Induction Intensification in Treating Infants With Newly Diagnosed Acute Lymphoblastic Leukemia

Leukemia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00002756
• Other study ID #: P9407
• Secondary ID: COG-P9407POG-940
• Status: Completed
• Phase: Phase 2
• First received: November 1, 1999
• Last updated: February 12, 2014
• Start date: June 1996
• Est. completion date: March 2012

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 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 221
• Est. completion date: March 2012
• Est. primary completion date: September 2007
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A to 1 Year

Eligibility

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

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

Biological:
• filgrastim

Drug:
• asparaginase

• cyclophosphamide

• cytarabine

• daunorubicin hydrochloride

• etoposide

• leucovorin calcium

• mercaptopurine

• methotrexate

• prednisone

• therapeutic hydrocortisone

• vincristine sulfate

Locations

Country	Name	City	State
Australia	Princess Margaret Hospital for Children	Perth	Western Australia
Canada	Alberta Children's Hospital	Calgary	Alberta
Canada	IWK Health Centre	Halifax	Nova Scotia
Canada	Montreal Children's Hospital at McGill University Health Center	Montreal	Quebec
Canada	Allan Blair Cancer Centre at Pasqua Hospital	Regina	Saskatchewan
Canada	Saskatoon Cancer Centre at the University of Saskatchewan	Saskatoon	Saskatchewan
Canada	Hospital for Sick Children	Toronto	Ontario
Canada	Children's & Women's Hospital of British Columbia	Vancouver	British Columbia
Canada	CancerCare Manitoba	Winnipeg	Manitoba
Switzerland	Swiss Pediatric Oncology Group Bern	Bern
Switzerland	Swiss Pediatric Oncology Group Geneva	Geneva
Switzerland	Swiss Pediatric Oncology Group Lausanne	Lausanne
United States	Children's Hospital Medical Center of Akron	Akron	Ohio
United States	University of New Mexico Cancer Research and Treatment Center	Albuquerque	New Mexico
United States	Texas Tech University Health Sciences Center School of Medicine - Amarillo	Amarillo	Texas
United States	C.S. Mott Children's Hospital at University of Michigan	Ann Arbor	Michigan
United States	Mission Hospitals - Memorial Campus	Asheville	North Carolina
United States	Winship Cancer Institute of Emory University	Atlanta	Georgia
United States	Alvin and Lois Lapidus Cancer Institute at Sinai Hospital	Baltimore	Maryland
United States	CancerCare of Maine at Eastern Maine Medial Center	Bangor	Maine
United States	Comprehensive Cancer Center at University of Alabama at Birmingham	Birmingham	Alabama
United States	St. Luke's Mountain States Tumor Institute - Boise	Boise	Idaho
United States	Floating Hospital for Children at Tufts - New England Medical Center	Boston	Massachusetts
United States	Albert Einstein Cancer Center at Albert Einstein College of Medicine	Bronx	New York
United States	Maimonides Medical Center	Brooklyn	New York
United States	Roswell Park Cancer Institute	Buffalo	New York
United States	Fletcher Allen Health Care - University Health Center Campus	Burlington	Vermont
United States	Hollings Cancer Center at Medical University of South Carolina	Charleston	South Carolina
United States	West Virginia University - Robert C. Byrd Health Sciences Center - Charleston Division	Charleston	West Virginia
United States	Blumenthal Cancer Center at Carolinas Medical Center	Charlotte	North Carolina
United States	Presbyterian Cancer Center at Presbyterian Hospital	Charlotte	North Carolina
United States	Children's Memorial Hospital - Chicago	Chicago	Illinois
United States	Cincinnati Children's Hospital Medical Center	Cincinnati	Ohio
United States	Cleveland Clinic Taussig Cancer Center	Cleveland	Ohio
United States	Rainbow Babies and Children's Hospital	Cleveland	Ohio
United States	Ellis Fischel Cancer Center at University of Missouri - Columbia	Columbia	Missouri
United States	Medical City Dallas Hospital	Dallas	Texas
United States	Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - Dallas	Dallas	Texas
United States	Geisinger Medical Center	Danville	Pennsylvania
United States	Blank Children's Hospital	Des Moines	Iowa
United States	Barbara Ann Karmanos Cancer Institute	Detroit	Michigan
United States	Southern California Permanente Medical Group	Downey	California
United States	INOVA Fairfax Hospital	Fairfax	Virginia
United States	Carole and Ray Neag Comprehensive Cancer Center at the University of Connecticut Health Center	Farmington	Connecticut
United States	Hurley Medical Center	Flint	Michigan
United States	Lee Cancer Care of Lee Memorial Health System	Fort Myers	Florida
United States	Cook Children's Medical Center - Fort Worth	Fort Worth	Texas
United States	Broward General Medical Center Cancer Center	Ft. Lauderdale	Florida
United States	University of Florida Shands Cancer Center	Gainesville	Florida
United States	University of Texas Medical Branch	Galveston	Texas
United States	Spectrum Health Cancer Care - Butterworth Campus	Grand Rapids	Michigan
United States	St. Vincent Hospital Regional Cancer Center	Green Bay	Wisconsin
United States	Greenville Hospital System Cancer Center	Greenville	South Carolina
United States	Van Elslander Cancer Center at St. John Hospital and Medical Center	Grosse Pointe Woods	Michigan
United States	Hackensack University Medical Center Cancer Center	Hackensack	New Jersey
United States	Penn State Cancer Institute at Milton S. Hershey Medical Center	Hershey	Pennsylvania
United States	Cancer Research Center of Hawaii	Honolulu	Hawaii
United States	Baylor University Medical Center - Houston	Houston	Texas
United States	Edwards Comprehensive Cancer Center at Cabell Huntington Hospital	Huntington	West Virginia
United States	St. Vincent Indianapolis Hospital	Indianapolis	Indiana
United States	Holden Comprehensive Cancer Center at University of Iowa	Iowa City	Iowa
United States	University of Mississippi Medical Center	Jackson	Mississippi
United States	Nemours Children's Clinic	Jacksonville	Florida
United States	CCOP - Kalamazoo	Kalamazoo	Michigan
United States	Children's Mercy Hospital	Kansas City	Missouri
United States	Kansas Masonic Cancer Research Institute at the University of Kansas Medical Center	Kansas City	Kansas
United States	Keesler Medical Center - Keesler Air Force Base	Keesler AFB	Mississippi
United States	East Tennessee Children's Hospital	Knoxville	Tennessee
United States	Breslin Cancer Center at Ingham Regional Medical Center	Lansing	Michigan
United States	Sunrise Hospital and Medical Center	Las Vegas	Nevada
United States	Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center	Lebanon	New Hampshire
United States	Markey Cancer Center at University of Kentucky Chandler Medical Center	Lexington	Kentucky
United States	Arkansas Cancer Research Center at University of Arkansas for Medical Sciences	Little Rock	Arkansas
United States	Loma Linda University Cancer Institute at Loma Linda University Medical Center	Loma Linda	California
United States	Jonathan Jaques Children's Cancer Center at Miller Children's Hospital	Long Beach	California
United States	Kosair Children's Hospital	Louisville	Kentucky
United States	Covenant Children's Hospital	Lubbock	Texas
United States	Children's Hospital Central California	Madera	California
United States	University of Wisconsin Comprehensive Cancer Center	Madison	Wisconsin
United States	Marshfield Clinic - Marshfield Center	Marshfield	Wisconsin
United States	Baptist-South Miami Regional Cancer Program	Miami	Florida
United States	Midwest Children's Cancer Center	Milwaukee	Wisconsin
United States	Winthrop University Hospital	Mineola	New York
United States	Children's Hospitals and Clinics of Minneapolis	Minneapolis	Minnesota
United States	University of Minnesota Medical Center - Fairview	Minneapolis	Minnesota
United States	Mary Babb Randolph Cancer Center at West Virginia University Hospitals	Morgantown	West Virginia
United States	Vanderbilt-Ingram Cancer Center	Nashville	Tennessee
United States	Yale Cancer Center	New Haven	Connecticut
United States	Schneider Children's Hospital	New Hyde Park	New York
United States	Children's Hospital of New Orleans	New Orleans	Louisiana
United States	Ochsner Cancer Institute at Ochsner Clinic Foundation	New Orleans	Louisiana
United States	Mount Sinai Medical Center	New York	New York
United States	NYU Cancer Institute at New York University Medical Center	New York	New York
United States	Newark Beth Israel Medical Center	Newark	New Jersey
United States	Children's Hospital of the King's Daughters	Norfolk	Virginia
United States	Advocate Christ Medical Center	Oak Lawn	Illinois
United States	Children's Hospital and Research Center - Oakland	Oakland	California
United States	Oklahoma University Medical Center	Oklahoma City	Oklahoma
United States	Children's Hospital of Orange County	Orange	California
United States	Florida Hospital Cancer Institute at Florida Hospital Orlando	Orlando	Florida
United States	Nemours Children's Clinic - Orlando	Orlando	Florida
United States	Lutheran General Cancer Care Center	Park Ridge	Illinois
United States	St. Joseph's Hospital and Medical Center	Paterson	New Jersey
United States	Sacred Heart Cancer Center at Sacred Heart Hospital	Pensacola	Florida
United States	Phoenix Children's Hospital	Phoenix	Arizona
United States	Children's Hospital of Pittsburgh	Pittsburgh	Pennsylvania
United States	Legacy Emanuel Hospital and Health Center & Children's Hospital	Portland	Oregon
United States	Naval Medical Center - Portsmouth	Portsmouth	Virginia
United States	Rhode Island Hospital Comprehensive Cancer Center	Providence	Rhode Island
United States	Massey Cancer Center at Virginia Commonwealth University	Richmond	Virginia
United States	Carilion Cancer Center of Western Virginia	Roanoke	Virginia
United States	Mayo Clinic Cancer Center	Rochester	Minnesota
United States	Kaiser Permanente Medical Center - Oakland	Sacramento	California
United States	Sutter Cancer Center	Sacramento	California
United States	Primary Children's Medical Center	Salt Lake City	Utah
United States	Methodist Children's Hospital of South Texas	San Antonio	Texas
United States	University of Texas Health Science Center at San Antonio	San Antonio	Texas
United States	Children's Hospital and Health Center - San Diego	San Diego	California
United States	UCSF Comprehensive Cancer Center	San Francisco	California
United States	Santa Barbara Cottage Children's Hospital	Santa Barbara	California
United States	Curtis & Elizabeth Anderson Cancer Institute at Memorial Health University Medical Center	Savannah	Georgia
United States	Sioux Valley Hospital and University of South Dakota Medical Center	Sioux Falls	South Dakota
United States	Providence Cancer Center at Sacred Heart Medical Center	Spokane	Washington
United States	Southern Illinois University School of Medicine	Springfield	Illinois
United States	Cardinal Glennon Children's Hospital	St. Louis	Missouri
United States	Siteman Cancer Center at Barnes-Jewish Hospital	St. Louis	Missouri
United States	Stanford Cancer Center at Stanford University Medical Center	Stanford	California
United States	Stony Brook University Cancer Center	Stony Brook	New York
United States	SUNY Upstate Medical University Hospital	Syracuse	New York
United States	St. Joseph's Cancer Institute at St. Joseph's Hospital	Tampa	Florida
United States	CCOP - Scott and White Hospital	Temple	Texas
United States	Medical University of Ohio Cancer Center	Toledo	Ohio
United States	Toledo Hospital	Toledo	Ohio
United States	Natalie Warren Bryant Cancer Center at St. Francis Hospital	Tulsa	Oklahoma
United States	New York Medical College	Valhalla	New York
United States	Children's National Medical Center	Washington	District of Columbia
United States	Kaplan Cancer Center at St. Mary's Medical Center	West Palm Beach	Florida
United States	Via Christi Cancer Center at Via Christi Regional Medical Center	Wichita	Kansas
United States	Wake Forest University Comprehensive Cancer Center	Winston-Salem	North Carolina
United States	Tod Children's Hospital - Forum Health	Youngstown	Ohio

Sponsors (2)

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

Countries where clinical trial is conducted

United States,  Australia,  Canada,  Switzerland, 

References & Publications (6)

Dreyer ZE, Dinndorf PA, Camitta B, Sather H, La MK, Devidas M, Hilden JM, Heerema NA, Sanders JE, McGlennen R, Willman CL, Carroll AJ, Behm F, Smith FO, Woods WG, Godder K, Reaman GH. Analysis of the role of hematopoietic stem-cell transplantation in infants with acute lymphoblastic leukemia in first remission and MLL gene rearrangements: a report from the Children's Oncology Group. J Clin Oncol. 2011 Jan 10;29(2):214-22. doi: 10.1200/JCO.2009.26.8938. Epub 2010 Dec 6. — View Citation

Fernandez CV, Kodish E, Taweel S, Shurin S, Weijer C; Children's Oncology Group. Disclosure of the right of research participants to receive research results: an analysis of consent forms in the Children's Oncology Group. Cancer. 2003 Jun 1;97(11):2904-9. — View Citation

Kang H, Wilson CS, Harvey RC, Chen IM, Murphy MH, Atlas SR, Bedrick EJ, Devidas M, Carroll AJ, Robinson BW, Stam RW, Valsecchi MG, Pieters R, Heerema NA, Hilden JM, Felix CA, Reaman GH, Camitta B, Winick N, Carroll WL, Dreyer ZE, Hunger SP, Willman CL. Ge — View Citation

Robinson BW, Devidas M, Carroll AJ, et al.: Specific MLL partner genes in infant acute lymphoblastic leukemia (ALL) associated with outcome are linked to age and white blood cell count (WBC) at diagnosis: A report on the Children's Oncology Group (COG) P9

Salzer WL, Jones TL, Devidas M, Hilden JM, Winick N, Hunger S, Carroll WL, Camitta B, Dreyer ZE. Modifications to induction therapy decrease risk of early death in infants with acute lymphoblastic leukemia treated on Children's Oncology Group P9407. Pedia — View Citation

Thompson PA, Murry DJ, Rosner GL, Lunagomez S, Blaney SM, Berg SL, Camitta BM, Dreyer ZE, Bomgaars LR. Methotrexate pharmacokinetics in infants with acute lymphoblastic leukemia. Cancer Chemother Pharmacol. 2007 May;59(6):847-53. Epub 2006 Nov 29. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Feasibility of intensification			No
Primary	Event-free survival			No
Primary	Comparison of event-free survival rates in infants with and without leukemic blasts translocations			No
Secondary	Correlation of minimal residual disease at completion of induction, beginning of continuation, and at completion of therapy with patient outcome			No
Secondary	Clinical prognostic features associated with outcome			No
Secondary	Correlation of biologic characteristics of leukemia cells at diagnosis with outcome			No
Secondary	Patterns of gene expression			No