Combination Chemotherapy With or Without Donor Bone Marrow Transplantation in Treating Infants With Previously Untreated Acute Lymphoblastic Leukemia

Sponsor

Children's Oncology Group (Other)

Overall Status

Completed

CT.gov ID

NCT00022126

Collaborator

National Cancer Institute (NCI) (NIH)

Enrollment

Locations

Arm

Duration (Months)

0.1

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. Giving the drugs in different combinations may kill more cancer cells. Bone marrow transplantation allows the doctor to give higher doses of chemotherapy and kill more cancer cells.

PURPOSE: Phase II trial to compare the effectiveness of combination chemotherapy with or without donor bone marrow transplantation in treating infants who have previously untreated acute lymphoblastic leukemia.

Condition or Disease	Intervention/Treatment	Phase
Leukemia	Drug: asparaginase Drug: cyclophosphamide Drug: cyclosporine Drug: cytarabine Drug: daunorubicin hydrochloride Drug: dexamethasone Drug: doxorubicin hydrochloride Drug: mercaptopurine Drug: methotrexate Drug: methylprednisolone Drug: pegaspargase Drug: thioguanine Drug: vincristine sulfate Procedure: allogeneic bone marrow transplantation Radiation: radiation therapy	Phase 2

Detailed Description

OBJECTIVES:

Determine the feasibility of dexamethasone-based induction chemotherapy followed by augmented Berlin-Frankfurt-Munster (BFM) consolidation chemotherapy with or without allogeneic bone marrow transplantation in infants with previously untreated acute lymphoblastic leukemia.
Determine the event-free survival of patients treated with this regimen.
Determine the clinical prognostic features associated with outcome in these patients.
Compare the biologic characteristics of the leukemia cells with outcome in these patients.

OUTLINE: This is a multicenter study.

Patients receive induction therapy comprising oral dexamethasone 3 times daily on days 1-14; daunorubicin IV on days 1, 8, and 15; vincristine IV on days 1, 8, 15, and 22; and asparaginase intramuscularly (IM) on days 4, 6, 8, 11, 13, 15, 18, 20, and 22. Patients also receive methotrexate intrathecally (IT) on days 1, 8, and 15 (and days 4 and 22 for overt CNS disease).

Patients with M1 or M2 marrow after induction therapy receive augmented consolidation therapy when blood counts recover. Patients receive cyclophosphamide IV on days 1 and 29; cytarabine IV or subcutaneously (SC) on days 2-5, 9-12, 30-33, and 37-40; oral mercaptopurine on days 1-14 and 29-42; vincristine IV on days 15, 22, 43, and 50; pegaspargase IM on days 15 and 43; and methotrexate IT on days 1, 8, and 15.

Patients who do not receive bone marrow transplantation (BMT) proceed to interim maintenance #1 when blood counts recover. Patients receive methotrexate IT on days 1, 11, 22, and 32; methotrexate IV and vincristine IV on days 1, 11, 22, 32, and 43; and pegaspargase IM on days 2 and 23.

When blood counts recover, patients receive delayed intensification #1 comprising vincristine IV on days 1, 8, 15, 43, and 50; doxorubicin IV on days 1, 8, and 15; oral dexamethasone 3 times daily on days 1-7 and 15-21; pegaspargase IM on days 4 and 43; cyclophosphamide IV on day 29; methotrexate IT on days 29 and 36; oral thioguanine on days 29-42; and cytarabine IV or SC on days 30-33 and 37-40.

When blood counts recover, patients receive interim maintenance #2 comprising vincristine as in interim maintenance #1; methotrexate IT on day 1 and IV on days 1, 11, 22, 32, and 41; and pegaspargase IM on days 2 and 23.

When blood counts recover, patients receive delayed intensification #2 comprising vincristine, doxorubicin, dexamethasone, pegaspargase, cyclophosphamide, cytarabine, and thioguanine as in intensification #1. Patients also receive methotrexate IT on days 1 and 29.

When blood counts recover, patients receive maintenance therapy comprising methotrexate IT on day 1 and orally on days 1, 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78; vincristine IV on days 1, 29, and 57; oral dexamethasone 3 times daily on days 1-5, 29-33, and 57-61; and oral mercaptopurine daily. Treatment repeats every 84 days for 6 courses.

Patients with an allergy to pegaspargase replace it with asparaginase IM on the days after receiving methotrexate IV during interim maintenance #1 and #2 and daily over 6 days in place of each dose of pegaspargase during delayed intensification #1 and #2.

After augmented consolidation therapy, patients meeting the following criteria may receive

BMT in place of chemotherapy:

In remission
Exhibiting chromosome translocation involving 11q23 or Ph+{(9;22)}
Available HLA-A, B, DR genotypic identical relative donor
No uncontrolled infection
Adequate organ function Within 3-4 weeks of consolidation therapy, patients undergoing allogeneic BMT receive cytarabine IV over 1 hour on days -8 to -5; cyclophosphamide IV over 30 minutes on days -7 and -6; and methylprednisolone IV twice daily on days -2 to

Patients also undergo total body irradiation twice daily on days -3 to 0. Patients receive allogeneic BMT on day 0. Patients also receive cyclosporine IV every 12 hours beginning on day -1, switching to oral when possible, and continuing until day 60. Patients then taper cyclosporine over the next 60-120 days.

Patients are followed every 2 months for 1 year, every 3 months for 1 year, every 4 months for 1 year, every 6 months for 1-2 years, and then annually thereafter.

PROJECTED ACCRUAL: A maximum of 20-40 patients will be accrued for this study within 2 years.

Study Design

Study Type:

Interventional

Actual Enrollment :

6 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Study of Modified Augmented BFM Therapy for Infants With Acute Lymphoblastic Leukemia

Study Start Date :

Nov 1, 2002

Actual Primary Completion Date :

Jan 1, 2005

Actual Study Completion Date :

Apr 1, 2006

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Modified Augmented BFM Therapy	Drug: asparaginase Drug: cyclophosphamide Drug: cyclosporine Drug: cytarabine Drug: daunorubicin hydrochloride Drug: dexamethasone Drug: doxorubicin hydrochloride Drug: mercaptopurine Drug: methotrexate Drug: methylprednisolone Drug: pegaspargase Drug: thioguanine Drug: vincristine sulfate Procedure: allogeneic bone marrow transplantation Radiation: radiation therapy

Arm

Intervention/Treatment

Experimental: Modified Augmented BFM Therapy

Drug: asparaginase

Drug: cyclophosphamide

Drug: cyclosporine

Drug: cytarabine

Drug: daunorubicin hydrochloride

Drug: dexamethasone

Drug: doxorubicin hydrochloride

Drug: mercaptopurine

Drug: methotrexate

Drug: methylprednisolone

Drug: pegaspargase

Drug: thioguanine

Drug: vincristine sulfate

Procedure: allogeneic bone marrow transplantation

Radiation: radiation therapy

Outcome Measures

Primary Outcome Measures

Establish whether the CCG Augmented Regimen (AR) can be successfully administered in the infant age group []

Secondary Outcome Measures

Grade 3 or 4 non-hematologic toxicity rates []
Event-free survival []

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A to 1 Year

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

DISEASE CHARACTERISTICS:

Diagnosis of previously untreated acute lymphoblastic leukemia (ALL) or acute undifferentiated leukemia
CNS or testicular disease allowed
No L3 sIg+ ALL or acute myelogenous leukemia
At least 36 weeks gestation for congenital ALL

PATIENT CHARACTERISTICS:

Age:

Under 366 days at diagnosis

Performance status:

Not specified

Life expectancy:

Not specified

Hematopoietic:

Not specified

Hepatic:

Not specified

Renal:

Not specified

PRIOR CONCURRENT THERAPY:

Biologic therapy:

Not specified

Chemotherapy:

Not specified

Endocrine therapy:

Steroid therapy within 48 hours of study allowed if complete blood counts and lumbar puncture results known
No chronic steroid treatment for other disease

Radiotherapy:

Not specified

Surgery:

Not specified

Other:

No other concurrent cytotoxic therapy

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Phoenix Children's Hospital	Phoenix	Arizona	United States	85016
2	Loma Linda University Medical Center	Loma Linda	California	United States	92354
3	Children's Hospital Los Angeles	Los Angeles	California	United States	90027-0700
4	Jonsson Comprehensive Cancer Center, UCLA	Los Angeles	California	United States	90095-1781
5	Children's Hospital Central California	Madera	California	United States	93638-8762
6	Children's Hospital of Oakland	Oakland	California	United States	94609-1809
7	Chao Family Comprehensive Cancer Center at University of California Irvine Cancer Center	Orange	California	United States	92868
8	Children's Hospital of Orange County	Orange	California	United States	92868
9	Children's Hospital of Denver	Denver	Colorado	United States	80218-1088
10	University of Connecticut Health Center	Farmington	Connecticut	United States	06360-7106
11	Alfred I. duPont Hospital for Children	Wilmington	Delaware	United States	19899
12	Children's National Medical Center	Washington	District of Columbia	United States	20010-2970
13	Emory University Hospital - Atlanta	Atlanta	Georgia	United States	30322
14	Children's Healthcare of Atlanta - Scottish Rite	Atlanta	Georgia	United States	30342
15	University of Chicago Cancer Research Center	Chicago	Illinois	United States	60601
16	Indiana University Cancer Center	Indianapolis	Indiana	United States	46202-5289
17	John Stoddard Cancer Center at Iowa Methodist Medical Center	Des Moines	Iowa	United States	50309
18	Holden Comprehensive Cancer Center at University of Iowa	Iowa City	Iowa	United States	52242-1009
19	MBCCOP - LSU Health Sciences Center	New Orleans	Louisiana	United States	70112
20	University of Michigan Comprehensive Cancer Center	Ann Arbor	Michigan	United States	48109-0914
21	Children's Hospitals and Clinics - Minneapolis	Minneapolis	Minnesota	United States	55404
22	Children's Hospitals and Clinics - Minnesota	Saint Paul	Minnesota	United States	55102
23	Children's Mercy Hospital	Kansas City	Missouri	United States	64108
24	Cancer Institute of New Jersey	New Brunswick	New Jersey	United States	08903
25	Mount Sinai School of Medicine	New York	New York	United States	10029
26	Herbert Irving Comprehensive Cancer Center at Columbia University	New York	New York	United States	10032
27	Lineberger Comprehensive Cancer Center, UNC	Chapel Hill	North Carolina	United States	27599-7295
28	Children's Hospital Medical Center of Akron	Akron	Ohio	United States	44308
29	Cincinnati Children's Hospital Medical Center	Cincinnati	Ohio	United States	45229-3039
30	Children's Hospital of Columbus	Columbus	Ohio	United States	43205-2696
31	Children's Medical Center - Dayton	Dayton	Ohio	United States	45404
32	Doernbecher Children's Hospital	Portland	Oregon	United States	97201-3098
33	CCOP - Columbia River Oncology Program	Portland	Oregon	United States	97225
34	Penn State Cancer Institute at Milton S. Hershey Medical Center	Hershey	Pennsylvania	United States	17033-0850
35	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania	United States	19104
36	Children's Hospital of Pittsburgh	Pittsburgh	Pennsylvania	United States	15213
37	University of Texas - MD Anderson Cancer Center	Houston	Texas	United States	77030-4009
38	Baylor College of Medicine	Houston	Texas	United States	77030
39	Methodist Cancer Center	San Antonio	Texas	United States	78229-3902
40	CCOP - Scott and White Hospital	Temple	Texas	United States	76508
41	Huntsman Cancer Institute	Salt Lake City	Utah	United States	84112
42	Children's Hospital and Regional Medical Center - Seattle	Seattle	Washington	United States	98105
43	Deaconess Medical Center	Spokane	Washington	United States	99210-0248
44	Madigan Army Medical Center	Tacoma	Washington	United States	98431-5000
45	CCOP - St. Vincent Hospital Cancer Center, Green Bay	Green Bay	Wisconsin	United States	54301
46	University of Wisconsin Comprehensive Cancer Center	Madison	Wisconsin	United States	53792-6164
47	CCOP - Marshfield Clinic Research Foundation	Marshfield	Wisconsin	United States	54449
48	Women's and Children's Hospital	North Adelaide	South Australia	Australia	5006
49	Princess Margaret Hospital for Children	Perth	Western Australia	Australia	6006
50	British Columbia Children's Hospital	Vancouver	British Columbia	Canada	V6H 3V4
51	IWK Health Centre	Halifax	Nova Scotia	Canada	B3J 3G9