Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Related Publications
Trial Contact Information
Related Information
Registry Information

Alternate Title

Combination Chemotherapy in Treating Young Patients With Newly Diagnosed Acute Lymphoblastic Leukemia

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase II Treatment Active 16 to 30 NCI CALGB-10403 CALGB 10403, CALGB-10403, ECOG C10403, SWOG C10403, NCT00558519

Objectives

1. To describe the outcomes (i.e., complete response rate, event-free survival, disease-free survival, and overall survival) of adolescents and young adults with newly diagnosed acute lymphoblastic leukemia (ALL) treated with a pediatric chemotherapy regimen by adult hematologists/oncologists at multiple sites.
2. To describe the toxicities observed in these patients.
3. To compare the outcomes of patients treated on this protocol with appropriate similar patients (by age and disease characteristics) treated by pediatric oncologists on protocol COG-AALL0232.
4. To evaluate the adherence of adult hematologists/oncologists and their patients to a "pediatric" ALL treatment regimen and identify reasons for variances.
5. To analyze and describe the outcomes of patients treated on this study according to pretreatment characteristics such as age, gender, white blood cell count, other hematologic parameters, blood chemistry, immunophenotype, cytogenetics and molecular genetic characteristics, and treatment variables such as treatment site (academic center or community), and protocol adherence.
6. To analyze and describe the outcomes of patients treated on this study according to baseline psychosocial characteristics, demographics, and family support.

Entry Criteria

Disease Characteristics:

• Newly diagnosed acute lymphoblastic leukemia (ALL)
  • B-precursor or T-precursor ALL
  • No Burkitt type leukemia (FAB L3; SIg positive; t(8;14) or variant)
  • No known Ph+ ALL at time of diagnosis



• Enrollment on CALGB-C10001 (or its successor trial) for CALGB patients with Philadelphia-positive ALL take priority over enrollment on this protocol
  • Patients enrolled on this study but are later found to meet the following criteria for Ph+ ALL eligibility criteria for protocol CALGB-C10001 (or its successor trial) are removed from this study and enrolled on CALGB-C10001 (or its successor study):
    • BCR-ABL fusion transcript determined by FISH or RT-PCR
    • t(9;22)(q34;q11) or variant determined by cytogenetics



• All CALGB patients are required to participate in CALGB-8461



• All SWOG patients are required to participate in SWOG-9007

Prior/Concurrent Therapy:

• No prior therapy for acute leukemia except emergency therapy (i.e., corticosteroids or hydroxyurea) for blast cell crisis, superior vena cava syndrome, or renal failure due to leukemic infiltration of the kidneys
• Single-dose intrathecal cytarabine is allowed prior to registration for patient convenience provided systemic chemotherapy begins within 72 hours of intrathecal therapy
• Prior steroid therapy allowed

Patient Characteristics:

• ECOG performance status 0-2
• No Down syndrome

Expected Enrollment

Outcomes

Complete response rate
Event-free survival
Disease-free survival
Overall survival
Toxicity
Outcomes of adolescent and young adult patients treated on this study compared with those of patients treated per COG-AALL0232
Adherence of adult hematologists/oncologists and their patients to a "pediatric" acute lymphoblastic leukemia treatment regimen and identification of reasons for variances
Outcomes of patients treated on this study according to pretreatment characteristics such as age, gender, white blood cell count, other hematologic parameters, blood chemistry, immunophenotype, cytogenetics and molecular genetic characteristics
Outcomes of patients treated on this study according to treatment variables such as treatment site (academic center or community), and protocol adherence
Analysis and description of the outcomes of patients treated on this study according to baseline psychosocial characteristics, demographics, and family support

Outline

This is a multicenter study.

• Remission induction therapy: Patients receive intrathecal (IT) cytarabine on day 1; vincristine IV on days 1, 8, 15, and 22; dexamethasone IV or orally twice daily on days 1-14; daunorubicin hydrochloride IV on days 1, 8, 15, and 22; pegaspargase IV or intramuscularly (IM) on day 4 or 5 or 6; and IT methotrexate on days 8 and 29*. Patients undergo bone marrow aspirate (BMA) and biopsy on day 29 to assess induction response and minimal residual disease status. Patients with M1 marrow (< 1% lymphoblasts) proceed to remission consolidation therapy. Patients with M2 marrow (> 5% but < 25% lymphoblasts) proceed to extended remission induction therapy. Patients with M3 marrow are removed from protocol therapy.

   [Note: *Patients with CNS3 disease also receive IT methotrexate on days 15 and 22.]




• Extended remission induction therapy: Patients receive dexamethasone IV or orally twice daily on days 1-14; vincristine IV on days 1 and 8; pegaspargase IM or IV on day 4 or 5 or 6; and daunorubicin hydrochloride IV on day 1. Patients undergo BMA and biopsy on day 15. Patients with M1 marrow proceed to remission consolidation therapy. Patients with M2 or M3 bone marrow are removed from protocol therapy.



• Remission consolidation therapy: Patients receive cyclophosphamide IV on days 1 and 29; cytarabine IV or subcutaneously (SC) on days 1-4, 8-11, 29-32, and 36-39; oral mercaptopurine on days 1-14 and 29-42; vincristine IV on days 15, 22, 43, and 50; pegaspargase IM or IV on days 15 and 43; and IT methotrexate on days 1, 8, 15*, and 22*. Once blood counts recover, patients proceed to interim maintenance therapy.

   [Note: *Patients with CNS3 disease do not receive IT methotrexate on days 15 and 22.]




• Interim maintenance therapy: Patients receive vincristine IV and methotrexate (Capizzi methotrexate) IV on days 1, 11, 21, 31, and 41, pegaspargase IM or IV on days 2 and 22, and IT methotrexate on days 1 and 31. Once blood counts recover (ANC ≥ 750/mm³ and platelet count ≥ 75,000/mm³), patients proceed to delayed intensification therapy.



• Delayed intensification therapy: Patients receive vincristine IV on days 1, 8, 15, 43, and 50; dexamethasone IV or orally twice daily on days 1-7 and 15-21; doxorubicin hydrochloride IV on days 1, 8, and 15; pegaspargase IM or IV on day 4 or 5 or 6 AND day 43; cyclophosphamide IV on day 29; cytarabine IV or SC on days 29-32 and 36-39; oral thioguanine on days 29-42; and IT methotrexate on days 1, 29, and 36. Once blood counts recover, patients proceed to maintenance therapy.



• Maintenance chemotherapy: Patients receive vincristine IV on days 1, 29, and 57; dexamethasone IV or orally twice daily on days 1-5, 29-33, and 57-61; mercaptopurine orally on days 1-84; IT methotrexate on day 1*; and oral methotrexate on days 8, 15, 22, 29**, 36, 43, 50, 57, 64, 71, and 78.

  Treatment repeats every 12 weeks for 2 years from the start of interim maintenance (for female patients) or 3 years from the start of interim maintenance (for male patients).

   [Note: *IT methotrexate is also given on day 29 of the first 4 courses of maintenance therapy.]

   [Note: **Oral methotrexate is held on day 29 of the first 4 courses of maintenance therapy (when IT methotrexate is given).]




• Radiotherapy: During the first course of maintenance therapy, patients with testicular disease undergo concurrent radiotherapy to the testes 5 days a week for 2.5 weeks (total dose 2400 cGy given in 12 daily fractions); patients with CNS3 disease undergo concurrent cranial radiotherapy 5 days a week for 2 weeks (total dose of 1800 cGy given in 10 daily fractions); and patients with T-cell ALL undergo concurrent cranial radiotherapy (total dose of 2400 cGy given in 10 daily fractions) 5 days a week for 2 weeks.

After completion of study treatment, patients are followed every 1-3 months for 3 years, and then every 6 months for 7 years.

Bleyer A: Older adolescents and young adults with acute lymphoblastic leukemia (ALL) in the United States: from the lowest to highest death rate and number of deaths--more rationale for the CALBG-SWOG-ECOG C10403 trial based on COG AALL0232. [Abstract] J Clin Oncol 26 (Suppl 15): A-18034, 2008.

Trial Contact Information

Trial Lead Organizations

Cancer and Leukemia Group B

Richard Larson, MD, Protocol chair		Ph: 773-702-6783; 888-824-0200
John Grecula, MD, Protocol co-chair		Ph: 614-293-8415

Eastern Cooperative Oncology Group

Selina Luger, MD, Protocol chair		Ph: 215-662-6348

Southwest Oncology Group

Anjali Advani, MD, Protocol chair		Ph: 216-445-9354; 800-862-7798 Email: advania@ccf.org

U.S.A.
Delaware
	Lewes
	Tunnell Cancer Center at Beebe Medical Center
		Clinical Trials Office - Tunnell Cancer Center	Ph:  302-645-3171
	Newark
	CCOP - Christiana Care Health Services
		Clinical Trial Office - CCOP - Christiana Care Health Services	Ph:  302-733-6227
Florida
	Orlando
	Florida Hospital Cancer Institute at Florida Hospital Orlando
		Clinical Trials Office - Florida Hospital Cancer Institute	Ph:  407-303-5623
Illinois
	Aurora
	Rush-Copley Cancer Care Center
		Kendrith Rowland, MD	Ph:  217-383-3010
	Bloomington
	St. Joseph Medical Center
		John Kugler, MD	Ph:  309-243-3000
	Canton
	Graham Hospital
		John Kugler, MD	Ph:  309-243-3000
	Carthage
	Memorial Hospital
		John Kugler, MD	Ph:  309-243-3000
	Chicago
	University of Chicago Cancer Research Center
		Clinical Trials Office - University of Chicago Cancer Research Center	Ph:  773-834-7424
	Eureka
	Eureka Community Hospital
		John Kugler, MD	Ph:  309-243-3000
	Galesburg
	Galesburg Clinic, PC
		John Kugler, MD	Ph:  309-243-3000
	Galesburg Cottage Hospital
		John Kugler, MD	Ph:  309-243-3000
	Havana
	Mason District Hospital
		John Kugler, MD	Ph:  309-243-3000
	Hopedale
	Hopedale Medical Complex
		John Kugler, MD	Ph:  309-243-3000
	Joliet
	Joliet Oncology-Hematology Associates, Limited - West
		Kendrith Rowland, MD	Ph:  217-383-3010
	Macomb
	McDonough District Hospital
		John Kugler, MD	Ph:  309-243-3000
	Normal
	BroMenn Regional Medical Center
		John Kugler, MD	Ph:  309-243-3000
	Community Cancer Center
		John Kugler, MD	Ph:  309-243-3000
	Ottawa
	Community Hospital of Ottawa
		John Kugler, MD	Ph:  309-243-3000
	Oncology Hematology Associates of Central Illinois, PC - Ottawa
		John Kugler, MD	Ph:  309-243-3000
	Pekin
	Cancer Treatment Center at Pekin Hospital
		John Kugler, MD	Ph:  309-243-3000
	Peoria
	CCOP - Illinois Oncology Research Association
		John Kugler, MD	Ph:  309-243-3000
	Methodist Medical Center of Illinois
		Clinical Trials Office - Methodist Medical Center of Illinois	Ph:  309-243-3000
	Oncology Hematology Associates of Central Illinois, PC - Peoria
		John Kugler, MD	Ph:  309-243-3000
	OSF St. Francis Medical Center
		John Kugler, MD	Ph:  309-243-3000
	Proctor Hospital
		John Kugler, MD	Ph:  309-243-3000
	Peru
	Illinois Valley Community Hospital
		John Kugler, MD	Ph:  309-243-3000
	Princeton
	Perry Memorial Hospital
		John Kugler, MD	Ph:  309-243-3000
	Spring Valley
	St. Margaret's Hospital
		John Kugler, MD	Ph:  309-243-3000
	Urbana
	Carle Cancer Center at Carle Foundation Hospital
		Clinical Trials Office - Carle Cancer Center	Ph:  800-446-5532
	CCOP - Carle Cancer Center
		Clinical Trials Office - CCOP - Carle Cancer Center	Ph:  800-446-5532
Indiana
	Beech Grove
	St. Francis Hospital and Health Centers - Beech Grove Campus
		Howard Gross, MD	Ph:  317-787-3311
	Fort Wayne
	Fort Wayne Medical Oncology and Hematology
		Sreenivasa Nattam, MD	Ph:  260-484-8830 800-852-2333
	Michigan City
	Saint Anthony Memorial Health Centers
		Kendrith Rowland, MD	Ph:  217-383-3010
	Richmond
	Reid Hospital & Health Care Services
		Howard Gross, MD	Ph:  765-983-3000
Kansas
	Chanute
	Cancer Center of Kansas, PA - Chanute
		Shaker Dakhil, MD, FACP	Ph:  316-262-4467
	Dodge City
	Cancer Center of Kansas, PA - Dodge City
		Shaker Dakhil, MD, FACP	Ph:  316-262-4467
	El Dorado
	Cancer Center of Kansas, PA - El Dorado
		Shaker Dakhil, MD, FACP	Ph:  316-262-4467
	Independence
	Cancer Center of Kansas-Independence
		Shaker Dakhil, MD, FACP	Ph:  316-262-4467
	Kingman
	Cancer Center of Kansas, PA - Kingman
		Shaker Dakhil, MD, FACP	Ph:  316-262-4467
	Liberal
	Southwest Medical Center
		Shaker Dakhil, MD, FACP	Ph:  316-262-4467
	Newton
	Cancer Center of Kansas, PA - Newton
		Shaker Dakhil, MD, FACP	Ph:  316-262-4467
	Parsons
	Cancer Center of Kansas, PA - Parsons
		Shaker Dakhil, MD, FACP	Ph:  316-262-4467
	Pratt
	Cancer Center of Kansas, PA - Pratt
		Shaker Dakhil, MD, FACP	Ph:  316-262-4467
	Salina
	Cancer Center of Kansas, PA - Salina
		Shaker Dakhil, MD, FACP	Ph:  316-262-4467
	Topeka
	Cotton-O'Neil Cancer Center
		Clinical Trials Office - Cotton-O'Neil Cancer Center	Ph:  785-270-4963
	Wellington
	Cancer Center of Kansas, PA - Wellington
		Shaker Dakhil, MD, FACP	Ph:  316-262-4467
	Wichita
	Associates in Womens Health, PA - North Review
		Shaker Dakhil, MD, FACP	Ph:  316-262-4467
	Cancer Center of Kansas, PA - Wichita
		Shaker Dakhil, MD, FACP	Ph:  316-262-4467
	Cancer Center of Kansas, PA - Medical Arts Tower
		Shaker Dakhil, MD, FACP	Ph:  316-262-4467
	CCOP - Wichita
		Shaker Dakhil, MD, FACP	Ph:  316-262-4467
	Via Christi Cancer Center at Via Christi Regional Medical Center
		Shaker Dakhil, MD, FACP	Ph:  316-262-4467
	Winfield
	Cancer Center of Kansas, PA - Winfield
		Shaker Dakhil, MD, FACP	Ph:  316-262-4467
Maryland
	Baltimore
	Greenebaum Cancer Center at University of Maryland Medical Center
		Clinical Trials Office - Greenebaum Cancer Center at University of Maryladn Medical Center	Ph:  800-888-8823
	Elkton MD
	Union Hospital Cancer Program at Union Hospital
		Stephen Grubbs, MD	Ph:  410-398-4000
Missouri
	Columbia
	Ellis Fischel Cancer Center at University of Missouri - Columbia
		Clinical Trial Office - Ellis Fischel Cancer Center	Ph:  573-882-4894
	Saint Louis
	Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis
		Ravi Vij, MD	Ph:  314-747-7222 800-600-3606
Montana
	Billings
	Billings Clinic - Downtown
		Clinical Trials Office - Billings Clinic - Downtown	Ph:  800-996-2663
			Email: research@billingsclinic.org
	CCOP - Montana Cancer Consortium
		Benjamin Marchello, MD	Ph:  406-259-2245 800-361-3239
	Hematology-Oncology Centers of the Northern Rockies - Billings
		Benjamin Marchello, MD	Ph:  406-238-6290 800-648-6274
	Northern Rockies Radiation Oncology Center
		Benjamin Marchello, MD	Ph:  406-248-2212 800-358-8818
	St. Vincent Healthcare Cancer Care Services
		Benjamin Marchello, MD	Ph:  406-657-7000
	Bozeman
	Bozeman Deaconess Cancer Center
		Benjamin Marchello, MD	Ph:  406-585-5070
	Butte
	St. James Healthcare Cancer Care
		Benjamin Marchello, MD	Ph:  406-723-2500
	Great Falls
		Benjamin Marchello, MD
	Great Falls Clinic - Main Facility
		Benjamin Marchello, MD	Ph:  406-454-2171 800-421-1649
	Helena
	St. Peter's Hospital
		Benjamin Marchello, MD	Ph:  406-442-2480
	Kalispell
	Glacier Oncology, PLLC
		Benjamin Marchello, MD	Ph:  406-752-7600
	Kalispell Medical Oncology at KRMC
		Benjamin Marchello, MD	Ph:  406-752-8900
	Kalispell Regional Medical Center
		Benjamin Marchello, MD	Ph:  406-752-5111
	Missoula
	Community Medical Center
		Benjamin Marchello, MD	Ph:  406-728-4100
	Guardian Oncology and Center for Wellness
		Benjamin Marchello, MD	Ph:  406-721-1118
	Montana Cancer Center at St. Patrick Hospital and Health Sciences Center
		Clinical Trials Office - Montana Cancer Center at St. Patrick Hospital and Health Sciences Center	Ph:  406-329-7029
	Montana Cancer Specialists at Montana Cancer Center
		Clinical Trials Office - Montana Cancer Specialists at Montana Cancer Center	Ph:  406-238-6962
New Jersey
	Voorhees
	Cancer Institute of New Jersey at Cooper - Voorhees
		Clinical Trials Office - Cancer Institute of New Jersey at Cooper University Hospital - Voorhees	Ph:  856-325-6757
New York
	Buffalo
	Roswell Park Cancer Institute
		Clinical Trials Office - Roswell Park Cancer Institute	Ph:  877-275-7724
	Lake Success
	Long Island Radiation Therapy - Lake Success
		Jonathan Kolitz, MD	Ph:  516-562-8970
	Manhasset
	CCOP - North Shore University Hospital
		Jonathan Kolitz, MD	Ph:  516-562-8970
	Don Monti Comprehensive Cancer Center at North Shore University Hospital
		Clinical Trials Office - Don Monti Comprehensive Cancer Center at North Shore University Hospital	Ph:  516-734-8900
	New Hyde Park
	Long Island Jewish Medical Center
		Jonathan Kolitz, MD	Ph:  516-562-8970
	New York
	New York Weill Cornell Cancer Center at Cornell University
		Clinical Trials Office - New York Weill Cornell Cancer Center at Cornell University	Ph:  212-746-1848
North Carolina
	Chapel Hill
	Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill
		Clinical Trials Office - Lineberger Comprehensive Cancer Center	Ph:  877-668-0683; 919-966-4432
	Goldsboro
	Wayne Memorial Hospital, Incorporated
		James Atkins, MD	Ph:  919-580-0000
	Winston-Salem
	Wake Forest University Comprehensive Cancer Center
		Clinical Trials Office - Wake Forest University Comprehensive Cancer Center	Ph:  336-713-6771
Ohio