Homoharringtonine Compared With Hydroxyurea for Chronic Myelogenous Leukemia That Has Not Responded to Interferon Alfa

Sponsor

Alliance for Clinical Trials in Oncology (Other)

Overall Status

Terminated

CT.gov ID

NCT00004933

Collaborator

National Cancer Institute (NCI) (NIH)

Enrollment

133

Locations

Arms

Duration (Months)

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Leukemia	Drug: hydroxyurea Drug: Homoharringtonine	Phase 3

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 Design

Study Type:

Interventional

Actual Enrollment :

5 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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 Start Date :

Jan 1, 2000

Actual Primary Completion Date :

May 1, 2001

Actual Study Completion Date :

May 1, 2001

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Homoharringtonine	Drug: Homoharringtonine 2.5 mg/ sq m/ day CIVI for 14 days
Active Comparator: Hydroxyurea	Drug: hydroxyurea 0.5 to 5 grams PO per day

Arm

Intervention/Treatment

Experimental: Homoharringtonine

Drug: Homoharringtonine

2.5 mg/ sq m/ day CIVI for 14 days

Active Comparator: Hydroxyurea

Drug: hydroxyurea

0.5 to 5 grams PO per day

Outcome Measures

Primary Outcome Measures

Overall survival [4 years]

Eligibility Criteria

Criteria

Ages Eligible for Study:

16 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Veterans Affairs Medical Center - Birmingham	Birmingham	Alabama	United States	35233
2	MBCCOP - University of South Alabama	Mobile	Alabama	United States	36688
3	CCOP - Greater Phoenix	Phoenix	Arizona	United States	85006-2726
4	Veterans Affairs Medical Center - Phoenix (Hayden)	Phoenix	Arizona	United States	85012
5	Veterans Affairs Medical Center - Tucson	Tucson	Arizona	United States	85723
6	Arizona Cancer Center	Tucson	Arizona	United States	85724
7	University of Arkansas for Medical Sciences	Little Rock	Arkansas	United States	72205
8	Veterans Affairs Medical Center - Little Rock (McClellan)	Little Rock	Arkansas	United States	72205
9	University of California San Diego Cancer Center	La Jolla	California	United States	92093-0658
10	Veterans Affairs Medical Center - Long Beach	Long Beach	California	United States	90822
11	USC/Norris Comprehensive Cancer Center	Los Angeles	California	United States	90033-0800
12	Jonsson Comprehensive Cancer Center, UCLA	Los Angeles	California	United States	90095-1781
13	Beckman Research Institute, City of Hope	Los Angeles	California	United States	91010
14	Veterans Affairs Outpatient Clinic - Martinez	Martinez	California	United States	94553
15	CCOP - Bay Area Tumor Institute	Oakland	California	United States	94609-3305
16	Chao Family Comprehensive Cancer Center	Orange	California	United States	92868
17	University of California Davis Medical Center	Sacramento	California	United States	95817
18	UCSF Cancer Center and Cancer Research Institute	San Francisco	California	United States	94115-0128
19	Veterans Affairs Medical Center - San Francisco	San Francisco	California	United States	94121
20	CCOP - Santa Rosa Memorial Hospital	Santa Rosa	California	United States	95403
21	David Grant Medical Center	Travis Air Force Base	California	United States	94535
22	Veterans Affairs Medical Center - Denver	Denver	Colorado	United States	80220
23	University of Colorado Cancer Center	Denver	Colorado	United States	80262
24	CCOP - Christiana Care Health Services	Wilmington	Delaware	United States	19899
25	Lombardi Cancer Center, Georgetown University	Washington	District of Columbia	United States	20007
26	Walter Reed Army Medical Center	Washington	District of Columbia	United States	20307-5000
27	CCOP - Mount Sinai Medical Center	Miami Beach	Florida	United States	33140
28	CCOP - Atlanta Regional	Atlanta	Georgia	United States	30342-1701
29	Dwight David Eisenhower Army Medical Center	Fort Gordon	Georgia	United States	30905-5650
30	Cancer Research Center of Hawaii	Honolulu	Hawaii	United States	96813
31	University of Illinois at Chicago Health Sciences Center	Chicago	Illinois	United States	60612
32	Veterans Affairs Medical Center - Chicago (Westside Hospital)	Chicago	Illinois	United States	60612
33	University of Chicago Cancer Research Center	Chicago	Illinois	United States	60637
34	CCOP - Central Illinois	Decatur	Illinois	United States	62526
35	Veterans Affairs Medical Center - Hines (Hines Junior VA Hospital)	Hines	Illinois	United States	60141
36	Loyola University Medical Center	Maywood	Illinois	United States	60153
37	University of Iowa Hospitals and Clinics	Iowa City	Iowa	United States	52242
38	University of Kansas Medical Center	Kansas City	Kansas	United States	66160-7357
39	CCOP - Wichita	Wichita	Kansas	United States	67214-3882
40	Veterans Affairs Medical Center - Wichita	Wichita	Kansas	United States	67218
41	Veterans Affairs Medical Center - Lexington	Lexington	Kentucky	United States	40511-1093
42	Albert B. Chandler Medical Center, University of Kentucky	Lexington	Kentucky	United States	40536-0084
43	MBCCOP - LSU Medical Center	New Orleans	Louisiana	United States	70112
44	Tulane University School of Medicine	New Orleans	Louisiana	United States	70112
45	Veterans Affairs Medical Center - New Orleans	New Orleans	Louisiana	United States	70112
46	Louisiana State University Health Sciences Center - Shreveport	Shreveport	Louisiana	United States	71130-3932
47	Veterans Affairs Medical Center - Shreveport	Shreveport	Louisiana	United States	71130
48	Veterans Affairs Medical Center - Togus	Togus	Maine	United States	04330
49	Marlene & Stewart Greenebaum Cancer Center, University of Maryland	Baltimore	Maryland	United States	21201
50	Dana-Farber Cancer Institute	Boston	Massachusetts	United States	02115
51	Boston Medical Center	Boston	Massachusetts	United States	02118
52	Veterans Affairs Medical Center - Boston (Jamaica Plain)	Jamaica Plain	Massachusetts	United States	02130
53	University of Massachusetts Memorial Medical Center	Worcester	Massachusetts	United States	01655
54	Veterans Affairs Medical Center - Ann Arbor	Ann Arbor	Michigan	United States	48105
55	University of Michigan Comprehensive Cancer Center	Ann Arbor	Michigan	United States	48109-0752
56	Veterans Affairs Medical Center - Detroit	Detroit	Michigan	United States	48201-1932
57	Barbara Ann Karmanos Cancer Institute	Detroit	Michigan	United States	48201
58	Henry Ford Hospital	Detroit	Michigan	United States	48202
59	CCOP - Grand Rapids Clinical Oncology Program	Grand Rapids	Michigan	United States	49503
60	Providence Hospital - Southfield	Southfield	Michigan	United States	48075-9975
61	Veterans Affairs Medical Center - Minneapolis	Minneapolis	Minnesota	United States	55417
62	University of Minnesota Cancer Center	Minneapolis	Minnesota	United States	55455
63	Veterans Affairs Medical Center - Biloxi	Biloxi	Mississippi	United States	39531-2410
64	University of Mississippi Medical Center	Jackson	Mississippi	United States	39216-4505
65	Veterans Affairs Medical Center - Jackson	Jackson	Mississippi	United States	39216
66	Keesler Medical Center - Keesler AFB	Keesler AFB	Mississippi	United States	39534-2576
67	Veterans Affairs Medical Center - Columbia (Truman Memorial)	Columbia	Missouri	United States	65201
68	Ellis Fischel Cancer Center - Columbia	Columbia	Missouri	United States	65203
69	Veterans Affairs Medical Center - Kansas City	Kansas City	Missouri	United States	64128
70	CCOP - Kansas City	Kansas City	Missouri	United States	64131
71	St. Louis University Health Sciences Center	Saint Louis	Missouri	United States	63110-0250
72	Barnes-Jewish Hospital	Saint Louis	Missouri	United States	63110
73	CCOP - St. Louis-Cape Girardeau	Saint Louis	Missouri	United States	63141
74	CCOP - Cancer Research for the Ozarks	Springfield	Missouri	United States	65807
75	CCOP - Montana Cancer Consortium	Billings	Montana	United States	59101
76	University of Nebraska Medical Center	Omaha	Nebraska	United States	68198-3330
77	CCOP - Southern Nevada Cancer Research Foundation	Las Vegas	Nevada	United States	89106
78	Norris Cotton Cancer Center	Lebanon	New Hampshire	United States	03756
79	Veterans Affairs Medical Center - Albuquerque	Albuquerque	New Mexico	United States	87108-5138
80	MBCCOP - University of New Mexico HSC	Albuquerque	New Mexico	United States	87131
81	Veterans Affairs Medical Center - Buffalo	Buffalo	New York	United States	14215
82	Roswell Park Cancer Institute	Buffalo	New York	United States	14263-0001
83	CCOP - North Shore University Hospital	Manhasset	New York	United States	11030
84	North Shore University Hospital	Manhasset	New York	United States	11030
85	Memorial Sloan-Kettering Cancer Center	New York	New York	United States	10021
86	New York Presbyterian Hospital - Cornell Campus	New York	New York	United States	10021
87	Mount Sinai Medical Center, NY	New York	New York	United States	10029
88	Herbert Irving Comprehensive Cancer Center	New York	New York	United States	10032
89	State University of New York - Upstate Medical University	Syracuse	New York	United States	13210
90	Veterans Affairs Medical Center - Syracuse	Syracuse	New York	United States	13210
91	CCOP - Syracuse Hematology-Oncology Associates of Central New York, P.C.	Syracuse	New York	United States	13217
92	Lineberger Comprehensive Cancer Center, UNC	Chapel Hill	North Carolina	United States	27599-7295
93	Veterans Affairs Medical Center - Durham	Durham	North Carolina	United States	27705
94	Duke Comprehensive Cancer Center	Durham	North Carolina	United States	27710
95	CCOP - Southeast Cancer Control Consortium	Winston-Salem	North Carolina	United States	27104-4241
96	Comprehensive Cancer Center of Wake Forest University Baptist Medical Center	Winston-Salem	North Carolina	United States	27157-1082
97	Barrett Cancer Center, The University Hospital	Cincinnati	Ohio	United States	45219
98	Veterans Affairs Medical Center - Cincinnati	Cincinnati	Ohio	United States	45220-2288
99	Cleveland Clinic Taussig Cancer Center	Cleveland	Ohio	United States	44195
100	CCOP - Columbus	Columbus	Ohio	United States	43206
101	Arthur G. James Cancer Hospital - Ohio State University	Columbus	Ohio	United States	43210
102	Veterans Affairs Medical Center - Dayton	Dayton	Ohio	United States	45428
103	CCOP - Dayton	Kettering	Ohio	United States	45429
104	Oklahoma Medical Research Foundation	Oklahoma City	Oklahoma	United States	73104
105	Veterans Affairs Medical Center - Oklahoma City	Oklahoma City	Oklahoma	United States	73104
106	Oregon Cancer Center at Oregon Health Sciences University	Portland	Oregon	United States	97201-3098
107	Veterans Affairs Medical Center - Portland	Portland	Oregon	United States	97207
108	CCOP - Columbia River Program	Portland	Oregon	United States	97213
109	Rhode Island Hospital	Providence	Rhode Island	United States	02903
110	Medical University of South Carolina	Charleston	South Carolina	United States	29425-0721
111	CCOP - Greenville	Greenville	South Carolina	United States	29615
112	CCOP - Upstate Carolina	Spartanburg	South Carolina	United States	29303
113	University of Tennessee, Memphis Cancer Center	Memphis	Tennessee	United States	38103
114	Veterans Affairs Medical Center - Memphis	Memphis	Tennessee	United States	38104
115	Simmons Cancer Center - Dallas	Dallas	Texas	United States	75235-9154
116	Brooke Army Medical Center	Fort Sam Houston	Texas	United States	78234
117	University of Texas Medical Branch	Galveston	Texas	United States	77555-0209
118	Texas Tech University Health Science Center	Lubbock	Texas	United States	79423
119	University of Texas Health Science Center at San Antonio	San Antonio	Texas	United States	78284-7811
120	Veterans Affairs Medical Center - San Antonio (Murphy)	San Antonio	Texas	United States	78284
121	Veterans Affairs Medical Center - Temple	Temple	Texas	United States	76504
122	CCOP - Scott and White Hospital	Temple	Texas	United States	76508
123	Huntsman Cancer Institute	Salt Lake City	Utah	United States	84132
124	Veterans Affairs Medical Center - Salt Lake City	Salt Lake City	Utah	United States	84148
125	CCOP - Southwestern Vermont Regional Cancer Center	Bennington	Vermont	United States	05201
126	Vermont Cancer Center	Burlington	Vermont	United States	05401-3498
127	Veterans Affairs Medical Center - White River Junction	White River Junction	Vermont	United States	05009
128	Veterans Affairs Medical Center - Richmond	Richmond	Virginia	United States	23249
129	MBCCOP - Massey Cancer Center	Richmond	Virginia	United States	23298-0037
130	CCOP - Virginia Mason Research Center	Seattle	Washington	United States	98101
131	Swedish Cancer Institute	Seattle	Washington	United States	98104
132	Veterans Affairs Medical Center - Seattle	Seattle	Washington	United States	98108
133	CCOP - Northwest	Tacoma	Washington	United States	98405-0986