Clinical trial NCT00004933: Homoharringtonine Compared With Hydroxyurea for Chronic Myelogenous Leukemia That Has Not Responded to Interferon Alfa
Official title: A Phase III Study of Interferon-Refractory Patients With BCR/ABL(+) Chronic Myelogenous Leukemia (CML) Treated With Homoharringtonine (NSC #141633) vs. Hydroxyurea
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Leukemia
Keywords: relapsing chronic myelogenous leukemia
chronic phase chronic myelogenous leukemia
Philadelphia chromosome positive chronic myelogenous leukemia
Lead sponsor: Alliance for Clinical Trials in Oncology
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2004-04-28
Enrollment: 5
Sex: ALL
Minimum age (years): 16
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. It is not yet known if homoharringtonine is more effective than hydroxyurea for chronic myelogenous leukemia that has not responded to interferon alfa.

PURPOSE: Randomized phase III trial to compare the effectiveness of homoharringtonine with that of hydroxyurea in treating patients who have chronic myelogenous leukemia that has not responded to interferon alfa.

Detailed description: OBJECTIVES: I. Compare the overall survival of interferon alfa refractory chronic myelogenous leukemia patients treated with homoharringtonine to those treated with hydroxyurea. II. Compare the time to progression of these patients treated with these two drugs. III. Estimate the complete and major cytogenetic response and describe the serial cytogenetics of these patients treated with these two drugs.

OUTLINE: This is a randomized study. Patients are randomized to receive one of two treatments. Arm I: Induction: Patients receive homoharringtonine IV continuously over 24 hours daily for 14 days. Induction continues every 28 days for a maximum of 6 courses or until hematopoietic recovery. Maintenance: Patients receive homoharringtonine IV continuously over 24 hours daily for 5 days. Treatment repeats every 28 days. Arm II: Induction: Patients receive oral hydroxyurea daily for 28 days until acceptable blood counts are achieved. Maintenance: Patients receive oral hydroxyurea daily every 28 days to maintain acceptable blood counts. Treatment in both arms continues for a minimum of 6 courses in the absence of disease progression or unacceptable toxicity. Patients are followed every 6 months for a maximum of 10 years.

PROJECTED ACCRUAL: A total of 480 patients (240 per arm) will be accrued for this study within 4 years.

Eligibility criteria: 1. Documentation of Disease:

   1.1 Diagnosis of Chronic Myelogenous Leukemia (CML) in chronic phase. Patients in either accelerated or blastic phases are not eligible. Clonal cytogenetic evolution alone does not exclude patients. See Appendix I for definitions of accelerated and blastic phases of CML.

   1.2 Patients in whom a Philadelphia chromosome \[t(9;22)\] is not detectable by cytogenetic studies are eligible if they meet one of the following criteria:
   * BCR/ABL protein detectable by immunoblotting
   * BCR/ABL rearrangement detectable by Southern blot analysis
   * Polymerase chain reaction (PCR) positive fusion transcripts for BCR/ABL
   * BCR/ABL translocation present by fluorescence in situ hybridization (FISH).
2. Prior Treatment:

   2.1 No previous therapy with homoharringtonine (HHT)

   2.2 No more than six months cumulative (\<180 days) of prior hydroxyurea (HU) therapy. However, patients may not have received more than 60 days of HU treatment after failing interferon. Patients with previous intolerance or failure to respond to HU are not eligible.

   2.3 Patients must have failed an adequate trial (5M units/m2/day) of alpha-Interferon (IFN) or IFN/ara-C to be eligible, as defined below (any ONE of the following):
   * Failure to achieve a complete hematologic response after 6 months of IFN therapy.
   * Failure to achieve any cytogenetic response (i.e., still 100% Ph+) after 12 months of IFN therapy.
   * Intolerable adverse effects of IFN therapy after at least one month of IFN treatment. Significant documented toxicity of ≥ grade 3 (using NCI Common Toxicity Criteria guidelines) due to IFN is required.
   * Loss of a prior hematologic remission or cytogenetic response to IFN.
   * A two-fold increase in WBC count when compared to WBC count when IFN therapy was initiated.
3. Age ≥ 16 years
4. Patients with uncontrolled tachyarrhythmias (such as, atrial fibrillation, paroxysmal supraventricular tachycardia, and ventricular tachycardias not adequately controlled) are not eligible.
5. Non-pregnant and non-nursing. Treatment under this protocol would expose an unborn child to significant risks. Women and men of reproductive potential should agree to use an effective means of birth control.

Primary outcomes:
measure: Overall survival
timeFrame: 4 years
Secondary outcomes:
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Veterans Affairs Medical Center - Birmingham
state: Alabama
city: Mobile
country: United States
facility: MBCCOP - University of South Alabama
state: Alabama
city: Phoenix
country: United States
facility: CCOP - Greater Phoenix
state: Arizona
city: Phoenix
country: United States
facility: Veterans Affairs Medical Center - Phoenix (Hayden)
state: Arizona
city: Tucson
country: United States
facility: Veterans Affairs Medical Center - Tucson
state: Arizona
city: Tucson
country: United States
facility: Arizona Cancer Center
state: Arizona
city: Little Rock
country: United States
facility: University of Arkansas for Medical Sciences
state: Arkansas
city: Little Rock
country: United States
facility: Veterans Affairs Medical Center - Little Rock (McClellan)
state: Arkansas
city: La Jolla
country: United States
facility: University of California San Diego Cancer Center
state: California
city: Long Beach
country: United States
facility: Veterans Affairs Medical Center - Long Beach
state: California
city: Los Angeles
country: United States
facility: USC/Norris Comprehensive Cancer Center
state: California
city: Los Angeles
country: United States
facility: Jonsson Comprehensive Cancer Center, UCLA
state: California
city: Los Angeles
country: United States
facility: Beckman Research Institute, City of Hope
state: California
city: Martinez
country: United States
facility: Veterans Affairs Outpatient Clinic - Martinez
state: California
city: Oakland
country: United States
facility: CCOP - Bay Area Tumor Institute
state: California
city: Orange
country: United States
facility: Chao Family Comprehensive Cancer Center
state: California
city: Sacramento
country: United States
facility: University of California Davis Medical Center
state: California
city: San Francisco
country: United States
facility: UCSF Cancer Center and Cancer Research Institute
state: California
city: San Francisco
country: United States
facility: Veterans Affairs Medical Center - San Francisco
state: California
city: Santa Rosa
country: United States
facility: CCOP - Santa Rosa Memorial Hospital
state: California
city: Travis Air Force Base
country: United States
facility: David Grant Medical Center
state: California
city: Denver
country: United States
facility: Veterans Affairs Medical Center - Denver
state: Colorado
city: Denver
country: United States
facility: University of Colorado Cancer Center
state: Colorado
city: Wilmington
country: United States
facility: CCOP - Christiana Care Health Services
state: Delaware
city: Washington
country: United States
facility: Lombardi Cancer Center, Georgetown University
state: District of Columbia
city: Washington
country: United States
facility: Walter Reed Army Medical Center
state: District of Columbia
city: Miami Beach
country: United States
facility: CCOP - Mount Sinai Medical Center
state: Florida
city: Atlanta
country: United States
facility: CCOP - Atlanta Regional
state: Georgia
city: Fort Gordon
country: United States
facility: Dwight David Eisenhower Army Medical Center
state: Georgia
city: Honolulu
country: United States
facility: Cancer Research Center of Hawaii
state: Hawaii
city: Chicago
country: United States
facility: University of Illinois at Chicago Health Sciences Center
state: Illinois
city: Chicago
country: United States
facility: Veterans Affairs Medical Center - Chicago (Westside Hospital)
state: Illinois
city: Chicago
country: United States
facility: University of Chicago Cancer Research Center
state: Illinois
city: Decatur
country: United States
facility: CCOP - Central Illinois
state: Illinois
city: Hines
country: United States
facility: Veterans Affairs Medical Center - Hines (Hines Junior VA Hospital)
state: Illinois
city: Maywood
country: United States
facility: Loyola University Medical Center
state: Illinois
city: Iowa City
country: United States
facility: University of Iowa Hospitals and Clinics
state: Iowa
city: Kansas City
country: United States
facility: University of Kansas Medical Center
state: Kansas
city: Wichita
country: United States
facility: CCOP - Wichita
state: Kansas
city: Wichita
country: United States
facility: Veterans Affairs Medical Center - Wichita
state: Kansas
city: Lexington
country: United States
facility: Veterans Affairs Medical Center - Lexington
state: Kentucky
city: Lexington
country: United States
facility: Albert B. Chandler Medical Center, University of Kentucky
state: Kentucky
city: New Orleans
country: United States
facility: MBCCOP - LSU Medical Center
state: Louisiana
city: New Orleans
country: United States
facility: Tulane University School of Medicine
state: Louisiana
city: New Orleans
country: United States
facility: Veterans Affairs Medical Center - New Orleans
state: Louisiana
city: Shreveport
country: United States
facility: Louisiana State University Health Sciences Center - Shreveport
state: Louisiana
city: Shreveport
country: United States
facility: Veterans Affairs Medical Center - Shreveport
state: Louisiana
city: Togus
country: United States
facility: Veterans Affairs Medical Center - Togus
state: Maine
city: Baltimore
country: United States
facility: Marlene & Stewart Greenebaum Cancer Center, University of Maryland
state: Maryland
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
city: Boston
country: United States
facility: Boston Medical Center
state: Massachusetts
city: Jamaica Plain
country: United States
facility: Veterans Affairs Medical Center - Boston (Jamaica Plain)
state: Massachusetts
city: Worcester
country: United States
facility: University of Massachusetts Memorial Medical Center
state: Massachusetts
city: Ann Arbor
country: United States
facility: Veterans Affairs Medical Center - Ann Arbor
state: Michigan
city: Ann Arbor
country: United States
facility: University of Michigan Comprehensive Cancer Center
state: Michigan
city: Detroit
country: United States
facility: Veterans Affairs Medical Center - Detroit
state: Michigan
city: Detroit
country: United States
facility: Barbara Ann Karmanos Cancer Institute
state: Michigan
city: Detroit
country: United States
facility: Henry Ford Hospital
state: Michigan
city: Grand Rapids
country: United States
facility: CCOP - Grand Rapids Clinical Oncology Program
state: Michigan
city: Southfield
country: United States
facility: Providence Hospital - Southfield
state: Michigan
city: Minneapolis
country: United States
facility: Veterans Affairs Medical Center - Minneapolis
state: Minnesota
city: Minneapolis
country: United States
facility: University of Minnesota Cancer Center
state: Minnesota
city: Biloxi
country: United States
facility: Veterans Affairs Medical Center - Biloxi
state: Mississippi
city: Jackson
country: United States
facility: University of Mississippi Medical Center
state: Mississippi
city: Jackson
country: United States
facility: Veterans Affairs Medical Center - Jackson
state: Mississippi
city: Keesler AFB
country: United States
facility: Keesler Medical Center - Keesler AFB
state: Mississippi
city: Columbia
country: United States
facility: Veterans Affairs Medical Center - Columbia (Truman Memorial)
state: Missouri
city: Columbia
country: United States
facility: Ellis Fischel Cancer Center - Columbia
state: Missouri
city: Kansas City
country: United States
facility: Veterans Affairs Medical Center - Kansas City
state: Missouri
city: Kansas City
country: United States
facility: CCOP - Kansas City
state: Missouri
city: Saint Louis
country: United States
facility: St. Louis University Health Sciences Center
state: Missouri
city: Saint Louis
country: United States
facility: Barnes-Jewish Hospital
state: Missouri
city: Saint Louis
country: United States
facility: CCOP - St. Louis-Cape Girardeau
state: Missouri
city: Springfield
country: United States
facility: CCOP - Cancer Research for the Ozarks
state: Missouri
city: Billings
country: United States
facility: CCOP - Montana Cancer Consortium
state: Montana
city: Omaha
country: United States
facility: University of Nebraska Medical Center
state: Nebraska
city: Las Vegas
country: United States
facility: CCOP - Southern Nevada Cancer Research Foundation
state: Nevada
city: Lebanon
country: United States
facility: Norris Cotton Cancer Center
state: New Hampshire
city: Albuquerque
country: United States
facility: Veterans Affairs Medical Center - Albuquerque
state: New Mexico
city: Albuquerque
country: United States
facility: MBCCOP - University of New Mexico HSC
state: New Mexico
city: Buffalo
country: United States
facility: Veterans Affairs Medical Center - Buffalo
state: New York
city: Buffalo
country: United States
facility: Roswell Park Cancer Institute
state: New York
city: Manhasset
country: United States
facility: CCOP - North Shore University Hospital
state: New York
city: Manhasset
country: United States
facility: North Shore University Hospital
state: New York
city: New York
country: United States
facility: Memorial Sloan-Kettering Cancer Center
state: New York
city: New York
country: United States
facility: New York Presbyterian Hospital - Cornell Campus
state: New York
city: New York
country: United States
facility: Mount Sinai Medical Center, NY
state: New York
city: New York
country: United States
facility: Herbert Irving Comprehensive Cancer Center
state: New York
city: Syracuse
country: United States
facility: State University of New York - Upstate Medical University
state: New York
city: Syracuse
country: United States
facility: Veterans Affairs Medical Center - Syracuse
state: New York
city: Syracuse
country: United States
facility: CCOP - Syracuse Hematology-Oncology Associates of Central New York, P.C.
state: New York
city: Chapel Hill
country: United States
facility: Lineberger Comprehensive Cancer Center, UNC
state: North Carolina
city: Durham
country: United States
facility: Veterans Affairs Medical Center - Durham
state: North Carolina
city: Durham
country: United States
facility: Duke Comprehensive Cancer Center
state: North Carolina
city: Winston-Salem
country: United States
facility: CCOP - Southeast Cancer Control Consortium
state: North Carolina
city: Winston-Salem
country: United States
facility: Comprehensive Cancer Center of Wake Forest University Baptist Medical Center
state: North Carolina
city: Cincinnati
country: United States
facility: Barrett Cancer Center, The University Hospital
state: Ohio
city: Cincinnati
country: United States
facility: Veterans Affairs Medical Center - Cincinnati
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic Taussig Cancer Center
state: Ohio
city: Columbus
country: United States
facility: CCOP - Columbus
state: Ohio
city: Columbus
country: United States
facility: Arthur G. James Cancer Hospital - Ohio State University
state: Ohio
city: Dayton
country: United States
facility: Veterans Affairs Medical Center - Dayton
state: Ohio
city: Kettering
country: United States
facility: CCOP - Dayton
state: Ohio
city: Oklahoma City
country: United States
facility: Oklahoma Medical Research Foundation
state: Oklahoma
city: Oklahoma City
country: United States
facility: Veterans Affairs Medical Center - Oklahoma City
state: Oklahoma
city: Portland
country: United States
facility: Oregon Cancer Center at Oregon Health Sciences University
state: Oregon
city: Portland
country: United States
facility: Veterans Affairs Medical Center - Portland
state: Oregon
city: Portland
country: United States
facility: CCOP - Columbia River Program
state: Oregon
city: Providence
country: United States
facility: Rhode Island Hospital
state: Rhode Island
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Greenville
country: United States
facility: CCOP - Greenville
state: South Carolina
city: Spartanburg
country: United States
facility: CCOP - Upstate Carolina
state: South Carolina
city: Memphis
country: United States
facility: University of Tennessee, Memphis Cancer Center
state: Tennessee
city: Memphis
country: United States
facility: Veterans Affairs Medical Center - Memphis
state: Tennessee
city: Dallas
country: United States
facility: Simmons Cancer Center - Dallas
state: Texas
city: Fort Sam Houston
country: United States
facility: Brooke Army Medical Center
state: Texas
city: Galveston
country: United States
facility: University of Texas Medical Branch
state: Texas
city: Lubbock
country: United States
facility: Texas Tech University Health Science Center
state: Texas
city: San Antonio
country: United States
facility: University of Texas Health Science Center at San Antonio
state: Texas
city: San Antonio
country: United States
facility: Veterans Affairs Medical Center - San Antonio (Murphy)
state: Texas
city: Temple
country: United States
facility: Veterans Affairs Medical Center - Temple
state: Texas
city: Temple
country: United States
facility: CCOP - Scott and White Hospital
state: Texas
city: Salt Lake City
country: United States
facility: Huntsman Cancer Institute
state: Utah
city: Salt Lake City
country: United States
facility: Veterans Affairs Medical Center - Salt Lake City
state: Utah
city: Bennington
country: United States
facility: CCOP - Southwestern Vermont Regional Cancer Center
state: Vermont
city: Burlington
country: United States
facility: Vermont Cancer Center
state: Vermont
city: White River Junction
country: United States
facility: Veterans Affairs Medical Center - White River Junction
state: Vermont
city: Richmond
country: United States
facility: Veterans Affairs Medical Center - Richmond
state: Virginia
city: Richmond
country: United States
facility: MBCCOP - Massey Cancer Center
state: Virginia
city: Seattle
country: United States
facility: CCOP - Virginia Mason Research Center
state: Washington
city: Seattle
country: United States
facility: Swedish Cancer Institute
state: Washington
city: Seattle
country: United States
facility: Veterans Affairs Medical Center - Seattle
state: Washington
city: Tacoma
country: United States
facility: CCOP - Northwest
state: Washington
Study officials:
affiliation: Dana-Farber Cancer Institute
name: Dan DeAngelo, MD
role: STUDY_CHAIR
References: