SWOG-9400 Combination Chemotherapy With or Without Bone Marrow Transplantation in Treating Patients With Previously Untreated Acute Lymphocytic Leukemia

Sponsor

Southwest Oncology Group (Other)

Overall Status

Completed

CT.gov ID

NCT00002665

Collaborator

National Cancer Institute (NCI) (NIH)

Enrollment

Locations

101

Duration (Months)

0.6

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. Combining chemotherapy with bone marrow transplantation may allow the doctor to give higher doses of chemotherapy drugs and kill more cancer cells.

PURPOSE: Phase II trial to study the effectiveness of combination chemotherapy with or without bone marrow transplantation in treating patients who have acute lymphocytic leukemia.

Condition or Disease	Intervention/Treatment	Phase
Leukemia Neutropenia Thrombocytopenia	Drug: asparaginase Drug: cyclophosphamide Drug: cytarabine Drug: daunorubicin hydrochloride Drug: dexamethasone Drug: doxorubicin hydrochloride Drug: etoposide Drug: leucovorin calcium Drug: mercaptopurine Drug: methotrexate Drug: prednisone Drug: thioguanine Drug: vincristine sulfate Procedure: allogeneic bone marrow transplantation Radiation: radiation therapy	Phase 2

Detailed Description

OBJECTIVES: I. Evaluate if front line induction therapy with daunorubicin, vincristine, prednisone, and asparaginase is sufficiently effective to warrant a phase III trial in patients with acute lymphocytic leukemia (ALL). II. Assess the toxicity of this regimen in this patient population. III. Assess disease free and overall survival and toxicity associated with allogeneic bone marrow transplantation for ALL patients in first remission following induction and consolidation therapy. IV. Assess disease free and overall survival and toxicity associated with sequential regimens of mercaptopurine, methotrexate and vincristine, doxorubicin, dexamethasone, and cyclophosphamide, thioguanine, and cytarabine in ALL patients in first remission who are ineligible for allogeneic bone marrow transplantation. V. Evaluate the prognostic significance of cell surface immunophenotype, Philadelphia chromosome, and polymerase chain reaction detected BCR/abl fusion in this patient population.

OUTLINE: Patients are stratified according to age (15 to 29 vs 30 to 49 vs 50 to 65), performance status (0-1 vs 2-3), participating center, and candidate for allogeneic bone marrow transplantation (yes vs no). Patients receive induction chemotherapy consisting of daunorubicin IV on days 1-3, vincristine IV on days 1, 8, 15, and 22, oral prednisone on days 1-28, and asparaginase IV or intramuscularly (IM) on days 15-24. Patients with persistent leukemia on day 21, receive additional induction therapy consisting of daunorubicin IV on days 22 and 23, vincristine IV on days 29 and 36, and oral prednisone continuing to day 42. Patients with CNS leukemia receive additional therapy beginning on day 1 of induction chemotherapy consisting of methotrexate intrathecally (IT) or intraventricularly twice weekly until blasts are absent in spinal fluid. Patients receive oral leucovorin calcium every 6 hours for a total of 4 doses following each IT dose in the absence of blood count recovery. Following absence of spinal fluid blasts, patients receive methotrexate IT or intraventricularly weekly for 4 weeks then monthly for 1 year. Patients also receive cranial radiotherapy during consolidation therapy 5 days a week for 2.5 weeks. Patients with A1 bone marrow receive consolidation therapy following completion of induction therapy and blood count recovery. Patients receive consolidation therapy consisting of cyclophosphamide IV on days 1, 15, and 29, cytarabine IV on days 2-5, 9-12, 16-19, and 23-26, oral mercaptopurine on days 1-28, and methotrexate IT on days 2, 9, 16, and 23. Following completion of consolidation therapy, patients eligible for allogeneic bone marrow transplantation receive total body radiotherapy 3 times a day on days -7, -6, -5, and twice on day -4, and eptoposide IV over 4 hours on day -3. Patients undergo allogeneic bone marrow transplantation on day 0. Following completion of consolidation therapy, patients ineligible for allogeneic bone marrow transplantation receive maintenance therapy consisting of oral mercaptopurine on days 1-63, and oral methotrexate on days 1, 8, 15, 22, 29, 36, 43, 50, and 57. Patients receive subsequent courses of maintenance therapy when blood counts recover. Patients receive a second course of maintenance therapy consisting of vincristine IV on days 1, 8, 15, and 22, doxorubicin IV on days 1, 8, 15, and 22, and oral dexamethasone on days 1-28. Patients receive a third course consisting of cyclophosphamide IV on day 1, oral thioguanine on days 1-14, and cytarabine IV on days 3-6 and 10-13. Patients receive a fourth course consisting of oral mercaptopurine and oral methotrexate daily for 2 years. Patients are followed monthly for 6 months and then every 2 months thereafter.

PROJECTED ACCRUAL: A total of 25-50 patients will be accrued for this study.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

50 participants

Allocation:

Non-Randomized

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

TREATMENT OF ADULT ACUTE LYMPHOBLASTIC LEUKEMIA: PHASE II TRIALS OF AN INDUCTION REGIMEN INCLUDING PEG-L-ASPARAGINASE, WITH OR WITHOUT PIXY, IN PREVIOUSLY UNTREATED PATIENTS, FOLLOWED BY ALLOGENEIC BONE MARROW TRANSPLANTATION OR FURTHER CHEMOTHERAPY IN FIRST COMPLETE REMISSION

Study Start Date :

Jul 1, 1995

Actual Primary Completion Date :

Dec 1, 2001

Actual Study Completion Date :

Dec 1, 2003

Outcome Measures

Primary Outcome Measures

response []

Eligibility Criteria

Criteria

Ages Eligible for Study:

15 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

DISEASE CHARACTERISTICS: Histologically confirmed acute lymphocytic leukemia FAB class L1-L2 Mixed immunophenotypic markers with no cytochemical myeloid markers allowed No non-Hodgkin's lymphoma No chronic myelogenous leukemia in blast crisis Concurrent registration on the cytogenetics protocol SWOG-9007 required

PATIENT CHARACTERISTICS: Age: 15 to 65 Performance status: SWOG 0-3 Hematopoietic: Not specified Hepatic: Bilirubin no greater than 2 times normal (unless elevation due to leukemia) AST no greater than 3 times normal (unless elevation due to leukemia) No chronic liver disease Renal: Creatinine no greater than 2 times normal Cardiovascular: Left ventricular ejection fraction at least 50% by MUGA or echocardiogram No symptomatic congestive heart failure No symptomatic coronary artery disease No cardiomyopathy No uncontrolled arrhythmia Other: Not pregnant or nursing Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY: No prior remission induction chemotherapy for acute lymphocytic leukemia

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	MBCCOP - University of South Alabama	Mobile	Alabama	United States	36688
2	CCOP - Greater Phoenix	Phoenix	Arizona	United States	85006-2726
3	Veterans Affairs Medical Center - Phoenix (Hayden)	Phoenix	Arizona	United States	85012
4	Veterans Affairs Medical Center - Tucson	Tucson	Arizona	United States	85723
5	Arizona Cancer Center	Tucson	Arizona	United States	85724
6	University of Arkansas for Medical Sciences	Little Rock	Arkansas	United States	72205
7	Veterans Affairs Medical Center - Little Rock (McClellan)	Little Rock	Arkansas	United States	72205
8	Beckman Research Institute, City of Hope	Duarte	California	United States	91010
9	Veterans Affairs Medical Center - Long Beach	Long Beach	California	United States	90822
10	USC/Norris Comprehensive Cancer Center	Los Angeles	California	United States	90033-0800
11	Jonsson Comprehensive Cancer Center, UCLA	Los Angeles	California	United States	90095-1781
12	Veterans Affairs Outpatient Clinic - Martinez	Martinez	California	United States	94553
13	CCOP - Bay Area Tumor Institute	Oakland	California	United States	94609-3305
14	University of California Davis Medical Center	Sacramento	California	United States	95817
15	CCOP - Santa Rosa Memorial Hospital	Santa Rosa	California	United States	95403
16	David Grant Medical Center	Travis Air Force Base	California	United States	94535
17	Veterans Affairs Medical Center - Denver	Denver	Colorado	United States	80220
18	University of Colorado Cancer Center	Denver	Colorado	United States	80262
19	CCOP - Atlanta Regional	Atlanta	Georgia	United States	30342-1701
20	Dwight David Eisenhower Army Medical Center	Fort Gordon	Georgia	United States	30905-5650
21	Cancer Research Center of Hawaii	Honolulu	Hawaii	United States	96813
22	Veterans Affairs Medical Center - Hines (Hines Junior VA Hospital)	Hines	Illinois	United States	60141
23	Loyola University Medical Center	Maywood	Illinois	United States	60153
24	CCOP - Central Illinois	Springfield	Illinois	United States	62526
25	University of Kansas Medical Center	Kansas City	Kansas	United States	66160-7357
26	CCOP - Wichita	Wichita	Kansas	United States	67214-3882
27	Veterans Affairs Medical Center - Wichita	Wichita	Kansas	United States	67218
28	Veterans Affairs Medical Center - Lexington	Lexington	Kentucky	United States	40511-1093
29	Albert B. Chandler Medical Center, University of Kentucky	Lexington	Kentucky	United States	40536-0084
30	MBCCOP - LSU Medical Center	New Orleans	Louisiana	United States	70112
31	Tulane University School of Medicine	New Orleans	Louisiana	United States	70112
32	Veterans Affairs Medical Center - New Orleans	New Orleans	Louisiana	United States	70112
33	Louisiana State University Hospital - Shreveport	Shreveport	Louisiana	United States	71130-3932
34	Veterans Affairs Medical Center - Shreveport	Shreveport	Louisiana	United States	71130
35	Boston Medical Center	Boston	Massachusetts	United States	02118
36	Veterans Affairs Medical Center - Boston (Jamaica Plain)	Jamaica Plain	Massachusetts	United States	02130
37	Veterans Affairs Medical Center - Ann Arbor	Ann Arbor	Michigan	United States	48105
38	University of Michigan Comprehensive Cancer Center	Ann Arbor	Michigan	United States	48109-0752
39	Veterans Affairs Medical Center - Detroit	Detroit	Michigan	United States	48201-1932
40	Barbara Ann Karmanos Cancer Institute	Detroit	Michigan	United States	48201
41	Henry Ford Hospital	Detroit	Michigan	United States	48202
42	CCOP - Grand Rapids Clinical Oncology Program	Grand Rapids	Michigan	United States	49503
43	Providence Hospital - Southfield	Southfield	Michigan	United States	48075-9975
44	Veterans Affairs Medical Center - Biloxi	Biloxi	Mississippi	United States	39531-2410
45	University of Mississippi Medical Center	Jackson	Mississippi	United States	39216-4505
46	Veterans Affairs Medical Center - Jackson	Jackson	Mississippi	United States	39216
47	Keesler Medical Center - Keesler AFB	Keesler AFB	Mississippi	United States	39534-2576
48	Veterans Affairs Medical Center - Kansas City	Kansas City	Missouri	United States	64128
49	CCOP - Kansas City	Kansas City	Missouri	United States	64131
50	St. Louis University Health Sciences Center	Saint Louis	Missouri	United States	63110-0250
51	CCOP - St. Louis-Cape Girardeau	Saint Louis	Missouri	United States	63141
52	CCOP - Cancer Research for the Ozarks	Springfield	Missouri	United States	65807
53	CCOP - Montana Cancer Consortium	Billings	Montana	United States	59101
54	Veterans Affairs Medical Center - Albuquerque	Albuquerque	New Mexico	United States	87108-5138
55	University of New Mexico Cancer Research & Treatment Center	Albuquerque	New Mexico	United States	87131
56	Veterans Affairs Medical Center - Brooklyn	Brooklyn	New York	United States	11209
57	Herbert Irving Comprehensive Cancer Center	New York	New York	United States	10032
58	Barrett Cancer Center, The University Hospital	Cincinnati	Ohio	United States	45219
59	Veterans Affairs Medical Center - Cincinnati	Cincinnati	Ohio	United States	45220-2288
60	Cleveland Clinic Cancer Center	Cleveland	Ohio	United States	44195
61	CCOP - Columbus	Columbus	Ohio	United States	43206
62	Veterans Affairs Medical Center - Dayton	Dayton	Ohio	United States	45428
63	CCOP - Dayton	Kettering	Ohio	United States	45429
64	Oklahoma Medical Research Foundation	Oklahoma City	Oklahoma	United States	73104
65	Veterans Affairs Medical Center - Oklahoma City	Oklahoma City	Oklahoma	United States	73104
66	Oregon Cancer Center at Oregon Health Sciences University	Portland	Oregon	United States	97201-3098
67	Veterans Affairs Medical Center - Portland	Portland	Oregon	United States	97207
68	CCOP - Columbia River Program	Portland	Oregon	United States	97213
69	CCOP - Greenville	Greenville	South Carolina	United States	29615
70	CCOP - Upstate Carolina	Spartanburg	South Carolina	United States	29303
71	Brooke Army Medical Center	Fort Sam Houston	Texas	United States	78234
72	University of Texas Medical Branch	Galveston	Texas	United States	77555-1329
73	Texas Tech University Health Science Center	Lubbock	Texas	United States	79423
74	University of Texas Health Science Center at San Antonio	San Antonio	Texas	United States	78284
75	Veterans Affairs Medical Center - San Antonio (Murphy)	San Antonio	Texas	United States	78284
76	Veterans Affairs Medical Center - Temple	Temple	Texas	United States	76504
77	CCOP - Scott and White Hospital	Temple	Texas	United States	76508
78	Huntsman Cancer Institute	Salt Lake City	Utah	United States	84132
79	Veterans Affairs Medical Center - Salt Lake City	Salt Lake City	Utah	United States	84148
80	CCOP - Virginia Mason Research Center	Seattle	Washington	United States	98101
81	Swedish Cancer Institute	Seattle	Washington	United States	98104
82	Veterans Affairs Medical Center - Seattle	Seattle	Washington	United States	98108
83	CCOP - Northwest	Tacoma	Washington	United States	98405-0986