Induction Intensification in Treating Infants With Newly Diagnosed Acute Lymphoblastic Leukemia

Sponsor

Children's Oncology Group (Other)

Overall Status

Completed

CT.gov ID

NCT00002756

Collaborator

National Cancer Institute (NCI) (NIH)

221

Enrollment

140

Locations

Arm

189

Duration (Months)

1.6

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

RATIONALE: Drugs used in chemotherapy work in different ways to stop cancer cells from dividing so they stop growing or die. Combining more than one chemotherapy drug and giving them as induction intensification may kill more cancer cells.

PURPOSE: This phase II trial is studying how well induction intensification works in treating infants with newly diagnosed acute lymphocytic leukemia.

Condition or Disease	Intervention/Treatment	Phase
Leukemia	Biological: filgrastim Drug: asparaginase Drug: cyclophosphamide Drug: cytarabine Drug: daunorubicin hydrochloride Drug: etoposide Drug: leucovorin calcium Drug: mercaptopurine Drug: methotrexate Drug: prednisone Drug: therapeutic hydrocortisone Drug: vincristine sulfate	Phase 2

Detailed Description

OBJECTIVES:

Primary

Assess the feasibility of intensification with two courses of high-dose methotrexate followed by one course of cyclophosphamide/etoposide during induction and later as consolidation in infants with newly diagnosed acute lymphoblastic leukemia.
Determine event-free survival after shortened, intensive therapy in these patients.
Compare event-free survival rates of infants receiving this regimen whose leukemic blasts have or do not have translocations involving the 11q23 gene MLL.

Secondary

Correlate the presence of minimal residual disease at completion of induction, beginning of continuation, and at completion of therapy with patient outcome.
Investigate the clinical prognostic features that may be associated with outcome in infants, such as bone marrow blast content at day 8, white blood cell count, and age.
Correlate biologic characteristics of the leukemia cells at diagnosis (protocol POG-9900) with outcome in patients treated with this regimen.
Characterize patterns of gene expression associated with host and disease characteristics and treatment response in patients treated with this regimen.

OUTLINE: This is a multicenter study. Patients are stratified according to participating center and presence of CNS disease (yes vs no).

Patients receive induction chemotherapy comprising vincristine IV on days 1, 8, and 15; oral prednisone three times a day on days 1-21; daunorubicin IV over 30 minutes on days 1-2; cyclophosphamide IV over 30 minutes every 12 hours on days 3-4; and asparaginase intramuscularly (IM) on days 4, 6, 8, 10, 12, 15, 17, and 19. Patients also receive triple intrathecal therapy comprising methotrexate, hydrocortisone, and cytarabine on days 1, 8, and 15 and filgrastim (G-CSF) subcutaneously (SC) or IV beginning on day 5 and continuing until day 20, regardless of blood counts.

Patients receive induction intensification chemotherapy comprising high-dose methotrexate IV over 24 hours; triple intrathecal therapy as per induction therapy on days 22 and 29; and leucovorin calcium IV every 6 hours for 2 doses beginning 42 hours after start of high-dose methotrexate and then orally every 6 hours for 3 doses. Patients also receive etoposide IV over 2 hours and cyclophosphamide IV over 30 minutes on days 36-40. Patients receive G-CSF SC or IV beginning on day 41 and continuing until blood counts recover.

Patients achieving morphologic remission and recovery of blood counts while off G-CSF for 48 hours receive reinduction chemotherapy comprising the same regimen as in induction therapy with the exception of asparaginase IM beginning on day 1 (week 8) and continuing every Monday, Wednesday, and Friday for a total of 8 doses and triple intrathecal therapy on days 1 and 15 only (weeks 8 and 10). Patients receive G-CSF SC or IV beginning on day 5 and continuing until blood counts recover.

After blood count recovery, patients receive consolidation chemotherapy comprising triple intrathecal therapy as per induction therapy on day 1 (week 11); high-dose methotrexate IV over 24 hours on weeks 8 and 12; and leucovorin calcium IV every 6 hours for 2 doses beginning 42 hours after start of high-dose methotrexate and then orally every 6 hours for 3 doses. Patients also receive etoposide IV over 2 hours followed by cyclophosphamide IV over 30 minutes on days 15-19 (week 13). Patients receive G-CSF SC or IV beginning on day 20 and continuing until blood counts recover. On days 29-31 (week 15), patients receive high-dose cytarabine IV over 3 hours every 12 hours for 4 doses and asparaginase IM 6 hours after completion of high-dose cytarabine. Patients receive G-CSF beginning 24 hours after completion of asparaginase and continuing until blood counts recover.

Patients achieving morphologic remission and blood count recovery while off G-CSF for 48 hours receive continuation therapy comprising vincristine IV on day 1; oral prednisone three times a day on days 1-5; and triple intrathecal therapy on day 1 (weeks 18 and 22). Patients also receive methotrexate IM once a week and oral mercaptopurine daily on weeks 19-21, 23, and 24. On week 25, patients receive etoposide IV over 2 hours daily followed by cyclophosphamide IV over 30 minutes daily on days 1-5 and G-CSF SC or IV beginning on day 6 and continuing until blood counts recover. Patients receive an additional course of continuation therapy on weeks 28-35. On weeks 38-48, patients receive another identical course of continuation therapy with the exclusion of the etoposide and cyclophosphamide combination regimen.

Patients are followed monthly for 1 year, every 2 months for 1 year, every 3 months for 1 year, every 6 months for 1 year, and then annually thereafter.

PROJECTED ACCRUAL: Approximately 58-104 patients will be accrued for this study within 2.1 years.

Study Design

Study Type:

Interventional

Actual Enrollment :

221 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Induction Intensification in Infant ALL: A Children's Oncology Group Study

Study Start Date :

Jun 1, 1996

Actual Primary Completion Date :

Sep 1, 2007

Actual Study Completion Date :

Mar 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Chemo (Reduced Induction) No BMT (Open February 2004)	Biological: filgrastim Drug: asparaginase Drug: cyclophosphamide Drug: cytarabine Drug: daunorubicin hydrochloride Drug: etoposide Drug: leucovorin calcium Drug: mercaptopurine Drug: methotrexate Drug: prednisone Drug: therapeutic hydrocortisone Drug: vincristine sulfate

Arm

Intervention/Treatment

Experimental: Chemo (Reduced Induction) No BMT (Open February 2004)

Biological: filgrastim

Drug: asparaginase

Drug: cyclophosphamide

Drug: cytarabine

Drug: daunorubicin hydrochloride

Drug: etoposide

Drug: leucovorin calcium

Drug: mercaptopurine

Drug: methotrexate

Drug: prednisone

Drug: therapeutic hydrocortisone

Drug: vincristine sulfate

Outcome Measures

Primary Outcome Measures

Feasibility of intensification []
Event-free survival []
Comparison of event-free survival rates in infants with and without leukemic blasts translocations []

Secondary Outcome Measures

Correlation of minimal residual disease at completion of induction, beginning of continuation, and at completion of therapy with patient outcome []
Clinical prognostic features associated with outcome []
Correlation of biologic characteristics of leukemia cells at diagnosis with outcome []
Patterns of gene expression []

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A to 1 Year

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

DISEASE CHARACTERISTICS:

Newly diagnosed acute lymphoblastic leukemia (ALL) or acute undifferentiated leukemia
No infants less than 36 weeks' gestation
CNS or testicular disease permitted
No B-cell ALL or acute myeloid leukemia
Previously untreated except for the following:
Steroid treatment within 48 hours of diagnosis allowed with physical examination and differential CBC immediately prior to beginning steroids
Concurrent registration on protocol POG-9900 (ALL classification study) required
Patients registered on POG-9407 are eligible for the pharmacokinetic part of the study

PATIENT CHARACTERISTICS:

Age:

Under 1 at diagnosis

Performance status:

Not specified

Life expectancy:

Not specified

Hematopoietic:

Not specified

Hepatic:

Not specified

Renal:

Not specified

Other:

No uncontrolled infection
Adequate major organ function

PRIOR CONCURRENT THERAPY:

Biologic therapy:

Not specified

Chemotherapy:

Not specified

Endocrine therapy:

See Disease Characteristics
No concurrent chronic steroid treatment

Radiotherapy:

Not specified

Surgery:

Not specified

Other:

No other concurrent anticancer therapy

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Comprehensive Cancer Center at University of Alabama at Birmingham	Birmingham	Alabama	United States	35294
2	Phoenix Children's Hospital	Phoenix	Arizona	United States	85016-7710
3	Arkansas Cancer Research Center at University of Arkansas for Medical Sciences	Little Rock	Arkansas	United States	72205
4	Southern California Permanente Medical Group	Downey	California	United States	90242-2814
5	Loma Linda University Cancer Institute at Loma Linda University Medical Center	Loma Linda	California	United States	92354
6	Jonathan Jaques Children's Cancer Center at Miller Children's Hospital	Long Beach	California	United States	90801
7	Children's Hospital Central California	Madera	California	United States	93638-8762
8	Children's Hospital and Research Center - Oakland	Oakland	California	United States	94609-1809
9	Children's Hospital of Orange County	Orange	California	United States	92868
10	Sutter Cancer Center	Sacramento	California	United States	95816
11	Kaiser Permanente Medical Center - Oakland	Sacramento	California	United States	95825
12	Children's Hospital and Health Center - San Diego	San Diego	California	United States	92123-4282
13	UCSF Comprehensive Cancer Center	San Francisco	California	United States	94115
14	Santa Barbara Cottage Children's Hospital	Santa Barbara	California	United States	93105
15	Stanford Cancer Center at Stanford University Medical Center	Stanford	California	United States	94305
16	Carole and Ray Neag Comprehensive Cancer Center at the University of Connecticut Health Center	Farmington	Connecticut	United States	06360-2875
17	Yale Cancer Center	New Haven	Connecticut	United States	06520-8028
18	Children's National Medical Center	Washington	District of Columbia	United States	20010-2970
19	Lee Cancer Care of Lee Memorial Health System	Fort Myers	Florida	United States	33901
20	Broward General Medical Center Cancer Center	Ft. Lauderdale	Florida	United States	33316
21	University of Florida Shands Cancer Center	Gainesville	Florida	United States	32610-0232
22	Nemours Children's Clinic	Jacksonville	Florida	United States	32207
23	Baptist-South Miami Regional Cancer Program	Miami	Florida	United States	33176
24	Florida Hospital Cancer Institute at Florida Hospital Orlando	Orlando	Florida	United States	32803-1273
25	Nemours Children's Clinic - Orlando	Orlando	Florida	United States	32806
26	Sacred Heart Cancer Center at Sacred Heart Hospital	Pensacola	Florida	United States	32504
27	St. Joseph's Cancer Institute at St. Joseph's Hospital	Tampa	Florida	United States	33607
28	Kaplan Cancer Center at St. Mary's Medical Center	West Palm Beach	Florida	United States	33407
29	Winship Cancer Institute of Emory University	Atlanta	Georgia	United States	30322
30	Curtis & Elizabeth Anderson Cancer Institute at Memorial Health University Medical Center	Savannah	Georgia	United States	31403-3089
31	Cancer Research Center of Hawaii	Honolulu	Hawaii	United States	95813
32	St. Luke's Mountain States Tumor Institute - Boise	Boise	Idaho	United States	83712-6297
33	Children's Memorial Hospital - Chicago	Chicago	Illinois	United States	60614
34	Advocate Christ Medical Center	Oak Lawn	Illinois	United States	60453
35	Lutheran General Cancer Care Center	Park Ridge	Illinois	United States	60068-1174
36	Southern Illinois University School of Medicine	Springfield	Illinois	United States	62794-9620
37	St. Vincent Indianapolis Hospital	Indianapolis	Indiana	United States	46260
38	Blank Children's Hospital	Des Moines	Iowa	United States	50309
39	Holden Comprehensive Cancer Center at University of Iowa	Iowa City	Iowa	United States	52242-1083
40	Kansas Masonic Cancer Research Institute at the University of Kansas Medical Center	Kansas City	Kansas	United States	66160-7357
41	Via Christi Cancer Center at Via Christi Regional Medical Center	Wichita	Kansas	United States	67214
42	Markey Cancer Center at University of Kentucky Chandler Medical Center	Lexington	Kentucky	United States	40536-0293
43	Kosair Children's Hospital	Louisville	Kentucky	United States	40232
44	Children's Hospital of New Orleans	New Orleans	Louisiana	United States	70118
45	Ochsner Cancer Institute at Ochsner Clinic Foundation	New Orleans	Louisiana	United States	70121
46	CancerCare of Maine at Eastern Maine Medial Center	Bangor	Maine	United States	04401
47	Alvin and Lois Lapidus Cancer Institute at Sinai Hospital	Baltimore	Maryland	United States	21215
48	Floating Hospital for Children at Tufts - New England Medical Center	Boston	Massachusetts	United States	02111
49	C.S. Mott Children's Hospital at University of Michigan	Ann Arbor	Michigan	United States	48109-0238
50	Barbara Ann Karmanos Cancer Institute	Detroit	Michigan	United States	48201-1379
51	Hurley Medical Center	Flint	Michigan	United States	48503
52	Spectrum Health Cancer Care - Butterworth Campus	Grand Rapids	Michigan	United States	49503-2560
53	Van Elslander Cancer Center at St. John Hospital and Medical Center	Grosse Pointe Woods	Michigan	United States	48236
54	CCOP - Kalamazoo	Kalamazoo	Michigan	United States	49007-5341
55	Breslin Cancer Center at Ingham Regional Medical Center	Lansing	Michigan	United States	48910
56	Children's Hospitals and Clinics of Minneapolis	Minneapolis	Minnesota	United States	55404
57	University of Minnesota Medical Center - Fairview	Minneapolis	Minnesota	United States	55455
58	Mayo Clinic Cancer Center	Rochester	Minnesota	United States	55905
59	University of Mississippi Medical Center	Jackson	Mississippi	United States	39216-4505
60	Keesler Medical Center - Keesler Air Force Base	Keesler AFB	Mississippi	United States	39534-2511
61	Ellis Fischel Cancer Center at University of Missouri - Columbia	Columbia	Missouri	United States	65203
62	Children's Mercy Hospital	Kansas City	Missouri	United States	64108
63	Cardinal Glennon Children's Hospital	St. Louis	Missouri	United States	63104
64	Siteman Cancer Center at Barnes-Jewish Hospital	St. Louis	Missouri	United States	63110
65	Sunrise Hospital and Medical Center	Las Vegas	Nevada	United States	89109-2306
66	Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center	Lebanon	New Hampshire	United States	03756-0002
67	Hackensack University Medical Center Cancer Center	Hackensack	New Jersey	United States	07601
68	Newark Beth Israel Medical Center	Newark	New Jersey	United States	07112
69	St. Joseph's Hospital and Medical Center	Paterson	New Jersey	United States	07503
70	University of New Mexico Cancer Research and Treatment Center	Albuquerque	New Mexico	United States	87131-5636
71	Albert Einstein Cancer Center at Albert Einstein College of Medicine	Bronx	New York	United States	10461
72	Maimonides Medical Center	Brooklyn	New York	United States	11219
73	Roswell Park Cancer Institute	Buffalo	New York	United States	14263-0001
74	Winthrop University Hospital	Mineola	New York	United States	11501
75	Schneider Children's Hospital	New Hyde Park	New York	United States	11040
76	NYU Cancer Institute at New York University Medical Center	New York	New York	United States	10016
77	Mount Sinai Medical Center	New York	New York	United States	10029
78	Stony Brook University Cancer Center	Stony Brook	New York	United States	11794-8174
79	SUNY Upstate Medical University Hospital	Syracuse	New York	United States	13210
80	New York Medical College	Valhalla	New York	United States	10595
81	Mission Hospitals - Memorial Campus	Asheville	North Carolina	United States	28801
82	Blumenthal Cancer Center at Carolinas Medical Center	Charlotte	North Carolina	United States	28232-2861
83	Presbyterian Cancer Center at Presbyterian Hospital	Charlotte	North Carolina	United States	28233-3549
84	Wake Forest University Comprehensive Cancer Center	Winston-Salem	North Carolina	United States	27157-1096
85	Children's Hospital Medical Center of Akron	Akron	Ohio	United States	44308-1062
86	Cincinnati Children's Hospital Medical Center	Cincinnati	Ohio	United States	45229-3039
87	Rainbow Babies and Children's Hospital	Cleveland	Ohio	United States	44106-5000
88	Cleveland Clinic Taussig Cancer Center	Cleveland	Ohio	United States	44195-5217
89	Toledo Hospital	Toledo	Ohio	United States	43606
90	Medical University of Ohio Cancer Center	Toledo	Ohio	United States	43614
91	Tod Children's Hospital - Forum Health	Youngstown	Ohio	United States	44501
92	Oklahoma University Medical Center	Oklahoma City	Oklahoma	United States	73104
93	Natalie Warren Bryant Cancer Center at St. Francis Hospital	Tulsa	Oklahoma	United States	74136
94	Legacy Emanuel Hospital and Health Center & Children's Hospital	Portland	Oregon	United States	97227
95	Geisinger Medical Center	Danville	Pennsylvania	United States	17822-0001
96	Penn State Cancer Institute at Milton S. Hershey Medical Center	Hershey	Pennsylvania	United States	17033-0850
97	Children's Hospital of Pittsburgh	Pittsburgh	Pennsylvania	United States	15213
98	Rhode Island Hospital Comprehensive Cancer Center	Providence	Rhode Island	United States	02903
99	Hollings Cancer Center at Medical University of South Carolina	Charleston	South Carolina	United States	29425
100	Greenville Hospital System Cancer Center	Greenville	South Carolina	United States	29605
101	Sioux Valley Hospital and University of South Dakota Medical Center	Sioux Falls	South Dakota	United States	57117-5039
102	East Tennessee Children's Hospital	Knoxville	Tennessee	United States	37916
103	Vanderbilt-Ingram Cancer Center	Nashville	Tennessee	United States	37232-6310
104	Texas Tech University Health Sciences Center School of Medicine - Amarillo	Amarillo	Texas	United States	79106
105	Medical City Dallas Hospital	Dallas	Texas	United States	75230
106	Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - Dallas	Dallas	Texas	United States	75390
107	Cook Children's Medical Center - Fort Worth	Fort Worth	Texas	United States	76104-9958
108	University of Texas Medical Branch	Galveston	Texas	United States	77555-0209
109	Baylor University Medical Center - Houston	Houston	Texas	United States	77030-2399
110	Covenant Children's Hospital	Lubbock	Texas	United States	79410
111	University of Texas Health Science Center at San Antonio	San Antonio	Texas	United States	78207
112	Methodist Children's Hospital of South Texas	San Antonio	Texas	United States	78229-3993
113	CCOP - Scott and White Hospital	Temple	Texas	United States	76508
114	Primary Children's Medical Center	Salt Lake City	Utah	United States	84113-1100
115	Fletcher Allen Health Care - University Health Center Campus	Burlington	Vermont	United States	05405
116	INOVA Fairfax Hospital	Fairfax	Virginia	United States	22031
117	Children's Hospital of the King's Daughters	Norfolk	Virginia	United States	23507-1971
118	Naval Medical Center - Portsmouth	Portsmouth	Virginia	United States	23708-2197
119	Massey Cancer Center at Virginia Commonwealth University	Richmond	Virginia	United States	23298-0037
120	Carilion Cancer Center of Western Virginia	Roanoke	Virginia	United States	24029
121	Providence Cancer Center at Sacred Heart Medical Center	Spokane	Washington	United States	99220-2555
122	West Virginia University - Robert C. Byrd Health Sciences Center - Charleston Division	Charleston	West Virginia	United States	25302
123	Edwards Comprehensive Cancer Center at Cabell Huntington Hospital	Huntington	West Virginia	United States	25701
124	Mary Babb Randolph Cancer Center at West Virginia University Hospitals	Morgantown	West Virginia	United States	26506
125	St. Vincent Hospital Regional Cancer Center	Green Bay	Wisconsin	United States	54307-3508
126	University of Wisconsin Comprehensive Cancer Center	Madison	Wisconsin	United States	53792-6164
127	Marshfield Clinic - Marshfield Center	Marshfield	Wisconsin	United States	54449
128	Midwest Children's Cancer Center	Milwaukee	Wisconsin	United States	53226
129	Princess Margaret Hospital for Children	Perth	Western Australia	Australia	6001
130	Alberta Children's Hospital	Calgary	Alberta	Canada	T2T 5C7
131	Children's & Women's Hospital of British Columbia	Vancouver	British Columbia	Canada	V6H 3V4
132	CancerCare Manitoba	Winnipeg	Manitoba	Canada	R3E 0V9
133	IWK Health Centre	Halifax	Nova Scotia	Canada	B3K 6R8
134	Hospital for Sick Children	Toronto	Ontario	Canada	M5G 1X8
135	Montreal Children's Hospital at McGill University Health Center	Montreal	Quebec	Canada	H3H 1P3
136	Allan Blair Cancer Centre at Pasqua Hospital	Regina	Saskatchewan	Canada	S4T 7T1
137	Saskatoon Cancer Centre at the University of Saskatchewan	Saskatoon	Saskatchewan	Canada	S7N 4H4
138	Swiss Pediatric Oncology Group Bern	Bern		Switzerland	3010
139	Swiss Pediatric Oncology Group Geneva	Geneva		Switzerland	1205
140	Swiss Pediatric Oncology Group Lausanne	Lausanne		Switzerland	1011