- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00004933
Homoharringtonine Compared With Hydroxyurea for Chronic Myelogenous Leukemia That Has Not Responded to Interferon Alfa
A Phase III Study of Interferon-Refractory Patients With BCR/ABL(+) Chronic Myelogenous Leukemia (CML) Treated With Homoharringtonine (NSC #141633) vs. Hydroxyurea
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.
Study Overview
Status
Conditions
Intervention / Treatment
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.
Study Type
Enrollment (Actual)
Phase
- Phase 3
Contacts and Locations
Study Locations
-
-
Alabama
-
Birmingham, Alabama, United States, 35233
- Veterans Affairs Medical Center - Birmingham
-
Mobile, Alabama, United States, 36688
- MBCCOP - University of South Alabama
-
-
Arizona
-
Phoenix, Arizona, United States, 85006-2726
- CCOP - Greater Phoenix
-
Phoenix, Arizona, United States, 85012
- Veterans Affairs Medical Center - Phoenix (Hayden)
-
Tucson, Arizona, United States, 85724
- Arizona Cancer Center
-
Tucson, Arizona, United States, 85723
- Veterans Affairs Medical Center - Tucson
-
-
Arkansas
-
Little Rock, Arkansas, United States, 72205
- University of Arkansas for Medical Sciences
-
Little Rock, Arkansas, United States, 72205
- Veterans Affairs Medical Center - Little Rock (McClellan)
-
-
California
-
La Jolla, California, United States, 92093-0658
- University of California San Diego Cancer Center
-
Long Beach, California, United States, 90822
- Veterans Affairs Medical Center - Long Beach
-
Los Angeles, California, United States, 90033-0800
- USC/Norris Comprehensive Cancer Center
-
Los Angeles, California, United States, 90095-1781
- Jonsson Comprehensive Cancer Center, UCLA
-
Los Angeles, California, United States, 91010
- Beckman Research Institute, City of Hope
-
Martinez, California, United States, 94553
- Veterans Affairs Outpatient Clinic - Martinez
-
Oakland, California, United States, 94609-3305
- CCOP - Bay Area Tumor Institute
-
Orange, California, United States, 92868
- Chao Family Comprehensive Cancer Center
-
Sacramento, California, United States, 95817
- University of California Davis Medical Center
-
San Francisco, California, United States, 94121
- Veterans Affairs Medical Center - San Francisco
-
San Francisco, California, United States, 94115-0128
- UCSF Cancer Center and Cancer Research Institute
-
Santa Rosa, California, United States, 95403
- CCOP - Santa Rosa Memorial Hospital
-
Travis Air Force Base, California, United States, 94535
- David Grant Medical Center
-
-
Colorado
-
Denver, Colorado, United States, 80220
- Veterans Affairs Medical Center - Denver
-
Denver, Colorado, United States, 80262
- University of Colorado Cancer Center
-
-
Delaware
-
Wilmington, Delaware, United States, 19899
- CCOP - Christiana Care Health Services
-
-
District of Columbia
-
Washington, District of Columbia, United States, 20307-5000
- Walter Reed Army Medical Center
-
Washington, District of Columbia, United States, 20007
- Lombardi Cancer Center, Georgetown University
-
-
Florida
-
Miami Beach, Florida, United States, 33140
- CCOP - Mount Sinai Medical Center
-
-
Georgia
-
Atlanta, Georgia, United States, 30342-1701
- CCOP - Atlanta Regional
-
Fort Gordon, Georgia, United States, 30905-5650
- Dwight David Eisenhower Army Medical Center
-
-
Hawaii
-
Honolulu, Hawaii, United States, 96813
- Cancer Research Center of Hawaii
-
-
Illinois
-
Chicago, Illinois, United States, 60612
- Veterans Affairs Medical Center - Chicago (Westside Hospital)
-
Chicago, Illinois, United States, 60637
- University of Chicago Cancer Research Center
-
Chicago, Illinois, United States, 60612
- University of Illinois at Chicago Health Sciences Center
-
Decatur, Illinois, United States, 62526
- CCOP - Central Illinois
-
Hines, Illinois, United States, 60141
- Veterans Affairs Medical Center - Hines (Hines Junior VA Hospital)
-
Maywood, Illinois, United States, 60153
- Loyola University Medical Center
-
-
Iowa
-
Iowa City, Iowa, United States, 52242
- University of Iowa Hospitals and Clinics
-
-
Kansas
-
Kansas City, Kansas, United States, 66160-7357
- University of Kansas Medical Center
-
Wichita, Kansas, United States, 67214-3882
- CCOP - Wichita
-
Wichita, Kansas, United States, 67218
- Veterans Affairs Medical Center - Wichita
-
-
Kentucky
-
Lexington, Kentucky, United States, 40511-1093
- Veterans Affairs Medical Center - Lexington
-
Lexington, Kentucky, United States, 40536-0084
- Albert B. Chandler Medical Center, University of Kentucky
-
-
Louisiana
-
New Orleans, Louisiana, United States, 70112
- Tulane University School of Medicine
-
New Orleans, Louisiana, United States, 70112
- MBCCOP - LSU Medical Center
-
New Orleans, Louisiana, United States, 70112
- Veterans Affairs Medical Center - New Orleans
-
Shreveport, Louisiana, United States, 71130-3932
- Louisiana State University Health Sciences Center - Shreveport
-
Shreveport, Louisiana, United States, 71130
- Veterans Affairs Medical Center - Shreveport
-
-
Maine
-
Togus, Maine, United States, 04330
- Veterans Affairs Medical Center - Togus
-
-
Maryland
-
Baltimore, Maryland, United States, 21201
- Marlene & Stewart Greenebaum Cancer Center, University of Maryland
-
-
Massachusetts
-
Boston, Massachusetts, United States, 02115
- Dana-Farber Cancer Institute
-
Boston, Massachusetts, United States, 02118
- Boston Medical Center
-
Jamaica Plain, Massachusetts, United States, 02130
- Veterans Affairs Medical Center - Boston (Jamaica Plain)
-
Worcester, Massachusetts, United States, 01655
- University of Massachusetts Memorial Medical Center
-
-
Michigan
-
Ann Arbor, Michigan, United States, 48109-0752
- University of Michigan Comprehensive Cancer Center
-
Ann Arbor, Michigan, United States, 48105
- Veterans Affairs Medical Center - Ann Arbor
-
Detroit, Michigan, United States, 48201
- Barbara Ann Karmanos Cancer Institute
-
Detroit, Michigan, United States, 48202
- Henry Ford Hospital
-
Detroit, Michigan, United States, 48201-1932
- Veterans Affairs Medical Center - Detroit
-
Grand Rapids, Michigan, United States, 49503
- CCOP - Grand Rapids Clinical Oncology Program
-
Southfield, Michigan, United States, 48075-9975
- Providence Hospital - Southfield
-
-
Minnesota
-
Minneapolis, Minnesota, United States, 55417
- Veterans Affairs Medical Center - Minneapolis
-
Minneapolis, Minnesota, United States, 55455
- University of Minnesota Cancer Center
-
-
Mississippi
-
Biloxi, Mississippi, United States, 39531-2410
- Veterans Affairs Medical Center - Biloxi
-
Jackson, Mississippi, United States, 39216-4505
- University of Mississippi Medical Center
-
Jackson, Mississippi, United States, 39216
- Veterans Affairs Medical Center - Jackson
-
Keesler AFB, Mississippi, United States, 39534-2576
- Keesler Medical Center - Keesler AFB
-
-
Missouri
-
Columbia, Missouri, United States, 65201
- Veterans Affairs Medical Center - Columbia (Truman Memorial)
-
Columbia, Missouri, United States, 65203
- Ellis Fischel Cancer Center - Columbia
-
Kansas City, Missouri, United States, 64128
- Veterans Affairs Medical Center - Kansas City
-
Kansas City, Missouri, United States, 64131
- CCOP - Kansas City
-
Saint Louis, Missouri, United States, 63110
- Barnes-Jewish Hospital
-
Saint Louis, Missouri, United States, 63110-0250
- St. Louis University Health Sciences Center
-
Saint Louis, Missouri, United States, 63141
- CCOP - St. Louis-Cape Girardeau
-
Springfield, Missouri, United States, 65807
- CCOP - Cancer Research for the Ozarks
-
-
Montana
-
Billings, Montana, United States, 59101
- CCOP - Montana Cancer Consortium
-
-
Nebraska
-
Omaha, Nebraska, United States, 68198-3330
- University of Nebraska Medical Center
-
-
Nevada
-
Las Vegas, Nevada, United States, 89106
- CCOP - Southern Nevada Cancer Research Foundation
-
-
New Hampshire
-
Lebanon, New Hampshire, United States, 03756
- Norris Cotton Cancer Center
-
-
New Mexico
-
Albuquerque, New Mexico, United States, 87108-5138
- Veterans Affairs Medical Center - Albuquerque
-
Albuquerque, New Mexico, United States, 87131
- MBCCOP - University of New Mexico HSC
-
-
New York
-
Buffalo, New York, United States, 14263-0001
- Roswell Park Cancer Institute
-
Buffalo, New York, United States, 14215
- Veterans Affairs Medical Center - Buffalo
-
Manhasset, New York, United States, 11030
- CCOP - North Shore University Hospital
-
Manhasset, New York, United States, 11030
- North Shore University Hospital
-
New York, New York, United States, 10021
- Memorial Sloan-Kettering Cancer Center
-
New York, New York, United States, 10021
- New York Presbyterian Hospital - Cornell Campus
-
New York, New York, United States, 10029
- Mount Sinai Medical Center, NY
-
New York, New York, United States, 10032
- Herbert Irving Comprehensive Cancer Center
-
Syracuse, New York, United States, 13210
- State University of New York - Upstate Medical University
-
Syracuse, New York, United States, 13210
- Veterans Affairs Medical Center - Syracuse
-
Syracuse, New York, United States, 13217
- CCOP - Syracuse Hematology-Oncology Associates of Central New York, P.C.
-
-
North Carolina
-
Chapel Hill, North Carolina, United States, 27599-7295
- Lineberger Comprehensive Cancer Center, UNC
-
Durham, North Carolina, United States, 27705
- Veterans Affairs Medical Center - Durham
-
Durham, North Carolina, United States, 27710
- Duke Comprehensive Cancer Center
-
Winston-Salem, North Carolina, United States, 27104-4241
- CCOP - Southeast Cancer Control Consortium
-
Winston-Salem, North Carolina, United States, 27157-1082
- Comprehensive Cancer Center of Wake Forest University Baptist Medical Center
-
-
Ohio
-
Cincinnati, Ohio, United States, 45219
- Barrett Cancer Center, The University Hospital
-
Cincinnati, Ohio, United States, 45220-2288
- Veterans Affairs Medical Center - Cincinnati
-
Cleveland, Ohio, United States, 44195
- Cleveland Clinic Taussig Cancer Center
-
Columbus, Ohio, United States, 43206
- CCOP - Columbus
-
Columbus, Ohio, United States, 43210
- Arthur G. James Cancer Hospital - Ohio State University
-
Dayton, Ohio, United States, 45428
- Veterans Affairs Medical Center - Dayton
-
Kettering, Ohio, United States, 45429
- CCOP - Dayton
-
-
Oklahoma
-
Oklahoma City, Oklahoma, United States, 73104
- Oklahoma Medical Research Foundation
-
Oklahoma City, Oklahoma, United States, 73104
- Veterans Affairs Medical Center - Oklahoma City
-
-
Oregon
-
Portland, Oregon, United States, 97201-3098
- Oregon Cancer Center at Oregon Health Sciences University
-
Portland, Oregon, United States, 97207
- Veterans Affairs Medical Center - Portland
-
Portland, Oregon, United States, 97213
- CCOP - Columbia River Program
-
-
Rhode Island
-
Providence, Rhode Island, United States, 02903
- Rhode Island Hospital
-
-
South Carolina
-
Charleston, South Carolina, United States, 29425-0721
- Medical University of South Carolina
-
Greenville, South Carolina, United States, 29615
- CCOP - Greenville
-
Spartanburg, South Carolina, United States, 29303
- CCOP - Upstate Carolina
-
-
Tennessee
-
Memphis, Tennessee, United States, 38103
- University of Tennessee, Memphis Cancer Center
-
Memphis, Tennessee, United States, 38104
- Veterans Affairs Medical Center - Memphis
-
-
Texas
-
Dallas, Texas, United States, 75235-9154
- Simmons Cancer Center - Dallas
-
Fort Sam Houston, Texas, United States, 78234
- Brooke Army Medical Center
-
Galveston, Texas, United States, 77555-0209
- University of Texas Medical Branch
-
Lubbock, Texas, United States, 79423
- Texas Tech University Health Science Center
-
San Antonio, Texas, United States, 78284-7811
- University of Texas Health Science Center at San Antonio
-
San Antonio, Texas, United States, 78284
- Veterans Affairs Medical Center - San Antonio (Murphy)
-
Temple, Texas, United States, 76504
- Veterans Affairs Medical Center - Temple
-
Temple, Texas, United States, 76508
- CCOP - Scott and White Hospital
-
-
Utah
-
Salt Lake City, Utah, United States, 84132
- Huntsman Cancer Institute
-
Salt Lake City, Utah, United States, 84148
- Veterans Affairs Medical Center - Salt Lake City
-
-
Vermont
-
Bennington, Vermont, United States, 05201
- CCOP - Southwestern Vermont Regional Cancer Center
-
Burlington, Vermont, United States, 05401-3498
- Vermont Cancer Center
-
White River Junction, Vermont, United States, 05009
- Veterans Affairs Medical Center - White River Junction
-
-
Virginia
-
Richmond, Virginia, United States, 23298-0037
- MBCCOP - Massey Cancer Center
-
Richmond, Virginia, United States, 23249
- Veterans Affairs Medical Center - Richmond
-
-
Washington
-
Seattle, Washington, United States, 98101
- CCOP - Virginia Mason Research Center
-
Seattle, Washington, United States, 98104
- Swedish Cancer Institute
-
Seattle, Washington, United States, 98108
- Veterans Affairs Medical Center - Seattle
-
Tacoma, Washington, United States, 98405-0986
- CCOP - Northwest
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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).
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.
- Age ≥ 16 years
- Patients with uncontrolled tachyarrhythmias (such as, atrial fibrillation, paroxysmal supraventricular tachycardia, and ventricular tachycardias not adequately controlled) are not eligible.
- 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.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: RANDOMIZED
- Interventional Model: PARALLEL
- Masking: NONE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
EXPERIMENTAL: Homoharringtonine
|
2.5 mg/ sq m/ day CIVI for 14 days
|
ACTIVE_COMPARATOR: Hydroxyurea
|
0.5 to 5 grams PO per day
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Overall survival
Time Frame: 4 years
|
4 years
|
Collaborators and Investigators
Collaborators
Investigators
- Study Chair: Dan DeAngelo, MD, Dana-Farber Cancer Institute
Study record dates
Study Major Dates
Study Start
Primary Completion (ACTUAL)
Study Completion (ACTUAL)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ESTIMATE)
Study Record Updates
Last Update Posted (ESTIMATE)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Neoplasms by Histologic Type
- Neoplasms
- Bone Marrow Diseases
- Hematologic Diseases
- Myeloproliferative Disorders
- Leukemia
- Leukemia, Myeloid
- Leukemia, Myelogenous, Chronic, BCR-ABL Positive
- Molecular Mechanisms of Pharmacological Action
- Nucleic Acid Synthesis Inhibitors
- Enzyme Inhibitors
- Antineoplastic Agents
- Antineoplastic Agents, Phytogenic
- Protein Synthesis Inhibitors
- Antisickling Agents
- Hydroxyurea
- Homoharringtonine
Other Study ID Numbers
- CALGB-19807
- U10CA031946 (U.S. NIH Grant/Contract)
- CDR0000067617 (REGISTRY: NCI Physician Data Query)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Leukemia
-
Stanford UniversityTerminatedLeukemia | Leukemia, Lymphocytic, Acute | Leukemia Acute Promyelocytic Leukemia (APL) | Leukemia Acute Lymphoid Leukemia (ALL) | Leukemia Chronic Myelogenous Leukemia (CML) | Leukemia Acute Myeloid Leukemia (AML) | Leukemia Chronic Lymphocytic Leukemia (CLL)United States
-
Massachusetts General HospitalCelgene CorporationTerminatedAcute Myelogenous Leukemia | Acute Myeloid Leukemia (AML) | Acute Myelocytic Leukemia | Acute Granulocytic Leukemia | Acute Non-Lymphocytic LeukemiaUnited States
-
Children's Oncology GroupNational Cancer Institute (NCI)CompletedChildhood Acute Monoblastic Leukemia (M5a) | Childhood Acute Monocytic Leukemia (M5b) | Childhood Acute Myeloblastic Leukemia Without Maturation (M1) | Childhood Acute Myelomonocytic Leukemia (M4) | Childhood Acute Myeloid Leukemia/Other Myeloid MalignanciesUnited States
-
Institute of Hematology & Blood Diseases HospitalBejing Institute for Stem Cell and Regenerative Medicine; Institute for Stem...RecruitingRefractory Leukemia | Relapsed Leukemia | Acute Myeloid Leukemia, ChildhoodChina
-
Hybrigenics CorporationUnknownAcute Myelogenous LeukemiaUnited States, France
-
Betta Pharmaceuticals Co., Ltd.Not yet recruitingAcute Myeloid Leukemia LeukemiaChina
-
Beijing Boren HospitalRecruitingAcute Myeloid Leukemia | Refractory Acute Myeloid Leukemia | Relapse LeukemiaChina
-
Center for International Blood and Marrow Transplant...National Marrow Donor Program; St. Baldrick's FoundationActive, not recruitingAcute Myelogenous LeukemiaUnited States
-
Massachusetts General HospitalCompleted
-
Kinex Pharmaceuticals Inc.CompletedAcute Myelogenous LeukemiaUnited States
Clinical Trials on Homoharringtonine
-
National Cancer Institute (NCI)WithdrawnLeukemiaUnited States
-
Air Force Military Medical University, ChinaThe Second Hospital of Hebei Medical University; Qilu Hospital of Shandong... and other collaboratorsRecruiting
-
The University of Hong KongCompletedAML | FLT3-ITD MutationHong Kong
-
The University of Hong KongUnknownAML | FLT3-ITD MutationHong Kong
-
National Cancer Institute (NCI)CompletedChildhood Chronic Myelogenous Leukemia | Chronic Phase Chronic Myelogenous Leukemia | Relapsing Chronic Myelogenous Leukemia | Chronic Myelogenous Leukemia, BCR-ABL1 PositiveUnited States
-
The First Affiliated Hospital with Nanjing Medical...RecruitingSecondary Acute Myeloid LeukemiaChina
-
First Affiliated Hospital of Zhejiang UniversityRecruitingAcute Myeloid Leukemia, AdultChina
-
Nanfang Hospital of Southern Medical UniversityThe Affiliated Hospital of Qingdao University; Sun Yat-Sen Memorial Hospital... and other collaboratorsRecruitingVenetoclax Combined With Azacitidine Plus Homoharringtonine | Venetoclax Combined With AzacitidineChina
-
ChemGenex PharmaceuticalsCompleted
-
M.D. Anderson Cancer CenterRecruitingHematopoietic and Lymphoid Cell Neoplasm | Recurrent Acute Myeloid Leukemia | Recurrent Myelodysplastic Syndrome | Refractory Acute Myeloid Leukemia | Refractory Myelodysplastic Syndrome | Recurrent Acute Biphenotypic Leukemia | Refractory Acute Biphenotypic LeukemiaUnited States