Comparison of Different Combination Chemotherapy Regimens in Treating Children With Acute Lymphoblastic Leukemia

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ClinicalTrials.gov Identifier: NCT00005945

Recruitment Status : Completed

First Posted : January 27, 2003

Last Update Posted : February 23, 2016

Sponsor:

Collaborator:

National Cancer Institute (NCI)

Information provided by (Responsible Party):

Children's Oncology Group

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 more than one drug may kill more cancer cells. It is not yet known which combination chemotherapy regimen is more effective in treating childhood acute lymphoblastic leukemia.

PURPOSE: This randomized phase III trial is comparing different combination chemotherapy regimens to see how well they work in treating children with acute lymphoblastic leukemia.

Condition or disease	Intervention/treatment	Phase
Leukemia	Drug: cyclophosphamide Drug: cytarabine Drug: daunorubicin hydrochloride Drug: dexamethasone Drug: doxorubicin hydrochloride Drug: mercaptopurine Drug: methotrexate Drug: pegaspargase Drug: thioguanine Drug: vincristine sulfate Radiation: radiation therapy	Phase 3

Show detailed description

Detailed Description:

OBJECTIVES:

Compare the event-free survival and overall survival of children with standard-risk acute lymphoblastic leukemia treated with escalating-dose IV methotrexate without leucovorin calcium versus oral methotrexate during the interim maintenance phase of therapy.
Compare the event-free survival and overall survival of these patients after receiving treatment in two delayed intensification phases versus one delayed intensification phase.
Compare the toxic effects of oral versus escalating-dose intravenous methotrexate in these patients.
Determine the prognostic significance of the rate of disappearance of peripheral lymphoblasts and lymphocytes during the first week of treatment in these patients.
Determine the prognostic significance of trisomies of chromosomes 4, 5, 10, and 17 and early treatment response in patients treated with these regimens.
Determine the prognostic significance of the TEL-AML1 fusion transcript and early treatment response in patients treated with these regimens.
Determine the minimal residual disease (MRD) by polymerase chain reaction in bone marrow and cerebrospinal fluid at various stages of therapy in these patients.
Determine the prognostic significance of MRD during various stages of therapy in these patients.
Determine whether a second delayed intensification therapy improves the prognosis of patients who have MRD at the end of induction therapy.

OUTLINE: This is a randomized, multicenter study. Patients without CNS disease at diagnosis, achieving a specified early marrow response profile and M1 marrow status of less than 5% blasts in the bone marrow (regardless of the proportion of mature lymphocytes) by day 28 of induction therapy, and remaining event free with favorable bone marrow status and cytogenetics between day 21 and 28 of consolidation therapy are randomized to one of four treatment arms. Patients with CNS disease at diagnosis are assigned to treatment arm II and undergo cranial irradiation. Patients with any of the following unfavorable bone marrow features and/or unfavorable cytogenetic features are assigned to the augmented treatment regimen by day 21 of induction chemotherapy or at the beginning of consolidation chemotherapy:

NOTE: All T-cell precursor patients that are not more than 4 months past completion of the delayed intensification phase of therapy should be switched to the augmented regimen as of 3/8/2004. These patients may be switched to the augmented regimen. The protocol gives specific instructions according to the phase of therapy the patients are actually in.

Unfavorable marrow status:
- M2: 5-25% blasts in bone marrow at day 28 of induction chemotherapy (or at day 14 of induction chemotherapy if day 7 status is M3) OR
- M3: More than 25% blast cell in bone marrow, regardless of the proportion of mature lymphocytes at day 14 of induction chemotherapy
Unfavorable cytogenetics: Must have 1 of the following:
- t(9;22)(q34;q11)
- t(4;11)(q21;q23)
- Balanced t(1;19)(q23;p13)
- Hypodiploidy with less than 45 chromosomes
- Other 11q23 translocations involving MLL Patients receive standard induction chemotherapy comprising cytarabine (ARA-C) intrathecally (IT) on day 0 or up to 72 hours before day 0; oral dexamethasone (DM) twice daily on days 0-27; vincristine (VCR) IV on days 0, 7, 14, and 21; and pegaspargase (PEG-ASP) intramuscularly (IM) once between days 3-5. Patients without CNS disease at diagnosis receive methotrexate (MTX) IT on days 7 and 28. Patients with CNS disease at diagnosis receive MTX IT on days 7, 14, 21, and 28.

Patients who have achieved M1 marrow status by day 28 of induction therapy and have favorable early bone marrow response and cytogenetics proceed to standard consolidation therapy once blood counts have recovered. Patients with M3 bone marrow status at day 28 of induction therapy are taken off the protocol. All other patients are assigned to the augmented treatment regimen.

Beginning on day 28 of induction chemotherapy, patients receive standard consolidation chemotherapy comprising VCR IV on day 0 and oral mercaptopurine (MP) on days 0-27. Patients without CNS disease at diagnosis receive MTX IT on days 7, 14, 21, and 28. Patients with CNS disease at diagnosis receive MTX IT on day 7 and cranial irradiation 5 days a week for 2 weeks. Patients with testicular disease receive bilateral testicular radiotherapy 5 days a week for 1 week and then for 3 consecutive days during the next week.

NOTE: As of 3/8/2004, patients with T-cell disease who did not achieve M1 marrow status by day 14 of induction OR who did not receive augmented induction and/or consolidation (regardless of early marrow status) receive cranial irradiation.

Arm I: Beginning on day 28 of consolidation chemotherapy, patients receive interim maintenance I chemotherapy comprising oral DM twice daily on days 0-4 and 28-32; VCR IV on days 0 and 28; oral MTX on days 0, 7, 14, 21, 28, 35, 42, and 49; oral MP on days 0-49; and MTX IT on day 28.

Beginning on day 56 of interim maintenance I chemotherapy, patients receive delayed intensification chemotherapy comprising oral DM twice daily on days 0-6 and 14-20; VCR IV and doxorubicin (DOX) IV over 15 minutes to 2 hours on days 0, 7, and 14; PEG-ASP IM on day 3; cyclophosphamide (CTX) IV over 20-30 minutes on day 28; oral thioguanine (TG) on days 28-41; ARA-C IV or subcutaneously (SC) daily on days 28-31 and 35-38; and MTX IT on days 0 and 28.

Beginning on day 56 of delayed intensification chemotherapy, patients receive interim maintenance II chemotherapy identical to interim maintenance I chemotherapy except patients receive MTX IT on days 0 and 28.

Beginning on day 56 of interim maintenance II chemotherapy, patients receive maintenance chemotherapy comprising oral DM twice daily on days 0-4, 28-32, and 56-60; VCR IV on days 0, 28, and 56; oral MP on days 0-83; oral MTX on days 7, 14, 21, 28, 35, 42, 49, 56, 63, 70, and 77; and MTX IT on day 0.

Arm II: Patients receive interim maintenance I chemotherapy, delayed intensification chemotherapy, and interim maintenance II chemotherapy as in arm I. Beginning on day 56 of interim maintenance II chemotherapy, patients then receive a second course of delayed intensification chemotherapy followed by maintenance chemotherapy as in arm I.
Arm III: Beginning on day 28 of consolidation chemotherapy, patients receive interim maintenance I chemotherapy comprising VCR IV; escalating doses of MTX IV on days 0, 10, 20, 30, and 40; and MTX IT on day 30. Patients then receive delayed intensification chemotherapy as in arm I. Patients receive interim maintenance II chemotherapy as in interim maintenance I chemotherapy, but with IV MTX starting at 2/3 of the maximum tolerated dose (MTD) attained in interim maintenance I chemotherapy. Patients then receive maintenance chemotherapy as in arm I.
Arm IV: Patients receive interim maintenance I chemotherapy as in arm III, delayed intensification chemotherapy as in arm I, interim maintenance II chemotherapy as in arm III, delayed intensification II chemotherapy as in arm II, and maintenance chemotherapy as in arm I.
Augmented Treatment: Patients receive induction chemotherapy comprising daunorubicin IV continuously for 48 hours beginning no later than day 21; oral DM twice daily on days 14-27; and VCR IV on days 14 and 21. Patients without CNS disease at diagnosis receive MTX IT on days 21 and 35. Patients with CNS disease at diagnosis receive MTX IT on days 21 and 28.

NOTE: Patients with T-cell disease should re-start with augmented consolidation and proceed as per the augmented regimen.

Beginning on day 35 of induction chemotherapy, patients receive consolidation therapy comprising CTX IV over 20-30 minutes on days 0 and 28; oral MP on days 0-13 and 28-41; ARA-C IV or SC daily on days 0-3, 7-10, 28-31, and 35-38; VCR IV on days 14, 21, 42, and 49; and PEG-ASP IM on days 14 and 42. Patients without CNS disease at diagnosis receive MTX IT on days 7, 14, and 21. Patients with CNS disease at diagnosis receive MTX IT on day 7 and cranial irradiation as in the randomized treatment section. Patients with testicular leukemia receive radiotherapy as in the randomized treatment section.

Beginning on day 63 of consolidation chemotherapy, patients receive interim maintenance I chemotherapy comprising VCR IV on days 0, 10, 20, 30, and 40; escalating doses of MTX IV on days 10, 20, 30, and 40; PEG-ASP IM on days 1 and 21; and MTX IT on days 0 and 30.

Beginning on day 56 of interim maintenance I chemotherapy, patients receive delayed intensification I chemotherapy comprising oral DM twice daily on days 0-6 and 14-20; VCR IV on days 0, 7, 14, 42, and 49; DOX IV over 15 minutes to 2 hours on days 0, 7, and 14; PEG-ASP IM on days 3 and 42; CTX IV over 20-30 minutes on day 28; oral TG on days 28-41; ARA-C IV or SC daily on days 28-31 and 35-38; and MTX IT on days 0 and 28.

NOTE: Patients with T-cell disease who are in interim maintenance I chemotherapy with escalating IV methotrexate should continue this phase and then proceed as per the augmented regimen. If these patients are receiving conventional interim maintenance chemotherapy with oral methotrexate, they should stop and restart the interim maintenance as per the augmented regimen. These patients receive cranial irradiation starting on day 28 of delayed intensification II chemotherapy.

Beginning on day 56 of delayed intensification I chemotherapy, patients receive interim maintenance II chemotherapy as in interim maintenance I chemotherapy, but with IV MTX starting at 2/3 of the MTD attained in interim maintenance I chemotherapy.

NOTE: Patients with T-cell disease who are in delayed intensification I chemotherapy proceed with this phase, with the addition of 2 vincristine doses on days 42 and 49 and PEG-ASP on day 42. These patients then proceed as per the augmented regimen with the addition of cranial irradiation starting on day 28 of delayed intensification II chemotherapy.

NOTE: Patients with T-cell disease who are within 4 months of completing delayed intensification I chemotherapy and have not received interim maintenance II chemotherapy with escalating IV methotrexate or delayed intensification II chemotherapy receive a course of interim maintenance chemotherapy and delayed intensification II chemotherapy according to the augmented regimen. If these patients have received interim maintenance II chemotherapy with escalating IV methotrexate, they receive delayed intensification II chemotherapy according to the augmented regimen. These patients also receive cranial irradiation starting on day 28 of delayed intensification II chemotherapy and then proceed to maintenance therapy.

Beginning on day 56 of interim maintenance II chemotherapy, patients receive delayed intensification II chemotherapy as in delayed intensification I chemotherapy.

Beginning on day 56 of delayed intensification II chemotherapy, patients receive maintenance chemotherapy comprising oral DM twice daily on days 0-4, 28-32, and 56-60; VCR IV on days 0, 28, and 56; oral MP on days 0-83; oral MTX on days 7, 14, 21, 28, 35, 42, 49, 56, 63, 70, and 77; and MTX IT on day 0.

Patients are followed every 4-8 weeks for one year, every 3 months for one year, every 6 months for one year, and then annually thereafter.

PROJECTED ACCRUAL: A total of 2,037 randomized patients will be accrued for this study within 3.75 years.

Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	3054 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	None (Open Label)
Primary Purpose:	Treatment
Official Title:	Escalating Dose Intravenous Methotrexate Without Leucovorin Rescue Versus Oral Methotrexate and Single Versus Double Delayed Intensification for Children With Standard Risk Acute Lymphoblastic Leukemia
Study Start Date :	June 2000
Actual Primary Completion Date :	November 2007
Actual Study Completion Date :	June 2008

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Chronic Lymphocytic Leukemia Leukemia

Genetic and Rare Diseases Information Center resources: Acute Lymphoblastic Leukemia Lymphoblastic Lymphoma Childhood Acute Lymphoblastic Leukemia Lymphosarcoma

U.S. FDA Resources

Arms and Interventions

Arm	Intervention/treatment
Experimental: Induction Not Randomized Standard Induction (28 Days). M3 Marrow at Day 28 and Off Protocol Therapy.	Drug: cyclophosphamide Given IV Other Names: Cytoxan NSC-26271 Drug: dexamethasone Given PO Other Names: Decadron DM NSC-34521 Drug: methotrexate Given PO and IT Other Name: MTX Drug: pegaspargase Given IM Other Names: PEG-asparaginase Oncaspar L-asparaginase with polyethylene glycol Drug: vincristine sulfate Given IV Other Names: Oncovin NSC-67574 VCR
Experimental: Induction and Oral MTX, Double Delayed Intensification CNS Patients with CNS disease at diagnosis, without other unfavorable characteristics. Standard Induction (28 Days). Consolidation (28 days) and in remission Day 21 and at time of randomization, Interim maintenance I (2 months), Delayed intensification I (2 months), Interim maintenance II (2 months), Delayed intensification II (2 months), then Maintenance (12 week cycles). Cranial radiation therapy during the Consolidation phase.	Drug: cyclophosphamide Given IV Other Names: Cytoxan NSC-26271 Drug: cytarabine Given IT Other Names: Cytosine Arabinoside Ara_C Cytosar-U NSC-63878 Drug: dexamethasone Given PO Other Names: Decadron DM NSC-34521 Drug: doxorubicin hydrochloride Dose 25 g/m² IV Days 0, 7, 14, given over a period of 15 minutes to 2 hours Other Names: Adriamycin NSC-123127 Drug: mercaptopurine Given PO Other Name: 6-MP Drug: methotrexate Given PO and IT Other Name: MTX Drug: pegaspargase Given IM Other Names: PEG-asparaginase Oncaspar L-asparaginase with polyethylene glycol Drug: thioguanine Given PO Other Names: 6 TG NSC-752 Drug: vincristine sulfate Given IV Other Names: Oncovin NSC-67574 VCR Radiation: radiation therapy Undergo radiation therapy Other Names: irradiation radiotherapy therapy radiation
Experimental: Induction and Augmented regimen (IV MTX, Double DI) Patients with unfavorable characteristics. Standard Induction (14 Days), Augmented Induction (Days 14-35), Consolidation (9 weeks), Interim Maintenance I (56 Days), Delayed Intensification I (2 months), Interim Maintenance II (2 months), Delayed Intensification II (2 months), then Maintenance (84 day courses).	Drug: cyclophosphamide Given IV Other Names: Cytoxan NSC-26271 Drug: cytarabine Given IT Other Names: Cytosine Arabinoside Ara_C Cytosar-U NSC-63878 Drug: daunorubicin hydrochloride Given IV Other Names: Cerubidine NSC-82151 Drug: dexamethasone Given PO Other Names: Decadron DM NSC-34521 Drug: doxorubicin hydrochloride Dose 25 g/m² IV Days 0, 7, 14, given over a period of 15 minutes to 2 hours Other Names: Adriamycin NSC-123127 Drug: mercaptopurine Given PO Other Name: 6-MP Drug: methotrexate Given PO and IT Other Name: MTX Drug: pegaspargase Given IM Other Names: PEG-asparaginase Oncaspar L-asparaginase with polyethylene glycol Drug: thioguanine Given PO Other Names: 6 TG NSC-752 Drug: vincristine sulfate Given IV Other Names: Oncovin NSC-67574 VCR Radiation: radiation therapy Undergo radiation therapy Other Names: irradiation radiotherapy therapy radiation
Experimental: Induction and Oral MTX, Single Delayed Intensification Patients without CNS disease at diagnosis, with favorable cytogenetics. Standard Induction (28 Days). Consolidation (28 days) and in remission Day 21 and at time of randomization, Interim maintenance I (2 months), Delayed intensification I (2 months), Interim maintenance II (2 months) then Maintenance (12 week cycles). Biopsy-proven testicular leukemia pts at diagnosis will receive testicular radiation therapy during the consolidation phase.	Drug: cyclophosphamide Given IV Other Names: Cytoxan NSC-26271 Drug: cytarabine Given IT Other Names: Cytosine Arabinoside Ara_C Cytosar-U NSC-63878 Drug: dexamethasone Given PO Other Names: Decadron DM NSC-34521 Drug: doxorubicin hydrochloride Dose 25 g/m² IV Days 0, 7, 14, given over a period of 15 minutes to 2 hours Other Names: Adriamycin NSC-123127 Drug: mercaptopurine Given PO Other Name: 6-MP Drug: methotrexate Given PO and IT Other Name: MTX Drug: pegaspargase Given IM Other Names: PEG-asparaginase Oncaspar L-asparaginase with polyethylene glycol Drug: thioguanine Given PO Other Names: 6 TG NSC-752 Drug: vincristine sulfate Given IV Other Names: Oncovin NSC-67574 VCR Radiation: radiation therapy Undergo radiation therapy Other Names: irradiation radiotherapy therapy radiation
Experimental: Induction and Oral MTX, Double Delayed Intensification Patients without CNS disease at diagnosis, with favorable cytogenetics. Standard Induction (28 Days). Consolidation (28 days) and in remission Day 21 and at time of randomization, Interim maintenance I (2 months), Delayed intensification I (2 months), Interim maintenance II (2 months), Delayed intensification II (2 months), then Maintenance (12 week cycles). Biopsy-proven testicular leukemia pts at diagnosis will receive testicular radiation therapy during the consolidation phase.	Drug: cyclophosphamide Given IV Other Names: Cytoxan NSC-26271 Drug: cytarabine Given IT Other Names: Cytosine Arabinoside Ara_C Cytosar-U NSC-63878 Drug: dexamethasone Given PO Other Names: Decadron DM NSC-34521 Drug: doxorubicin hydrochloride Dose 25 g/m² IV Days 0, 7, 14, given over a period of 15 minutes to 2 hours Other Names: Adriamycin NSC-123127 Drug: mercaptopurine Given PO Other Name: 6-MP Drug: methotrexate Given PO and IT Other Name: MTX Drug: pegaspargase Given IM Other Names: PEG-asparaginase Oncaspar L-asparaginase with polyethylene glycol Drug: thioguanine Given PO Other Names: 6 TG NSC-752 Drug: vincristine sulfate Given IV Other Names: Oncovin NSC-67574 VCR Radiation: radiation therapy Undergo radiation therapy Other Names: irradiation radiotherapy therapy radiation
Experimental: Induction and IV MTX, Single Delayed Intensification Patients without CNS disease at diagnosis, with favorable cytogenetics. Standard Induction (28 Days). Consolidation (28 days) and in remission Day 21 and at time of randomization, Interim maintenance I (2 months), Delayed intensification I (2 months), Interim maintenance II (2 months) then Maintenance (12 week cycles). Biopsy-proven testicular leukemia pts at diagnosis will receive testicular radiation therapy during the consolidation phase.	Drug: cyclophosphamide Given IV Other Names: Cytoxan NSC-26271 Drug: cytarabine Given IT Other Names: Cytosine Arabinoside Ara_C Cytosar-U NSC-63878 Drug: dexamethasone Given PO Other Names: Decadron DM NSC-34521 Drug: doxorubicin hydrochloride Dose 25 g/m² IV Days 0, 7, 14, given over a period of 15 minutes to 2 hours Other Names: Adriamycin NSC-123127 Drug: mercaptopurine Given PO Other Name: 6-MP Drug: methotrexate Given PO and IT Other Name: MTX Drug: pegaspargase Given IM Other Names: PEG-asparaginase Oncaspar L-asparaginase with polyethylene glycol Drug: thioguanine Given PO Other Names: 6 TG NSC-752 Drug: vincristine sulfate Given IV Other Names: Oncovin NSC-67574 VCR Radiation: radiation therapy Undergo radiation therapy Other Names: irradiation radiotherapy therapy radiation
Experimental: Induction and IV MTX, Double Delayed Intensification Patients without CNS disease at diagnosis, with favorable cytogenetics. Standard Induction (28 Days). Consolidation (28 days) and in event free remission Day 21 and at time of randomization, Interim maintenance I (2 months), Delayed intensification I (2 months), Interim maintenance II (2 months), Delayed intensification II (2 months), then Maintenance (12 week cycles). Biopsy-proven testicular leukemia pts at diagnosis will receive testicular radiation therapy during the consolidation phase.	Drug: cyclophosphamide Given IV Other Names: Cytoxan NSC-26271 Drug: cytarabine Given IT Other Names: Cytosine Arabinoside Ara_C Cytosar-U NSC-63878 Drug: dexamethasone Given PO Other Names: Decadron DM NSC-34521 Drug: doxorubicin hydrochloride Dose 25 g/m² IV Days 0, 7, 14, given over a period of 15 minutes to 2 hours Other Names: Adriamycin NSC-123127 Drug: mercaptopurine Given PO Other Name: 6-MP Drug: methotrexate Given PO and IT Other Name: MTX Drug: pegaspargase Given IM Other Names: PEG-asparaginase Oncaspar L-asparaginase with polyethylene glycol Drug: thioguanine Given PO Other Names: 6 TG NSC-752 Drug: vincristine sulfate Given IV Other Names: Oncovin NSC-67574 VCR Radiation: radiation therapy Undergo radiation therapy Other Names: irradiation radiotherapy therapy radiation

Outcome Measures

Primary Outcome Measures :

Event Free Survival [ Time Frame: Time of randomization ]
The primary outcome index used in examining the randomized treatment groups will be event free survival (EFS) from the time of randomization (i.e., end of Consolidation), where the life table events will consist of the first occurrence of leukemic relapse at any site, death, or occurrence of a second malignancy.

Eligibility Criteria

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Ages Eligible for Study:	1 Year to 9 Years (Child)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

DISEASE CHARACTERISTICS:

Diagnosis of previously untreated B-cell precursor acute lymphoblastic leukemia
- More than 25% L1 or L2 lymphoblasts
- No more than 25% L3 lymphoblasts
- WBC < 50,000/mm^3
No T-cell precursor acute lymphoblastic leukemia by immunophenotyping
Massive lymphadenopathy, massive splenomegaly, or large mediastinal mass allowed
CNS or testicular leukemia allowed
No patients found to have t(8;14)(q24;q32), t(8;22)(q24;q11), and t(2;8)(p11-p12;q24) (characteristic of Burkitt's lymphoma)

PATIENT CHARACTERISTICS:

Age:

1 to 9

Performance status:

Not specified

Life expectancy:

Not specified

Hematopoietic:

See Disease Characteristics

Hepatic:

Not specified

Renal:

Not specified

Other:

Not pregnant
Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy:

Not specified

Chemotherapy:

No more than 72 hours since prior intrathecal cytarabine

Endocrine therapy:

At least 30 days since prior systemic corticosteroids given for more than 48 hours
Prior corticosteroids for mediastinal mass causing superior mediastinal syndrome allowed
Prior or concurrent inhaled corticosteroids allowed

Radiotherapy:

Prior radiotherapy for mediastinal mass causing superior mediastinal syndrome allowed
No concurrent spinal radiotherapy

Surgery:

Not specified

Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00005945

Locations

Show 130 study locations

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United States, Arizona
Phoenix Children's Hospital
Phoenix, Arizona, United States, 85016
United States, California
Southern California Permanente Medical Group
Downey, California, United States, 90242
City of Hope Comprehensive Cancer Center
Duarte, California, United States, 91010-3000
Loma Linda University Cancer Institute at Loma Linda University Medical Center
Loma Linda, California, United States, 92354
Children's Hospital Los Angeles
Los Angeles, California, United States, 90027-0700
Samuel Oschin Comprehensive Cancer Institute at Cedars-Sinai Medical Center
Los Angeles, California, United States, 90048
Jonsson Comprehensive Cancer Center, UCLA
Los Angeles, California, United States, 90095-1781
Children's Hospital Central California
Madera, California, United States, 93638-8762
Children's Hospital and Research Center at Oakland
Oakland, California, United States, 94609-1809
Chao Family Comprehensive Cancer Center at University of California Irvine Medical Center
Orange, California, United States, 92868
Children's Hospital of Orange County
Orange, California, United States, 92868
Kaiser Permanente Medical Center - Sacramento
Sacramento, California, United States, 95825
Kaiser Permanente Medical Center/Kaiser Foundation Hospital - San Diego
San Diego, California, United States, 92120
UCSF Comprehensive Cancer Center
San Francisco, California, United States, 94143
Santa Barbara Cottage Hospital
Santa Barbara, California, United States, 93102
Kaiser Permanente Medical Center - Santa Clara
Santa Clara, California, United States, 95051-5386
General Robert Huyser Cancer Center at David Grant Medical Center
Travis Air Force Base, California, United States, 94535
United States, Colorado
Children's Hospital Cancer Center
Denver, Colorado, United States, 80218
Presbyterian - St. Luke's Medical Center
Denver, Colorado, United States, 80218
United States, Connecticut
Carole and Ray Neag Comprehensive Cancer Center at the University of Connecticut Health Center
Farmington, Connecticut, United States, 06360-7106
Yale Comprehensive Cancer Center
New Haven, Connecticut, United States, 06520-8064
United States, Delaware
Alfred I. duPont Hospital for Children
Wilmington, Delaware, United States, 19899
United States, District of Columbia
Lombardi Cancer Center at Georgetown University Medical Center
Washington, District of Columbia, United States, 20007
Children's National Medical Center
Washington, District of Columbia, United States, 20010-2970
United States, Georgia
AFLAC Cancer Center and Blood Disorders Service of Children's Healthcare of Atlanta - Scottish Rite Campus
Atlanta, Georgia, United States, 30342
Medical Center of Central Georgia
Macon, Georgia, United States, 31201
Curtis & Elizabeth Anderson Cancer Institute at Memorial Health University Medical Center
Savannah, Georgia, United States, 31405
United States, Idaho
Mountain States Tumor Institute - Boise
Boise, Idaho, United States, 83712
United States, Illinois
University of Chicago Cancer Research Center
Chicago, Illinois, United States, 60601
University of Illinois Medical Center
Chicago, Illinois, United States, 60612
Lutheran General Cancer Care Center
Park Ridge, Illinois, United States, 60068-1174
Southern Illinois University School of Medicine
Springfield, Illinois, United States, 62794-9658
United States, Indiana
Riley Children Cancer Center at Riley Hospital for Children
Indianapolis, Indiana, United States, 46202-5225
United States, Iowa
Blank Children's Hospital
Des Moines, Iowa, United States, 50308
Holden Comprehensive Cancer Center at University of Iowa
Iowa City, Iowa, United States, 52242-1009
United States, Kentucky
Markey Cancer Center at University of Kentucky Chandler Medical Center
Lexington, Kentucky, United States, 40536-0284
Kosair Children's Hospital
Louisville, Kentucky, United States, 40202-3830
United States, Louisiana
MBCCOP - LSU Health Sciences Center
New Orleans, Louisiana, United States, 70112
United States, Maryland
Alvin and Lois Lapidus Cancer Institute at Sinai Hospital
Baltimore, Maryland, United States, 21215
United States, Massachusetts
Baystate Regional Cancer Program at D'Amour Center for Cancer Care
Springfield, Massachusetts, United States, 01107
United States, Michigan
University of Michigan Comprehensive Cancer Center
Ann Arbor, Michigan, United States, 48109-0914
Josephine Ford Cancer Center at Henry Ford Health System
Detroit, Michigan, United States, 48202
DeVos Children's Hospital
Grand Rapids, Michigan, United States, 49503
Bronson Methodist Hospital
Kalamazoo, Michigan, United States, 49007-5364
Breslin Cancer Center at Ingham Regional Medical Center
Lansing, Michigan, United States, 48910
CCOP - Beaumont
Royal Oak, Michigan, United States, 48073-6769
William Beaumont Hospital - Royal Oak
Royal Oak, Michigan, United States, 48073-6769
United States, Minnesota
St. Mary's - Duluth Clinic Cancer Center
Duluth, Minnesota, United States, 55805
Children's Hospitals and Clinics - Minneapolis/St. Paul
Minneapolis, Minnesota, United States, 55404
University of Minnesota Cancer Center
Minneapolis, Minnesota, United States, 55455
Mayo Clinic Cancer Center
Rochester, Minnesota, United States, 55905
United States, Missouri
Children's Mercy Hospital
Kansas City, Missouri, United States, 64108
United States, Nebraska
Children's Hospital of Omaha
Omaha, Nebraska, United States, 68114
UNMC Eppley Cancer Center at the University of Nebraska Medical Center
Omaha, Nebraska, United States, 68198-2168
United States, Nevada
Sunrise Hospital and Medical Center
Las Vegas, Nevada, United States, 89109
United States, New Jersey
St. Barnabas Medical Center
Livingston, New Jersey, United States, 07039
Cancer Institute of New Jersey at UMDNJ - Robert Wood Johnson Medical School
New Brunswick, New Jersey, United States, 08903
Newark Beth Israel Medical Center
Newark, New Jersey, United States, 07112-2094
St. Joseph's Hospital and Medical Center
Paterson, New Jersey, United States, 07503
Valerie Fund Children's Center at Atlantic Health
Summit, New Jersey, United States, 07901
United States, New York
Cancer Center of Albany Medical Center
Albany, New York, United States, 12208
Albert Einstein Cancer Center at Albert Einstein College of Medicine
Bronx, New York, United States, 10461
Brooklyn Hospital Center
Brooklyn, New York, United States, 11201-5493
SUNY Downstate Medical Center
Brooklyn, New York, United States, 11203
Brookdale University Hospital and Medical Center
Brooklyn, New York, United States, 11212
Comprehensive Cancer Center at Maimonides Medical Center
Brooklyn, New York, United States, 11219
Schneider Children's Hospital
New Hyde Park, New York, United States, 11042
Memorial Sloan-Kettering Cancer Center
New York, New York, United States, 10021
New York Weill Cornell Cancer Center at Cornell University
New York, New York, United States, 10021
Herbert Irving Comprehensive Cancer Center at Columbia University
New York, New York, United States, 10032
Long Island Cancer Center at Stony Brook University Hospital
Stony Brook, New York, United States, 11794
SUNY Upstate Medical University Hospital
Syracuse, New York, United States, 13210
New York Medical College
Valhalla, New York, United States, 10595
United States, North Carolina
Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill
Chapel Hill, North Carolina, United States, 27599
Blumenthal Cancer Center at Carolinas Medical Center
Charlotte, North Carolina, United States, 28232-2861
Presbyterian Cancer Center at Presbyterian Hospital
Charlotte, North Carolina, United States, 28233
United States, North Dakota
Dakota Cancer Institute at Innovis Health - Dakota Clinic
Fargo, North Dakota, United States, 58103-4940
Meritcare Roger Maris Cancer Center
Fargo, North Dakota, United States, 58122
United States, Ohio
Children's Hospital Medical Center of Akron
Akron, Ohio, United States, 44308-1062
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, United States, 45229-3039
Ireland Cancer Center at University Hospitals of Cleveland and Case Western Reserve University
Cleveland, Ohio, United States, 44106-5065
Columbus Children's Hospital
Columbus, Ohio, United States, 43205-2696
Children's Medical Center - Dayton
Dayton, Ohio, United States, 45404
Toledo Children's Hospital
Toledo, Ohio, United States, 43601
St. Vincent Mercy Medical Center
Toledo, Ohio, United States, 43608
United States, Oregon
CCOP - Columbia River Oncology Program
Portland, Oregon, United States, 97225
Doernbecher Children's Hospital at Oregon Health & Science University
Portland, Oregon, United States, 97239-3098
United States, Pennsylvania
Geisinger Medical Center
Danville, Pennsylvania, United States, 17822-1320
Children's Hospital at Milton S. Hershey Medical Center
Hershey, Pennsylvania, United States, 17033
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, United States, 19104
Children's Hospital of Pittsburgh
Pittsburgh, Pennsylvania, United States, 15213
United States, Rhode Island
Rhode Island Hospital
Providence, Rhode Island, United States, 02903
United States, South Dakota
Sioux Valley Hospital and University of South Dakota Medical Center
Sioux Falls, South Dakota, United States, 57117-5039
United States, Tennessee
East Tennessee State University Cancer Center at Johnson City Medical Center
Johnson City, Tennessee, United States, 37614-0622
East Tennessee Children's Hospital
Knoxville, Tennessee, United States, 37901
Vanderbilt Children's Hospital
Nashville, Tennessee, United States, 37232-6310
United States, Texas
Texas Tech University Health Sciences Center School of Medicine
Amarillo, Texas, United States, 79106
Children's Hospital of Austin
Austin, Texas, United States, 78701
Medical City Dallas Hospital
Dallas, Texas, United States, 75230
MD Anderson Cancer Center at University of Texas
Houston, Texas, United States, 77030-4009
Covenant Children's Hospital
Lubbock, Texas, United States, 79410
MBCCOP - South Texas Pediatrics
San Antonio, Texas, United States, 78229-3900
Methodist Cancer Center at Methodist Specialty and Transplant Hospital
San Antonio, Texas, United States, 78229-3902
CCOP - Scott and White Hospital
Temple, Texas, United States, 76508
United States, Virginia
Children's Hospital of the King's Daughters
Norfolk, Virginia, United States, 23507
United States, Washington
Children's Hospital and Regional Medical Center - Seattle
Seattle, Washington, United States, 98105
Group Health Central Hospital
Seattle, Washington, United States, 98112
Deaconess Medical Center
Spokane, Washington, United States, 99210-0248
Mary Bridge Children's Hospital and Health Center
Tacoma, Washington, United States, 98415-0299
United States, West Virginia
West Virginia University - Robert C. Byrd Health Sciences Center - Charleston Division
Charleston, West Virginia, United States, 25302
Cabell Huntington Hospital
Huntington, West Virginia, United States, 25701
United States, Wisconsin
Bellin Memorial Hospital
Green Bay, Wisconsin, United States, 54301
Gundersen Lutheran Cancer Center at Gundersen Lutheran Medical Center
La Crosse, Wisconsin, United States, 54601
University of Wisconsin Comprehensive Cancer Center
Madison, Wisconsin, United States, 53792-6164
Marshfield Clinic - Marshfield Center
Marshfield, Wisconsin, United States, 54449-5772
CCOP - Marshfield Clinic Research Foundation
Marshfield, Wisconsin, United States, 54449
Australia, New South Wales
Sydney Children's Hospital
Randwick, New South Wales, Australia, 2031
Australia, Queensland
Royal Children's Hospital
Brisbane, Queensland, Australia, 4029
Australia, Western Australia
Princess Margaret Hospital for Children
Perth, Western Australia, Australia, 6001
Canada, British Columbia
British Columbia Children's Hospital
Vancouver, British Columbia, Canada, V6H 3V4
Canada, Manitoba
CancerCare Manitoba
Winnipeg, Manitoba, Canada, R3E 0V9
Canada, Newfoundland and Labrador
Janeway Children's Health and Rehabilitation Centre
St. John's, Newfoundland and Labrador, Canada, A1B 3V6
Canada, Nova Scotia
IWK Health Centre
Halifax, Nova Scotia, Canada, B3J 3G9
Canada, Ontario
Children's Hospital of Western Ontario
London, Ontario, Canada, N6C 2V5
Canada, Saskatchewan
Allan Blair Cancer Centre at Pasqua Hospital
Regina, Saskatchewan, Canada, S4T 7T1
Saskatoon Cancer Centre
Saskatoon, Saskatchewan, Canada, S7N 4H4
New Zealand
Starship Children's Health
Auckland, New Zealand
Switzerland
Swiss Pediatric Oncology Group Bern
Bern, Switzerland, CH 3010
Swiss Pediatric Oncology Group Geneva
Geneva, Switzerland, CH 1211
Swiss Pediatric Oncology Group Lausanne
Lausanne, Switzerland, CH 1011

Sponsors and Collaborators

Children's Oncology Group

National Cancer Institute (NCI)

Investigators

Layout table for investigator information

Study Chair:	Yousif H. Matloub, MD	University of Wisconsin, Madison

More Information

Publications of Results:

Matloub Y, Bostrom BC, Hunger SP, Stork LC, Angiolillo A, Sather H, La M, Gastier-Foster JM, Heerema NA, Sailer S, Buckley PJ, Thomson B, Cole C, Nachman JB, Reaman G, Winick N, Carroll WL, Devidas M, Gaynon PS. Escalating intravenous methotrexate improves event-free survival in children with standard-risk acute lymphoblastic leukemia: a report from the Children's Oncology Group. Blood. 2011 Jul 14;118(2):243-51. doi: 10.1182/blood-2010-12-322909. Epub 2011 May 11.

Matloub Y, Bostrom BC, Angiolillo AL, et al.: Children with NCI standard risk acute lymphoblastic leukemia (ALL) and TEL-AML1 or favorable chromosome trisomies are almost certain to be cured with graduated intensity therapy: results of the CCG - 1991 study. [Abstract] Blood 114 (22): A-320, 2009.

Matloub Y, Bostrom BC, Hunger SP, et al.: Escalating dose intravenous methotrexate without leucovorin rescue during interim maintenance is superior to oral methotrexate for children with standard risk acute lymphoblastic leukemia (SR-ALL): Children's Oncology Group study 1991. [Abstract] Blood 112 (11): A-9, 2008.

Matloub Y, Angiolillo A, Bostrom B, et al.: Double delayed intensification (DDI) is equivalent to single DI (SDI) in children with National Cancer Institute (NCI) standard-risk acute lymphoblastic leukemia (SR-ALL) treated on Children's Cancer Group (CCG) clinical trial 1991 (CCG-1991). [Abstract] Blood 108 (11): A-146, 2006.

Other Publications:

Bruggers CS, Moyer-Mileur LJ, Ransdall L: Body composition, bone mineral acquisition, and cardiovascular fitness in children with standard risk acute lymphoblastic leukemia: response to a home-based exercise and nutrition education program. [Abstract] 2006 Pediatric Academic Societies' Annual Meeting, April 29 - May 2, San Francisco, CA. A-3505.46, 2006.

Matloub Y, Asselin BL, Stork LC, et al.: Outcome of children with T-Cell acute lymphoblastic leukemia (T-ALL) and standard risk (SR) features: results of CCG-1952, CCG-1991 and POG 9404. [Abstract] Blood 104 (11): A-680, 195a, 2004.

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.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Matloub Y, Rabin KR, Ji L, Devidas M, Hitzler J, Xu X, Bostrom BC, Stork LC, Winick N, Gastier-Foster JM, Heerema NA, Stonerock E, Carroll WL, Hunger SP, Gaynon PS. Excellent long-term survival of children with Down syndrome and standard-risk ALL: a report from the Children's Oncology Group. Blood Adv. 2019 Jun 11;3(11):1647-1656. doi: 10.1182/bloodadvances.2019032094.

Layout table for additonal information

Responsible Party:	Children's Oncology Group
ClinicalTrials.gov Identifier:	NCT00005945
Other Study ID Numbers:	1991 CCG-1991 ( Other Identifier: Children's Cancer Group ) CDR0000067855 ( Other Identifier: Clinical Trials.gov ) NCI-2012-02333 ( Other Identifier: NCI ) U10CA098543 ( U.S. NIH Grant/Contract )
First Posted:	January 27, 2003 Key Record Dates
Last Update Posted:	February 23, 2016
Last Verified:	February 2016

Keywords provided by Children's Oncology Group:


untreated childhood acute lymphoblastic leukemia L1 childhood acute lymphoblastic leukemia L2 childhood acute lymphoblastic leukemia L3 childhood acute lymphoblastic leukemia

Additional relevant MeSH terms:

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Leukemia Precursor Cell Lymphoblastic Leukemia-Lymphoma Leukemia, Lymphoid Neoplasms by Histologic Type Neoplasms Lymphoproliferative Disorders Lymphatic Diseases Immunoproliferative Disorders Immune System Diseases Cytarabine Dexamethasone Cyclophosphamide Doxorubicin Liposomal doxorubicin Methotrexate	Vincristine Daunorubicin Asparaginase Mercaptopurine Thioguanine Pegaspargase Immunosuppressive Agents Immunologic Factors Physiological Effects of Drugs Antirheumatic Agents Antineoplastic Agents, Alkylating Alkylating Agents Molecular Mechanisms of Pharmacological Action Antineoplastic Agents Myeloablative Agonists

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