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

Leukemia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00022126
• Other study ID #: AALL01P1
• Secondary ID: COG-AALL01P1CDR0
• Status: Completed
• Phase: Phase 2
• First received: August 10, 2001
• Last updated: February 18, 2014
• Start date: November 2002
• Est. completion date: April 2006

Study information

• Verified date: February 2014
• Source: Children's Oncology Group
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial 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.

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

0. 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 6
• Est. completion date: April 2006
• Est. primary completion date: January 2005
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A to 1 Year

Eligibility

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

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Leukemia
• Leukemia, Lymphoid
• Precursor Cell Lymphoblastic Leukemia-Lymphoma

Intervention

Drug:
• asparaginase

• cyclophosphamide

• cyclosporine

• cytarabine

• daunorubicin hydrochloride

• dexamethasone

• doxorubicin hydrochloride

• mercaptopurine

• methotrexate

• methylprednisolone

• pegaspargase

• thioguanine

• vincristine sulfate

Procedure:
• allogeneic bone marrow transplantation

Radiation:
• radiation therapy

Locations

Country	Name	City	State
Australia	Women's and Children's Hospital	North Adelaide	South Australia
Australia	Princess Margaret Hospital for Children	Perth	Western Australia
Canada	IWK Health Centre	Halifax	Nova Scotia
Canada	British Columbia Children's Hospital	Vancouver	British Columbia
United States	Children's Hospital Medical Center of Akron	Akron	Ohio
United States	University of Michigan Comprehensive Cancer Center	Ann Arbor	Michigan
United States	Children's Healthcare of Atlanta - Scottish Rite	Atlanta	Georgia
United States	Emory University Hospital - Atlanta	Atlanta	Georgia
United States	Lineberger Comprehensive Cancer Center, UNC	Chapel Hill	North Carolina
United States	University of Chicago Cancer Research Center	Chicago	Illinois
United States	Cincinnati Children's Hospital Medical Center	Cincinnati	Ohio
United States	Children's Hospital of Columbus	Columbus	Ohio
United States	Children's Medical Center - Dayton	Dayton	Ohio
United States	Children's Hospital of Denver	Denver	Colorado
United States	John Stoddard Cancer Center at Iowa Methodist Medical Center	Des Moines	Iowa
United States	University of Connecticut Health Center	Farmington	Connecticut
United States	CCOP - St. Vincent Hospital Cancer Center, Green Bay	Green Bay	Wisconsin
United States	Penn State Cancer Institute at Milton S. Hershey Medical Center	Hershey	Pennsylvania
United States	Baylor College of Medicine	Houston	Texas
United States	University of Texas - MD Anderson Cancer Center	Houston	Texas
United States	Indiana University Cancer Center	Indianapolis	Indiana
United States	Holden Comprehensive Cancer Center at University of Iowa	Iowa City	Iowa
United States	Children's Mercy Hospital	Kansas City	Missouri
United States	Loma Linda University Medical Center	Loma Linda	California
United States	Children's Hospital Los Angeles	Los Angeles	California
United States	Jonsson Comprehensive Cancer Center, UCLA	Los Angeles	California
United States	Children's Hospital Central California	Madera	California
United States	University of Wisconsin Comprehensive Cancer Center	Madison	Wisconsin
United States	CCOP - Marshfield Clinic Research Foundation	Marshfield	Wisconsin
United States	Children's Hospitals and Clinics - Minneapolis	Minneapolis	Minnesota
United States	Cancer Institute of New Jersey	New Brunswick	New Jersey
United States	MBCCOP - LSU Health Sciences Center	New Orleans	Louisiana
United States	Herbert Irving Comprehensive Cancer Center at Columbia University	New York	New York
United States	Mount Sinai School of Medicine	New York	New York
United States	Children's Hospital of Oakland	Oakland	California
United States	Chao Family Comprehensive Cancer Center at University of California Irvine Cancer Center	Orange	California
United States	Children's Hospital of Orange County	Orange	California
United States	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania
United States	Phoenix Children's Hospital	Phoenix	Arizona
United States	Children's Hospital of Pittsburgh	Pittsburgh	Pennsylvania
United States	CCOP - Columbia River Oncology Program	Portland	Oregon
United States	Doernbecher Children's Hospital	Portland	Oregon
United States	Children's Hospitals and Clinics - Minnesota	Saint Paul	Minnesota
United States	Huntsman Cancer Institute	Salt Lake City	Utah
United States	Methodist Cancer Center	San Antonio	Texas
United States	Children's Hospital and Regional Medical Center - Seattle	Seattle	Washington
United States	Deaconess Medical Center	Spokane	Washington
United States	Madigan Army Medical Center	Tacoma	Washington
United States	CCOP - Scott and White Hospital	Temple	Texas
United States	Children's National Medical Center	Washington	District of Columbia
United States	Alfred I. duPont Hospital for Children	Wilmington	Delaware

Sponsors (2)

Lead Sponsor	Collaborator
Children's Oncology Group	National Cancer Institute (NCI)

Countries where clinical trial is conducted

United States,  Australia,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Establish whether the CCG Augmented Regimen (AR) can be successfully administered in the infant age group			Yes
Secondary	Grade 3 or 4 non-hematologic toxicity rates			Yes
Secondary	Event-free survival			No