Combination Chemotherapy in Treating Children With Acute Lymphocytic Leukemia
This study has been completed.
Sponsor:
Children's Oncology Group
Collaborator:
Information provided by (Responsible Party):
Children's Oncology Group
ClinicalTrials.gov Identifier:
NCT00002812
First received: November 1, 1999
Last updated: August 23, 2013
Last verified: August 2013
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Purpose
RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Combining more than one drug and giving the drugs in different combinations may kill more cancer cells.
PURPOSE: Randomized phase III trial to compare the effectiveness of standard combination chemotherapy treatment with more intensive combination chemotherapy in treating children with acute lymphocytic leukemia.
| Condition | Intervention | Phase |
|---|---|---|
|
Leukemia |
Drug: asparaginase Drug: cyclophosphamide Drug: cytarabine Drug: daunorubicin hydrochloride Drug: dexamethasone Drug: doxorubicin hydrochloride Drug: idarubicin Drug: mercaptopurine Drug: methotrexate Drug: pegaspargase Drug: prednisone Drug: thioguanine Drug: vincristine sulfate Radiation: radiation therapy |
Phase 3 |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment |
| Official Title: | Treatment of Patients With Acute Lymphoblastic Leukemia With Unfavorable Features: A Phase III Group-wide Study |
Resource links provided by NLM:
Drug Information available for:
Dexamethasone
Cyclophosphamide
Mercaptopurine
Prednisone
Methotrexate
Cytarabine
Thioguanine
Vincristine sulfate
Asparaginase
Methotrexate sodium
Daunorubicin
Doxorubicin
Daunorubicin hydrochloride
Doxorubicin hydrochloride
Idarubicin hydrochloride
Idarubicin
Pegaspargase
Daunorubicin citrate
Asparaginase erwinia chrysanthemi
Genetic and Rare Diseases Information Center resources:
Acute Lymphoblastic Leukemia
Acute Lymphoblastic Leukemia, Childhood
Acute Monoblastic Leukemia
Acute Myeloblastic Leukemia Type 5
Children's Interstitial Lung Disease
Lymphosarcoma
U.S. FDA Resources
Further study details as provided by Children's Oncology Group:
Primary Outcome Measures:
- Event Free Survival [ Time Frame: from the time of randomization where the life table events will consist of the first occurrence of the following events: failure to achieve remission, leukemic relapse at any site, death, or occurrence of a second malignancy. ] [ Designated as safety issue: No ]The primary outcome index used in examining most of the randomized treatment groups will be event-free survival (EFS).
| Enrollment: | 2078 |
| Study Start Date: | September 1996 |
| Primary Completion Date: | March 2006 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Experimental: Arm A - Standard BFM of Standard Duration (RER)
Induction chemotherapy Days 0 - 7. Prednisone 60 mg/m² PO 4 x day. Vincristine sulfate 1.5 mg/m² IV push weekly x 2 Days 0 and 7. Daunomycin (daunorubicin hydrochloride) 25 mg/m² IV push (over 15 min.) weekly x 2 Days 0 and 7. IT Cytosine Arabinoside (cytarabine, Ara-C) Day 0. Asparaginase 6000 IU/m² IM x 3 Days 3, 5, and 7. Day 7 Bone Marrow. Consolidation (Phase II) (5 weeks) Prednisone Taper, cyclophosphamide, cytosine arabinoside (Ara-C), mercaptopurine, vincristine sulfate, pegaspargase, IT Methotrexate and radiation therapy.
|
Drug: asparaginase
Given IV
Other Names:
Drug: cyclophosphamide
Given IV
Other Names:
Drug: cytarabine
Given IV
Other Names:
Drug: daunorubicin hydrochloride
Given IV
Other Names:
Drug: dexamethasone
Given IV
Other Names:
Drug: doxorubicin hydrochloride
Given IV
Other Names:
Drug: idarubicin
Given IV
Other Names:
Drug: mercaptopurine
Given IV
Other Names:
Drug: methotrexate
Given PO
Other Name: NSC-740
Drug: pegaspargase
Given IV
Other Names:
Drug: prednisone
Given PO
Other Name: NSC-10023
Drug: thioguanine
Given IV
Other Names:
Drug: vincristine sulfate
Given IV
Other Names:
Radiation: radiation therapy
|
|
Experimental: Arm B - Standard BFM with Double Delayed Intensification (RER)
Induction chemotherapy Days 0 - 7. Prednisone 60 mg/m² PO 4 x day. Vincristine sulfate 1.5 mg/m² IV push weekly x 2 Days 0 and 7. Daunomycin (daunorubicin hydrochloride) 25 mg/m² IV push (over 15 min.) weekly x 2 Days 0 and 7. IT Cytosine Arabinoside (cytarabine, Ara-C) Day 0. Asparaginase 6000 IU/m² IM x 3 Days 3, 5, and 7. Day 7 Bone Marrow Consolidation (5 weeks) (Phase II) Prednisone Taper, cyclophosphamide, cytosine arabinoside (Ara-C), mercaptopurine, vincristine sulfate, pegaspargase, IT Methotrexate and radiation therapy.
|
Drug: asparaginase
Given IV
Other Names:
Drug: cyclophosphamide
Given IV
Other Names:
Drug: cytarabine
Given IV
Other Names:
Drug: daunorubicin hydrochloride
Given IV
Other Names:
Drug: dexamethasone
Given IV
Other Names:
Drug: doxorubicin hydrochloride
Given IV
Other Names:
Drug: idarubicin
Given IV
Other Names:
Drug: mercaptopurine
Given IV
Other Names:
Drug: methotrexate
Given PO
Other Name: NSC-740
Drug: pegaspargase
Given IV
Other Names:
Drug: prednisone
Given PO
Other Name: NSC-10023
Drug: thioguanine
Given IV
Other Names:
Drug: vincristine sulfate
Given IV
Other Names:
Radiation: radiation therapy
|
|
Experimental: Arm C - Augumented BFM of Standard Duration (RER)
Induction chemotherapy Days 0 - 7. Prednisone 60 mg/m² PO 4 x day. Vincristine sulfate 1.5 mg/m² IV push weekly x 2 Days 0 and 7. Daunomycin (daunorubicin hydrochloride) 25 mg/m² IV push (over 15 min.) weekly x 2 Days 0 and 7. IT Cytosine Arabinoside (cytarabine, Ara-C) Day 0. Asparaginase 6000 IU/m² IM x 3 Days 3, 5, and 7. Day 7 Bone Marrow Consolidation (9 weeks) (Phase II) Prednisone Taper, cyclophosphamide, cytosine arabinoside (Ara-C), mercaptopurine, vincristine sulfate, pegaspargase, IT Methotrexate and radiation therapy.
|
Drug: asparaginase
Given IV
Other Names:
Drug: cyclophosphamide
Given IV
Other Names:
Drug: cytarabine
Given IV
Other Names:
Drug: daunorubicin hydrochloride
Given IV
Other Names:
Drug: dexamethasone
Given IV
Other Names:
Drug: doxorubicin hydrochloride
Given IV
Other Names:
Drug: idarubicin
Given IV
Other Names:
Drug: mercaptopurine
Given IV
Other Names:
Drug: methotrexate
Given PO
Other Name: NSC-740
Drug: pegaspargase
Given IV
Other Names:
Drug: prednisone
Given PO
Other Name: NSC-10023
Drug: thioguanine
Given IV
Other Names:
Drug: vincristine sulfate
Given IV
Other Names:
Radiation: radiation therapy
|
|
Experimental: Arm D - Augmented BFM with Dbl Delayed Intensification (RER)
Induction chemotherapy Days 0 - 7. Prednisone 60 mg/m² PO 4 x day. Vincristine sulfate 1.5 mg/m² IV push weekly x 2 Days 0 and 7. Daunomycin (daunorubicin hydrochloride) 25 mg/m² IV push (over 15 min.) weekly x 2 Days 0 and 7. IT Cytosine Arabinoside (cytarabine, Ara-C) Day 0. Asparaginase 6000 IU/m² IM x 3 Days 3, 5, and 7. Day 7 Bone Marrow Consolidation (9 weeks) (Phase II) Prednisone Taper, cyclophosphamide, cytosine arabinoside (Ara-C), mercaptopurine, vincristine sulfate, pegaspargase, IT Methotrexate and radiation therapy.
|
Drug: asparaginase
Given IV
Other Names:
Drug: cyclophosphamide
Given IV
Other Names:
Drug: cytarabine
Given IV
Other Names:
Drug: daunorubicin hydrochloride
Given IV
Other Names:
Drug: dexamethasone
Given IV
Other Names:
Drug: doxorubicin hydrochloride
Given IV
Other Names:
Drug: idarubicin
Given IV
Other Names:
Drug: mercaptopurine
Given IV
Other Names:
Drug: methotrexate
Given PO
Other Name: NSC-740
Drug: pegaspargase
Given IV
Other Names:
Drug: prednisone
Given PO
Other Name: NSC-10023
Drug: thioguanine
Given IV
Other Names:
Drug: vincristine sulfate
Given IV
Other Names:
Radiation: radiation therapy
|
Show Detailed Description
Eligibility| Ages Eligible for Study: | 1 Year to 21 Years |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
Criteria
DISEASE CHARACTERISTICS: Acute lymphocytic leukemia (ALL) with M3 bone marrow No FAB L3 morphology CNS or overt testicular leukemia at diagnosis allowed High risk status 10-21 years old with any white blood count (WBC) 1-9 years old with WBC of 50,000/mm3 or greater
PATIENT CHARACTERISTICS: Age: 1 to 21 Performance status: Not specified Life expectancy: Not specified Hematopoietic: See Disease Characteristics Hepatic: Not specified Renal: Not specified
PRIOR CONCURRENT THERAPY: No prior therapy for ALL except: Emergency therapy for blast crisis, superior vena cava syndrome, or renal failure due to leukemic infiltration Biologic therapy: Not specified Chemotherapy: Intrathecal cytarabine or methotrexate allowed at diagnostic lumbar puncture Induction therapy must begin within 72 hours after intrathecal injection Endocrine therapy: At least 1-2 months since prior prednisone, for less than 48 hours, for reactive airway disease Inhalational steroids allowed Radiotherapy: Not specified Surgery: Not specified
Contacts and Locations
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To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.
For general information, see Learn About Clinical Studies.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00002812
Show 35 Study Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00002812
Show 35 Study Locations
Sponsors and Collaborators
Children's Oncology Group
Investigators
| Study Chair: | Nita L. Seibel, MD | Children's Research Institute |
More Information
Additional Information:
Publications:
Arce FJ, Seibel N, Gaynon PS, et al.: Pharmacokinetics and pharmacodynamics of asparaginases in antibody-negative pediatric patients with higher risk acute lymphoblastic leukemia (ALL): a report from CCG-1961. [Abstract] J Clin Oncol 24 (Suppl 18): A-9027, 508s, 2006.
Avramis VI, Ettinger L, Martin-Aragon S, et al.: Anti-asparaginase (ASNase) antibody (Ab) in pediatric patients in high risk ALL study (CCG-1961): correlation of Ab and clinical allergy. [Abstract] Proceedings of the American Society of Clinical Oncology 19: A2319, 2000.
Avramis VI, Panosyan E, Avramis IA, et al.: Anti-asparaginase (ASNase) antibody (Ab) and ASNase activity in children with higher risk acute lymphoblastic leukemia (HR ALL) (CCG-1961). [Abstract] Proceedings of the American Society of Clinical Oncology 21: A-1592, 2002.
Dhall G, Jones T, Radvinsky D, et al.: Adverse reactions to PEG and Erwinia asparaginase and correlation with anti-asparaginase antibody data and survival in children with acute lymphoblastic leukemia (ALL): A report from the Children's Oncology Group study CCG 1961. [Abstract] Blood 114 (22): A-3077, 2009.
Dhall G, Robison NJ, Rubin JI, et al.: Incidence of adverse reactions to post-induction asparaginase (ASP) therapy in children and adolescents with high-risk acute lymphoblastic leukemia (ALL): A report from the Children's Oncology Group Study CCG-1961. [Abstract] J Clin Oncol 26 (Suppl 15): A-10021, 2008.
Freyer DR, Seibel NL, La MK, et al.: Survival after relapse in higher risk acute lymphoblastic leukemia (ALL) in children and adolescents is independent of prior treatment intensity: a report from the Children's Oncology Group (COG). [Abstract] Blood 112 (11): A-917, 2008.
Hastings C, Sather HN, Seibel NL, et al.: Outcomes in children and adolescents with a markedly elevated white blood cell count (>200,000) at diagnosis of high risk acute lymphoblastic leukemia (ALL): a report from the Children's Oncology Group. [Abstract] Blood 108 (11): A-1870, 2006.
Hastings C, Whitlock JA, La M, et al.: Improved outcome of children with Down syndrome (DS) and high risk acute lymphocytic leukemia (HR-ALL): a report of CCG-1961. [Abstract] Blood 110 (11): A-586, 2007.
Nachman J, Siebel N, Sather H, et al.: Outcome for adolescent and young adults 16-21 years of age (AYA) with acute lymphoblastic leukemia (ALL) treated on the Children' s Cancer Group (CCG) 1961 study. [Abstract] Blood 104 (11): A-683, 2004.
Panosyan EH, Seibel NL, Grigoryan RS, et al.: Pharmacokinetics and pharmacodynamics of three asparaginases in pediatric patients with higher risk acute lymphoblastic leukemia: a report from CCG-1961. [Abstract] Blood 104 (11): A-2745, 2004.
Seibel NL, Asselin BL, Nachman JB, et al.: Treatment of high risk T-cell acute lymphoblastic leukemia (T-ALL): comparison of recent experience of the Children's Cancer Group (CCG) and Pediatric Oncology Group (POG). [Abstract] Blood 104 (11): A-681, 2004.
| Responsible Party: | Children's Oncology Group |
| ClinicalTrials.gov Identifier: | NCT00002812 History of Changes |
| Other Study ID Numbers: | 1961, CCG-1961, CDR0000064953 |
| Study First Received: | November 1, 1999 |
| Last Updated: | August 23, 2013 |
| Health Authority: | United States: Federal Government |
Keywords provided by Children's Oncology Group:
|
untreated childhood acute lymphoblastic leukemia L1 childhood acute lymphoblastic leukemia L2 childhood acute lymphoblastic leukemia |
Additional relevant MeSH terms:
|
Leukemia Leukemia, Lymphoid Precursor Cell Lymphoblastic Leukemia-Lymphoma Immune System Diseases Immunoproliferative Disorders Lymphatic Diseases Lymphoproliferative Disorders Neoplasms Neoplasms by Histologic Type 6-Mercaptopurine Asparaginase Cyclophosphamide Cytarabine Daunorubicin Doxorubicin |
Idarubicin Liposomal doxorubicin Methotrexate Pegaspargase Prednisone Vincristine Abortifacient Agents Abortifacient Agents, Nonsteroidal Alkylating Agents Anti-Infective Agents Anti-Inflammatory Agents Antibiotics, Antineoplastic Antimetabolites Antimetabolites, Antineoplastic Antimitotic Agents |
ClinicalTrials.gov processed this record on February 27, 2015