)
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Acute Myeloid Leukemia
Keywords: Acute
Myeloid
Leukemia
Adult
First
Relapse
AML
Acute Myelogenous leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Acute myelocytic leukemia
Lead sponsor: Jazz Pharmaceuticals
Sponsor class: INDUSTRY
Collaborators: name: The Leukemia and Lymphoma Society
First posted: 2009-01-14
Enrollment: 126
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Proportion of Subjects Surviving at 1 Year
timeFrame: Up to 1 year from randomization
Secondary outcomes:
measure: Complete Remission Rate
timeFrame: Following 1st induction, following 2nd induction if applicable
measure: Event Free Survival
timeFrame: Up to 1 year from randomization
measure: Remission Duration
timeFrame: Following achievement of CR and up to 1 year from randomization
measure: Rate of Aplasia
timeFrame: Up to 1 year from randomization
measure: Rate of Stem Cell Transplant
timeFrame: Up to 1 year from randomization
Other outcomes:
Locations:
city: Tucson
country: United States
facility: Arizona Cancer Center
state: Arizona
city: Los Angeles
country: United States
facility: UCLA
state: California
city: Los Angeles
country: United States
facility: Cedars Sinai Medical Center
state: California
city: Sacramento
country: United States
facility: UC Davis Cancer Center
state: California
city: Aurora
country: United States
facility: University of Colorado Cancer Center
state: Colorado
city: Chicago
country: United States
facility: Northwestern University Robert H. Lurie Comprehensive Cancer Center
state: Illinois
city: Chicago
country: United States
facility: Rush University Medical Center
state: Illinois
city: Chicago
country: United States
facility: University of Chicago Medical Center Section of Hematology/Oncology
state: Illinois
city: Beech Grove
country: United States
facility: St. Francis Cancer Center
state: Indiana
city: Louisville
country: United States
facility: University of Louisville Brown Cancer Center
state: Kentucky
city: Waterville
country: United States
facility: Maine General Medical Center Harold Alfond Center for Cancer Care
state: Maine
city: Baltimore
country: United States
facility: Johns Hopkins University
state: Maryland
city: Saint Louis
country: United States
facility: St. Louis University Medical Center
state: Missouri
city: Hackensack
country: United States
facility: The Cancer Center, Hackensack University Medical Center
state: New Jersey
city: Lake Success
country: United States
facility: North Shore LIJ Center for Advanced Medicine Monter Cancer Center
state: New York
city: New York
country: United States
facility: Weil Cornell Medical Center
state: New York
city: New York
country: United States
facility: New York Medical College
state: New York
city: The Bronx
country: United States
facility: Montefiore Medical Center
state: New York
city: Charlotte
country: United States
facility: Blumenthal Cancer Center/Mecklenburg Medical Group
state: North Carolina
city: Durham
country: United States
facility: Duke Comprehensive Cancer Center
state: North Carolina
city: Cincinnati
country: United States
facility: Jewish Hospital of Cincinatti
state: Ohio
city: Portland
country: United States
facility: Oregon Health and Science University
state: Oregon
city: Bethlehem
country: United States
facility: Oncology and Hematology at Lehigh Valley
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Western Pennsylvania Hospital
state: Pennsylvania
city: Galveston
country: United States
facility: UTMB Comprehensive Cancer Center
state: Texas
city: Houston
country: United States
facility: M.D. Anderson Cancer Center
state: Texas
city: Lubbock
country: United States
facility: Joe Arrington Cancer Center
state: Texas
city: Lubbock
country: United States
facility: Texas Tech University Health Sciences Center
state: Texas
city: San Antonio
country: United States
facility: Cancer Therapy and Research Center at The University of TX Health Science Center
state: Texas
city: Salt Lake City
country: United States
facility: Intermountain LDS Hospital
state: Utah
city: Milwaukee
country: United States
facility: Medical College of Wisconsin
state: Wisconsin
city: Vancouver
country: Canada
facility: Vancouver General Hospital/ British Columbia Cancer Agency
state: British Columbia
city: Winnipeg
country: Canada
facility: Cancer Care Manitoba
state: Manitoba
city: Lille Cedex
country: France
facility: Service des Maladies du Sang CHU de Lille, Hopital Claude Huriez
city: Pessac
country: France
facility: Service des Maladies du Sang Hopital Haut-Leveque
city: Toulouse Cedex 09
country: France
facility: Service d'Hématologie CHU Toulouse-Hôpital Purpan
city: Vandoeuvre les Nancy Cedex
country: France
facility: Service d'Hématologie et Médecine Interne CHU de Nancy-Hôpital de Brabois
city: Gdansk
country: Poland
facility: Klinika Hematologii i Transplantologii
city: Lodz
country: Poland
facility: Wojewódzki Szpital Specjalistyczny im. M. Kopernika
city: Opole
country: Poland
facility: Oddział Hematologii
city: Warszawa
country: Poland
facility: Instytut Hematologii i Transfuzjologii
city: Wroclaw
country: Poland
facility: Akademia Medyczna we Wroclawlu
Study officials:
affiliation: North Shore University Hospital
name: Jonathan Kolitz, MD
role: PRINCIPAL_INVESTIGATOR
References: