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

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ClinicalTrials.gov Identifier: NCT00002798

Recruitment Status : Completed

First Posted : January 27, 2003

Last Update Posted : January 16, 2013

Sponsor:

Information provided by (Responsible Party):

National Cancer Institute (NCI)

Study Description

Brief Summary:

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. 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

Condition or disease	Intervention/treatment	Phase
Childhood Acute Erythroleukemia (M6) Childhood Acute Megakaryocytic Leukemia (M7) Childhood Acute Monoblastic Leukemia (M5a) Childhood Acute Monocytic Leukemia (M5b) Childhood Acute Myeloblastic Leukemia With Maturation (M2) Childhood Acute Myeloblastic Leukemia Without Maturation (M1) Childhood Acute Myelomonocytic Leukemia (M4) Childhood Myelodysplastic Syndromes Chronic Myelomonocytic Leukemia de Novo Myelodysplastic Syndromes Refractory Anemia Refractory Anemia With Excess Blasts Refractory Anemia With Excess Blasts in Transformation Refractory Anemia With Ringed Sideroblasts Secondary Myelodysplastic Syndromes Untreated Childhood Acute Myeloid Leukemia and Other Myeloid Malignancies	Drug: asparaginase Drug: daunorubicin hydrochloride Drug: fludarabine phosphate Drug: therapeutic hydrocortisone Procedure: allogeneic bone marrow transplantation Radiation: 3-dimensional conformal radiation therapy Biological: filgrastim Drug: cytarabine Drug: idarubicin Drug: dexamethasone Drug: thioguanine Drug: etoposide Drug: methotrexate Drug: cyclophosphamide Biological: aldesleukin Drug: busulfan	Phase 3

Show Detailed Description

Study Design


Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	880 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	None (Open Label)
Primary Purpose:	Treatment
Official Title:	A PHASE III STUDY IN CHILDREN WITH UNTREATED ACUTE MYELOGENOUS LEUKEMIA (AML) OR MYELODYSPLASTIC SYNDROME (MDS)
Study Start Date :	August 1996
Actual Primary Completion Date :	September 2006

Resource links provided by the National Library of Medicine

Genetics Home Reference related topics: Core binding factor acute myeloid leukemia Cytogenetically normal acute myeloid leukemia Familial acute myeloid leukemia with mutated CEBPA

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

Genetic and Rare Diseases Information Center resources: Myeloid Leukemia Acute Myeloid Leukemia Acute Non Lymphoblastic Leukemia Myelodysplastic Syndromes Chronic Myelomonocytic Leukemia Juvenile Myelomonocytic Leukemia Acute Myeloblastic Leukemia With Maturation Acute Myeloblastic Leukemia Without Maturation Acute Erythroid Leukemia Acute Megakaryoblastic Leukemia Acute Myelomonocytic Leukemia Di Guglielmo's Syndrome Acute Monoblastic Leukemia Sideroblastic Anemia Pyridoxine-refractory Autosomal Recessive Myelodysplastic/myeloproliferative Disease Chronic Myeloproliferative Disorders

U.S. FDA Resources

Arms and Interventions

Arm	Intervention/treatment
Experimental: Arm I (combination chemotherapy) Patients receive treatment as in induction therapy, plus G-CSF SC beginning on day 16 and continuing until blood counts recover. If CSF is clear by day 10 of induction, patients receive cytarabine IT on days 0, 10, and 35. If CSF is not clear, patients receive triple intrathecal therapy (TIT; cytarabine, hydrocortisone, methotrexate) on days 0 and 10. See Detailed Description	Drug: daunorubicin hydrochloride Other Names: Cerubidin Cerubidine daunomycin hydrochloride daunorubicin RP-13057 Drug: therapeutic hydrocortisone Other Names: Aeroseb-HC Barseb HC Cetacort Cort-Dome Cortef Procedure: allogeneic bone marrow transplantation Other Names: bone marrow therapy, allogeneic bone marrow therapy, allogenic transplantation, allogeneic bone marrow transplantation, allogenic bone marrow Biological: filgrastim Given SC Other Names: G-CSF Neupogen Drug: cytarabine Given IV or IT Other Names: ARA-C arabinofuranosylcytosine arabinosylcytosine Cytosar-U cytosine arabinoside Drug: idarubicin Given IV Other Names: 4-demethoxydaunorubicin 4-DMDR DMDR IDA Drug: dexamethasone Given PO Other Names: Aeroseb-Dex Decaderm Decadron DM DXM Drug: thioguanine Given PO Other Name: 6-TG Drug: etoposide Given IV Other Names: EPEG VP-16 VP-16-213 Drug: methotrexate Given IT Other Names: amethopterin Folex methylaminopterin Mexate MTX
Experimental: Arm II (combination chemotherapy) Patients receive fludarabine IV over 24 hours on days 0 and 1, cytarabine IV over 72 hours on days 2-4, and idarubicin IV over 15 minutes on days 0-2. G-CSF begins on day 6 and continues until blood counts recover. Patients also receive TIT on days -1 and 7, if CSF is not clear on day 10 of induction. Patients on both arms are reassessed on day 35. Those patients with M1 marrow proceed to intensification; all others are removed from the study. Intensification: See Detailed Description	Drug: asparaginase Other Names: ASNase Colaspase Crasnitin Elspar L-ASP Drug: fludarabine phosphate Other Names: 2-F-ara-AMP Beneflur Fludara Drug: therapeutic hydrocortisone Other Names: Aeroseb-HC Barseb HC Cetacort Cort-Dome Cortef Procedure: allogeneic bone marrow transplantation Other Names: bone marrow therapy, allogeneic bone marrow therapy, allogenic transplantation, allogeneic bone marrow transplantation, allogenic bone marrow Biological: filgrastim Given SC Other Names: G-CSF Neupogen Drug: cytarabine Given IV or IT Other Names: ARA-C arabinofuranosylcytosine arabinosylcytosine Cytosar-U cytosine arabinoside Drug: idarubicin Given IV Other Names: 4-demethoxydaunorubicin 4-DMDR DMDR IDA Drug: thioguanine Given PO Other Name: 6-TG Drug: methotrexate Given IT Other Names: amethopterin Folex methylaminopterin Mexate MTX Drug: cyclophosphamide Given IV Other Names: CPM CTX Cytoxan Endoxan Endoxana Drug: busulfan Other Names: BSF BU Misulfan Mitosan Myeloleukon
Experimental: Arm III (combination chemotherapy, aldesleukin) Patients receive interleukin-2 IV continuously on days 1-4 and 9-18.	Drug: daunorubicin hydrochloride Other Names: Cerubidin Cerubidine daunomycin hydrochloride daunorubicin RP-13057 Biological: filgrastim Given SC Other Names: G-CSF Neupogen Drug: cytarabine Given IV or IT Other Names: ARA-C arabinofuranosylcytosine arabinosylcytosine Cytosar-U cytosine arabinoside Drug: idarubicin Given IV Other Names: 4-demethoxydaunorubicin 4-DMDR DMDR IDA Drug: dexamethasone Given PO Other Names: Aeroseb-Dex Decaderm Decadron DM DXM Drug: thioguanine Given PO Other Name: 6-TG Drug: etoposide Given IV Other Names: EPEG VP-16 VP-16-213 Biological: aldesleukin Other Names: IL-2 Proleukin recombinant human interleukin-2 recombinant interleukin-2
Active Comparator: Arm IV (combination chemotherapy) No further treatment	Drug: daunorubicin hydrochloride Other Names: Cerubidin Cerubidine daunomycin hydrochloride daunorubicin RP-13057 Biological: filgrastim Given SC Other Names: G-CSF Neupogen Drug: cytarabine Given IV or IT Other Names: ARA-C arabinofuranosylcytosine arabinosylcytosine Cytosar-U cytosine arabinoside Drug: idarubicin Given IV Other Names: 4-demethoxydaunorubicin 4-DMDR DMDR IDA Drug: dexamethasone Given PO Other Names: Aeroseb-Dex Decaderm Decadron DM DXM Drug: thioguanine Given PO Other Name: 6-TG Drug: etoposide Given IV Other Names: EPEG VP-16 VP-16-213
Experimental: Arm V (combination chemotherapy, radiotherapy) Patients undergo radiotherapy to the chloroma 5 days a week for 2 weeks.	Drug: daunorubicin hydrochloride Other Names: Cerubidin Cerubidine daunomycin hydrochloride daunorubicin RP-13057 Radiation: 3-dimensional conformal radiation therapy Other Names: 3D conformal radiation therapy 3D-CRT Biological: filgrastim Given SC Other Names: G-CSF Neupogen Drug: cytarabine Given IV or IT Other Names: ARA-C arabinofuranosylcytosine arabinosylcytosine Cytosar-U cytosine arabinoside Drug: idarubicin Given IV Other Names: 4-demethoxydaunorubicin 4-DMDR DMDR IDA Drug: dexamethasone Given PO Other Names: Aeroseb-Dex Decaderm Decadron DM DXM Drug: thioguanine Given PO Other Name: 6-TG Drug: etoposide Given IV Other Names: EPEG VP-16 VP-16-213

Outcome Measures

Primary Outcome Measures :

Proportions of patients achieving remission rate during induction therapy [ Time Frame: Up to 42 days ]
Proportion of patients dying or with residual disease during induction therapy [ Time Frame: Up to 42 days ]
Time to marrow recovery (induction phase) [ Time Frame: Up to 42 days ]
Frequency of toxicities, including infectious complications (induction phase) [ Time Frame: Up to 42 days ]
Marrow status [ Time Frame: At 14 days ]
Percent of blasts [ Time Frame: At the end of induction therapy ]
Complete remission at the end of consolidation therapy [ Time Frame: Up to 5 years ]
Survival following consolidation [ Time Frame: Up to 5 years ]
Event-free survival following consolidation [ Time Frame: Up to 5 years ]
Overall survival (intensification) [ Time Frame: Up to 5 years ]
EFS (intensification) [ Time Frame: Up to 5 years ]

Eligibility Criteria

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Ages Eligible for Study:	up to 21 Years (Child, Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

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 megakaryoblasticleukemia (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
Performance status - Not specified
No prior anticancer chemotherapy
Prior topical or inhaled steroids for nonmalignant conditions allowed
No prior anticancer radiotherapy
No prior antileukemic therapy

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): NCT00002798

Locations


United States, California
Children's Oncology Group
Arcadia, California, United States, 91006-3776

Sponsors and Collaborators

National Cancer Institute (NCI)

Investigators


Principal Investigator:	Beverly Lange	Children's Oncology Group

More Information

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

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 Aug 5;116(5):702-10. doi: 10.1182/blood-2010-02-268953. Epub 2010 Apr 22.

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 patients with core binding factor AML enrolled on serial pediatric cooperative trials for de novo AML. Blood. 2010 Mar 25;115(12):2372-9. doi: 10.1182/blood-2009-09-241075. Epub 2010 Jan 7.

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 acute myeloid leukemia (AML): a report from the Children's Oncology Group. Blood. 2009 Jun 25;113(26):6558-66. doi: 10.1182/blood-2008-10-184747. Epub 2009 Mar 20.


Responsible Party:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00002798 History of Changes
Other Study ID Numbers:	NCI-2012-01834 2961 U10CA098543 ( U.S. NIH Grant/Contract ) CDR0000064883 ( Registry Identifier: PDQ (Physician Data Query) )
First Posted:	January 27, 2003 Key Record Dates
Last Update Posted:	January 16, 2013
Last Verified:	January 2013

Additional relevant MeSH terms:


Syndrome Leukemia Leukemia, Myeloid, Acute Anemia Myelodysplastic Syndromes Preleukemia Leukemia, Myeloid Leukemia, Myelomonocytic, Acute Leukemia, Myelomonocytic, Chronic Leukemia, Myelomonocytic, Juvenile Anemia, Refractory Anemia, Refractory, with Excess of Blasts Leukemia, Monocytic, Acute Leukemia, Erythroblastic, Acute Anemia, Aplastic	Leukemia, Megakaryoblastic, Acute Disease Pathologic Processes Neoplasms by Histologic Type Neoplasms Hematologic Diseases Bone Marrow Diseases Precancerous Conditions Myelodysplastic-Myeloproliferative Diseases Myeloproliferative Disorders Hydrocortisone 17-butyrate 21-propionate Hydrocortisone acetate Cortisol succinate Dexamethasone Hydrocortisone

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