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Combination Chemotherapy in Treating Children With Acute Lymphocytic Leukemia

This study has been completed.
Sponsor:
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
  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:


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:
  • E. coli
  • Elspar
  • NSC-109229
Drug: cyclophosphamide
Given IV
Other Names:
  • Cytoxan
  • NSC-26271
Drug: cytarabine
Given IV
Other Names:
  • Cytosine Arabinoside
  • Ara-C
  • Cytosar-U
  • NSC-63878
Drug: daunorubicin hydrochloride
Given IV
Other Names:
  • Daunomycin Hydrochloride
  • Cerrubidine
  • NSC-82151
Drug: dexamethasone
Given IV
Other Names:
  • Decadron
  • NSC-34521
Drug: doxorubicin hydrochloride
Given IV
Other Names:
  • Adriamycin
  • NSC-123127
Drug: idarubicin
Given IV
Other Names:
  • Idarubicin Hydrochloride
  • Idamycin
  • NSC-256439
Drug: mercaptopurine
Given IV
Other Names:
  • 6-MP
  • Purinethol
  • NSC-755
Drug: methotrexate
Given PO
Other Name: NSC-740
Drug: pegaspargase
Given IV
Other Names:
  • Asparaginase
  • Oncaspar
Drug: prednisone
Given PO
Other Name: NSC-10023
Drug: thioguanine
Given IV
Other Names:
  • 6-TG
  • NSC-752
Drug: vincristine sulfate
Given IV
Other Names:
  • Oncovin
  • NSC-67574
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:
  • E. coli
  • Elspar
  • NSC-109229
Drug: cyclophosphamide
Given IV
Other Names:
  • Cytoxan
  • NSC-26271
Drug: cytarabine
Given IV
Other Names:
  • Cytosine Arabinoside
  • Ara-C
  • Cytosar-U
  • NSC-63878
Drug: daunorubicin hydrochloride
Given IV
Other Names:
  • Daunomycin Hydrochloride
  • Cerrubidine
  • NSC-82151
Drug: dexamethasone
Given IV
Other Names:
  • Decadron
  • NSC-34521
Drug: doxorubicin hydrochloride
Given IV
Other Names:
  • Adriamycin
  • NSC-123127
Drug: idarubicin
Given IV
Other Names:
  • Idarubicin Hydrochloride
  • Idamycin
  • NSC-256439
Drug: mercaptopurine
Given IV
Other Names:
  • 6-MP
  • Purinethol
  • NSC-755
Drug: methotrexate
Given PO
Other Name: NSC-740
Drug: pegaspargase
Given IV
Other Names:
  • Asparaginase
  • Oncaspar
Drug: prednisone
Given PO
Other Name: NSC-10023
Drug: thioguanine
Given IV
Other Names:
  • 6-TG
  • NSC-752
Drug: vincristine sulfate
Given IV
Other Names:
  • Oncovin
  • NSC-67574
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:
  • E. coli
  • Elspar
  • NSC-109229
Drug: cyclophosphamide
Given IV
Other Names:
  • Cytoxan
  • NSC-26271
Drug: cytarabine
Given IV
Other Names:
  • Cytosine Arabinoside
  • Ara-C
  • Cytosar-U
  • NSC-63878
Drug: daunorubicin hydrochloride
Given IV
Other Names:
  • Daunomycin Hydrochloride
  • Cerrubidine
  • NSC-82151
Drug: dexamethasone
Given IV
Other Names:
  • Decadron
  • NSC-34521
Drug: doxorubicin hydrochloride
Given IV
Other Names:
  • Adriamycin
  • NSC-123127
Drug: idarubicin
Given IV
Other Names:
  • Idarubicin Hydrochloride
  • Idamycin
  • NSC-256439
Drug: mercaptopurine
Given IV
Other Names:
  • 6-MP
  • Purinethol
  • NSC-755
Drug: methotrexate
Given PO
Other Name: NSC-740
Drug: pegaspargase
Given IV
Other Names:
  • Asparaginase
  • Oncaspar
Drug: prednisone
Given PO
Other Name: NSC-10023
Drug: thioguanine
Given IV
Other Names:
  • 6-TG
  • NSC-752
Drug: vincristine sulfate
Given IV
Other Names:
  • Oncovin
  • NSC-67574
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:
  • E. coli
  • Elspar
  • NSC-109229
Drug: cyclophosphamide
Given IV
Other Names:
  • Cytoxan
  • NSC-26271
Drug: cytarabine
Given IV
Other Names:
  • Cytosine Arabinoside
  • Ara-C
  • Cytosar-U
  • NSC-63878
Drug: daunorubicin hydrochloride
Given IV
Other Names:
  • Daunomycin Hydrochloride
  • Cerrubidine
  • NSC-82151
Drug: dexamethasone
Given IV
Other Names:
  • Decadron
  • NSC-34521
Drug: doxorubicin hydrochloride
Given IV
Other Names:
  • Adriamycin
  • NSC-123127
Drug: idarubicin
Given IV
Other Names:
  • Idarubicin Hydrochloride
  • Idamycin
  • NSC-256439
Drug: mercaptopurine
Given IV
Other Names:
  • 6-MP
  • Purinethol
  • NSC-755
Drug: methotrexate
Given PO
Other Name: NSC-740
Drug: pegaspargase
Given IV
Other Names:
  • Asparaginase
  • Oncaspar
Drug: prednisone
Given PO
Other Name: NSC-10023
Drug: thioguanine
Given IV
Other Names:
  • 6-TG
  • NSC-752
Drug: vincristine sulfate
Given IV
Other Names:
  • Oncovin
  • NSC-67574
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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. 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
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
Dexamethasone
Doxorubicin
Idarubicin
Liposomal doxorubicin
Methotrexate
Pegaspargase
Prednisone
Vincristine
Abortifacient Agents
Abortifacient Agents, Nonsteroidal
Alkylating Agents
Anti-Infective Agents
Anti-Inflammatory Agents
Antibiotics, Antineoplastic
Antiemetics
Antimetabolites

ClinicalTrials.gov processed this record on November 20, 2014