Combination Chemotherapy With or Without Bone Marrow Transplantation in Treating Children With Acute Myelogenous Leukemia or Myelodysplastic Syndrome - Full Text View

Sponsor:	Children's Oncology Group
Collaborator:	National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00002798

Purpose

RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Combining chemotherapy with bone marrow transplantation may allow the doctor to give higher doses of chemotherapy drugs and kill more cancer cells. It is not yet known which treatment regimen is more effective for acute myelogenous leukemia or myelodysplastic syndrome.

PURPOSE: Randomized phase III trial to compare the effectiveness of different chemotherapy regimens with or without bone marrow transplantation in treating children who have acute myelogenous leukemia or myelodysplastic syndrome.

Condition	Intervention	Phase
Leukemia Myelodysplastic Syndromes	Biological: aldesleukin Biological: filgrastim Drug: asparaginase Drug: busulfan Drug: cyclophosphamide Drug: cytarabine Drug: daunorubicin hydrochloride Drug: dexamethasone Drug: etoposide Drug: fludarabine phosphate Drug: idarubicin Drug: methotrexate Drug: therapeutic hydrocortisone Drug: thioguanine Procedure: allogeneic bone marrow transplantation Radiation: radiation therapy	Phase III

Study Type:	Interventional
Study Design:	Allocation: Randomized Primary Purpose: Treatment
Official Title:	A PHASE III STUDY IN CHILDREN WITH UNTREATED ACUTE MYELOGENOUS LEUKEMIA (AML) OR MYELODYSPLASTIC SYNDROME (MDS)

Resource links provided by NLM:

MedlinePlus related topics: Acute Myeloid Leukemia Anemia Bone Marrow Transplantation Cancer Leukemia Myelodysplastic Syndromes

Drug Information available for: Dexamethasone Hydrocortisone acetate Cyclophosphamide Hydrocortisone Busulfan Methotrexate Cytarabine hydrochloride Daunorubicin Fludarabine Daunorubicin hydrochloride Etoposide Dexamethasone acetate Idarubicin hydrochloride Idarubicin Fludarabine monophosphate Doxiproct plus Proctofoam-HC Hydrocortisone hemisuccinate Hydrocortamate Aldesleukin Etoposide phosphate Filgrastim Lenograstim Granulocyte colony-stimulating factor Hydrocortisone 21-sodium succinate Cytarabine Thioguanine Hydrocortisone cypionate Dexamethasone Sodium Phosphate Cortisol succinate Cortisol 21-phosphate L-Asparaginase

U.S. FDA Resources

Further study details as provided by National Cancer Institute (NCI):

Estimated Enrollment:	880
Study Start Date:	August 1996

Show Detailed Description

Eligibility

Ages Eligible for Study:	up to 21 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

DISEASE CHARACTERISTICS:

Histologically confirmed previously untreated acute myeloid leukemia (AML) in patients 1 month to 21 years of age
- Infants under 1 month with progressive disease eligible
  - Supportive care may be given to confirm that the leukemia is not regressing prior to entry
- No acute promyelocytic leukemia (FAB M3)
- No acute undifferentiated leukemia (FAB M0)
Histochemical verification of AML required by the following stains:
- Wright or Giemsa
- Peroxidase
- PAS
- Chloroacetate esterase
- Sudan black
- Nonspecific esterase (NSE) with and without fluoride (NaF) inhibition
- Combined NSE/NaF and butyrate inhibition or diagnosis of megakaryoblastic leukemia (FAB M7) should be supported by one of the following:
  - CD41 reactivity
  - Glycoprotein 1b reactivity
  - Factor VIII-related antigen reactivity
  - Platelet peroxidase on electron microscopy
The following are also eligible:
- Myelodysplastic syndromes, including:
  - Refractory anemia (RA) *
  - RA with ringed sideroblasts (RARS) *
  - RA with excess blasts (RAEB)
  - RAEB in transformation (RAEBt)
  - Chronic myelomonocytic leukemia (CMML)
- AML with monosomy 7
- Granulocytic sarcoma (chloroma) with or without marrow involvement
- Mixed lineage leukemia with 2 morphologically defined populations provided the predominant population is myeloid
No Downs syndrome
No juvenile chronic myelogenous leukemia
No Fanconi's anemia
No secondary AML NOTE: * RA and RARS may be registered and observed until treatment deemed necessary

PATIENT CHARACTERISTICS:

Age:

Under 22

Performance status:

Not specified

Life expectancy:

Not specified

Hematopoeitic:

Not specified

Hepatic:

Not specified

Renal:

Not specified

PRIOR CONCURRENT THERAPY:

Biologic therapy:

Not specified

Chemotherapy:

No prior anticancer chemotherapy

Endocrine therapy:

Prior topical or inhaled steroids for nonmalignant conditions allowed

Radiotherapy :

No prior anticancer radiotherapy

Surgery:

Not specified

Other:

No prior antileukemic therapy

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00002798

Show 231 Study Locations

Sponsors and Collaborators

Children's Oncology Group

National Cancer Institute (NCI)

Investigators

Study Chair:

Beverly J. Lange, MD

Children's Hospital of Philadelphia

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

Publications:

Lange BJ, Yang RK, Gan J, Hank JA, Sievers EL, Alonzo TA, Gerbing RB, Sondel PM. Soluble interleukin-2 receptor ? activation in a Children's Oncology Group randomized trial of interleukin-2 Therapy for Pediatric Acute Myeloid Leukemia. Pediatr Blood Cancer. 2011 Jun 16; [Epub ahead of print]

Lange BJ, Smith FO, Feusner J, Barnard D, Dinndorf P, Feig S, Heerema NA, Arndt C, Arceci RJ, Seibel N, Weiman M, Dusenbery K, Shannon K, Luna-Fineman S, Gerbing RB, Alonzo TA. Outcomes in CCG-2961, a Children's Oncology Group phase 3 trial for untreated pediatric acute myeloid leukemia (AML): a report from the Children's Oncology Group. Blood. 2007 Nov 13; [Epub ahead of print]

Lange BJ, Gerbing RB, Feusner J, Skolnik J, Sacks N, Smith FO, Alonzo TA. Mortality in overweight and underweight children with acute myeloid leukemia. JAMA. 2005 Jan 12;293(2):203-11.

Lange BJ, Smith FO, Dinndorf PA, et al.: Outcomes in CCG-2961, a Children's Cancer Group Phase III trial for untreated acute myeloid leukemia (AML). [Abstract] Blood 106 (11): A-169, 2005.

Ho PA, Kuhn J, Gerbing RB, Pollard JA, Zeng R, Miller KL, Heerema NA, Raimondi SC, Hirsch BA, Franklin JL, Lange B, Gamis AS, Alonzo TA, Meshinchi S. WT1 Synonymous SNP rs16754 Correlates With Higher mRNA Expression and Predicts Significantly Improved Outcome in Favorable-Risk Pediatric Acute Myeloid Leukemia: A Report From the Children's Oncology Group. J Clin Oncol. 2010 Dec 28; [Epub ahead of print]

Johnston DL, Alonzo TA, Gerbing RB, Lange BJ, Woods WG. Superior outcome of pediatric acute myeloid leukemia patients with orbital and CNS myeloid sarcoma: A report from the Children's Oncology Group. Pediatr Blood Cancer. 2011 May 25; [Epub ahead of print]

Ho PA, Zeng R, Alonzo TA, Gerbing RB, Miller KL, Pollard JA, Stirewalt DL, Heerema NA, Raimondi SC, Hirsch B, Franklin JL, Lange B, Meshinchi S. Prevalence and prognostic implications of WT1 mutations in pediatric acute myeloid leukemia (AML): a report from the Children's Oncology Group. Blood. 2010 Apr 22; [Epub ahead of print]

Johnston DL, Alonzo TA, Gerbing RB, Lange BJ, Woods WG. The presence of central nervous system disease at diagnosis in pediatric acute myeloid leukemia does not affect survival: A Children's Oncology Group study. Pediatr Blood Cancer. 2010 Sep;55(3):414-20.

Phillips CL, Gerbing R, Alonzo T, Perentesis JP, Harley IT, Meshinchi S, Bhatla D, Radloff G, Davies SM. MDM2 polymorphism increases susceptibility to childhood acute myeloid leukemia: A report from the Children's Oncology Group. Pediatr Blood Cancer. 2010 Aug;55(2):248-53.

Pollard JA, Alonzo TA, Gerbing RB, Ho PA, Zeng R, Ravindranath Y, Dahl G, Lacayo NJ, Becton D, Chang M, Weinstein HJ, Hirsch B, Raimondi SC, Heerema NA, Woods WG, Lange BJ, Hurwitz C, Arceci RJ, Radich JP, Bernstein ID, Heinrich MC, Meshinchi S. Prevalence and prognostic significance of KIT mutations in pediatric core binding factor AML patients enrolled on serial pediatric cooperative trials for de novo AML. Blood. 2010 Jan 7; [Epub ahead of print]

Berman JN, Gerbing RB, Sung L, et al.: Prevalence and clinical implications of N-RAS mutations in childhood AML - A report from the Children's Oncology Group. [Abstract] Blood 114 (22): A-3115, 2009.

Bhatla D, Gerbing RB, Alonzo TA, Conner H, Ross JA, Meshinchi S, Zhai X, Zamzow T, Mehta PA, Geiger H, Perentesis J, Davies SM. Cytidine deaminase genotype and toxicity of cytosine arabinoside therapy in children with acute myeloid leukemia. Br J Haematol. 2008 Nov 22; [Epub ahead of print]

Ho PA, Alonzo TA, Gerbing RB, Pollard J, Stirewalt DL, Hurwitz C, Heerema NA, Hirsch B, Raimondi SC, Lange B, Franklin JL, Radich JP, Meshinchi S. Prevalence and prognostic implications of CEBPA mutations in pediatric AML: a report from the Children's Oncology Group. Blood. 2009 Mar 20; [Epub ahead of print]

Kunty MA, Alonzo TA, Gerbing RB, et al.: RUNX1 mutations in pediatric AML: A report from the Children's Oncology Group. [Abstract] Blood 114 (22): A-2614, 2009.

Bhatla D, Gerbing RB, Alonzo TA, Mehta PA, Deal K, Elliott J, Meshinchi S, Geiger H, Perentesis JP, Lange BJ, Davies SM. DNA repair polymorphisms and outcome of chemotherapy for acute myelogenous leukemia: a report from the Children's Oncology Group. Leukemia. 2007 Nov 22; [Epub ahead of print]

Horan JT, Alonzo TA, Lyman GH, Gerbing RB, Lange BJ, Ravindranath Y, Becton D, Smith FO, Woods WG. Impact of Disease Risk on Efficacy of Matched Related Bone Marrow Transplantation for Pediatric Acute Myeloid Leukemia: The Children's Oncology Group. J Clin Oncol. 2008 Oct 27; [Epub ahead of print]

Mehta PA, Gerbing RB, Alonzo TA, Elliott JS, Zamzow TA, Combs M, Stover E, Ross JA, Perentesis JP, Meschinchi S, Lange BJ, Davies SM. FAS promoter polymorphism: outcome of childhood acute myeloid leukemia. A children's oncology group report. Clin Cancer Res. 2008 Dec 1;14(23):7896-9.

Meshinchi S, Stirewalt DL, Alonzo TA, Boggon TJ, Gerbing RB, Rocnik JL, Lange BJ, Gilliland DG, Radich JP. Structural and numerical variation of FLT3/ITD in pediatric AML. Blood. 2008 Feb 27; [Epub ahead of print]

Sung L, Alonzo TA, Gerbing RB, Aplenc R, Lange BJ, Woods WG, Feusner J, Franklin J, Patterson MJ, Gamis AS. Respiratory syncytial virus infections in children with acute myeloid leukemia: A report from the Children's Oncology Group. Pediatr Blood Cancer. 2008 Aug 4; [Epub ahead of print]

Barbaric D, Alonzo TA, Gerbing RB, Meshinchi S, Heerema NA, Barnard DR, Lange BJ, Woods WG, Arceci RJ, Smith FO. Minimally differentiated acute myeloid leukemia (FAB AML-M0) is associated with an adverse outcome in children: a report from the Children's Oncology Group studies CCG-2891 and -2961. Blood. 2006 Dec 7; [Epub ahead of print]

Pollard J, Alonzo T, Gerbing R, et al.: Prevalence and prognostic significance of c-KIT mutations in pediatric CBF AML patients enrolled on serial CCG/COG protocols. [Abstract] Blood 110 (11): A-1442, 2007.

Brown P, McIntyre E, Rau R, et al.: Incidence and clinical significance of nucleophosmin mutations in childhood AML: a Childrens Oncology Group study. [Abstract] Blood 108 (11): A-221, 2006.

Children's Oncology Group; Aplenc R, Alonzo TA, Gerbing RB, Smith FO, Meshinchi S, Ross JA, Perentesis J, Woods WG, Lange BJ, Davies SM. Ethnicity and survival in childhood acute myeloid leukemia: a report from the Children's Oncology Group. Blood. 2006 Jul 1;108(1):74-80. Epub 2006 Mar 14.

Loh ML, Reynolds MG, Vattikuti S, Gerbing RB, Alonzo TA, Carlson E, Cheng JW, Lee CM, Lange BJ, Meshinchi S; Children's Cancer Group. PTPN11 mutations in pediatric patients with acute myeloid leukemia: results from the Children's Cancer Group. Leukemia. 2004 Nov;18(11):1831-4.

Perentesis JP, Alonzo TA, Gerbing R, et al.: Polymorphism in folate metabolism and outcomes of therapy in children with AML with and without Down Syndrome. [Abstract] Blood 102 (11 Pt 1): A-479, 2003.

Sievers EL, Lange BJ, Alonzo TA, et al.: Immunophenotypic evidence of leukemia after induction therapy predicts relapse: results from a prospective Children's Cancer Group Study of 252 acute myeloid leukemia patients. [Abstract] 2003 Pediatric Academic Societies' Annual Meeting, May 3-6, Seattle, Washington. A-1528, 2003. Available online Last accessed August 30, 2005.

Sievers EL, Lange BJ, Alonzo TA, Gerbing RB, Bernstein ID, Smith FO, Arceci RJ, Woods WG, Loken MR. Immunophenotypic evidence of leukemia after induction therapy predicts relapse: results from a prospective Children's Cancer Group study of 252 patients with acute myeloid leukemia. Blood. 2003 May 1;101(9):3398-406. Epub 2002 Dec 27.

ClinicalTrials.gov Identifier:	NCT00002798 History of Changes
Other Study ID Numbers:	CDR0000064883, COG-2961, CCG-2961
Study First Received:	November 24, 2000
Last Updated:	July 8, 2011
Health Authority:	United States: Federal Government

Keywords provided by National Cancer Institute (NCI):

untreated childhood acute myeloid leukemia and other myeloid malignancies
childhood acute myeloblastic leukemia without maturation (M1)
childhood acute myeloblastic leukemia with maturation (M2)
childhood acute myelomonocytic leukemia (M4)
childhood acute monoblastic leukemia (M5a)
childhood acute monocytic leukemia (M5b)
childhood acute erythroleukemia (M6)
childhood acute megakaryocytic leukemia (M7)

refractory anemia
refractory anemia with ringed sideroblasts
refractory anemia with excess blasts
refractory anemia with excess blasts in transformation
chronic myelomonocytic leukemia
de novo myelodysplastic syndromes
secondary myelodysplastic syndromes
childhood myelodysplastic syndromes

Additional relevant MeSH terms:

Leukemia
Leukemia, Myeloid, Acute
Leukemia, Myeloid
Myelodysplastic Syndromes
Preleukemia
Neoplasms by Histologic Type
Neoplasms
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Fludarabine monophosphate
Fludarabine
Aldesleukin
Asparaginase
Busulfan

Cyclophosphamide
Cytarabine
Daunorubicin
Dexamethasone
Etoposide
Idarubicin
Methotrexate
Thioguanine
Lenograstim
Vidarabine
Dexamethasone acetate
Cortisol succinate
Hydrocortisone acetate
Hydrocortisone
Dexamethasone 21-phosphate

ClinicalTrials.gov processed this record on February 09, 2012