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

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. 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	Intervention	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

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label 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:

Genetics Home Reference related topics: familial acute myeloid leukemia with mutated CEBPA

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 Hydrocortisone sodium succinate Cytarabine Thioguanine Hydrocortisone cypionate Dexamethasone acetate Dexamethasone sodium phosphate Asparaginase Hydrocortisone butyrate Methotrexate sodium Daunorubicin Fludarabine Daunorubicin hydrochloride Etoposide Hydrocortisone valerate Idarubicin hydrochloride Idarubicin Hydrocortisone probutate Fludarabine phosphate Aldesleukin Etoposide phosphate Filgrastim Lenograstim Granulocyte colony-stimulating factor Daunorubicin citrate

U.S. FDA Resources

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

Primary Outcome Measures:

Proportions of patients achieving remission rate during induction therapy [ Time Frame: Up to 42 days ] [ Designated as safety issue: No ]
Proportion of patients dying or with residual disease during induction therapy [ Time Frame: Up to 42 days ] [ Designated as safety issue: No ]
Time to marrow recovery (induction phase) [ Time Frame: Up to 42 days ] [ Designated as safety issue: No ]
Frequency of toxicities, including infectious complications (induction phase) [ Time Frame: Up to 42 days ] [ Designated as safety issue: Yes ]
Marrow status [ Time Frame: At 14 days ] [ Designated as safety issue: No ]
Percent of blasts [ Time Frame: At the end of induction therapy ] [ Designated as safety issue: No ]
Complete remission at the end of consolidation therapy [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
Survival following consolidation [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
Event-free survival following consolidation [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
Overall survival (intensification) [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
EFS (intensification) [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]

Enrollment:	880
Study Start Date:	August 1996
Primary Completion Date:	September 2006 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
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

Show Detailed Description

Eligibility

Ages Eligible for Study:	up to 21 Years
Genders Eligible for Study:	Both
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

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

No publications provided by National Cancer Institute (NCI)

Additional 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 Apr 22; [Epub ahead of print]

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]

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]

Responsible Party:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00002798 History of Changes
Other Study ID Numbers:	NCI-2012-01834, 2961, U10CA098543, CDR0000064883
Study First Received:	November 24, 2000
Last Updated:	January 15, 2013
Health Authority:	United States: Food and Drug Administration

Additional relevant MeSH terms:

Anemia
Anemia, Refractory
Anemia, Refractory, with Excess of Blasts
Neoplasms
Leukemia
Leukemia, Erythroblastic, Acute
Leukemia, Megakaryoblastic, Acute
Leukemia, Monocytic, Acute
Leukemia, Myeloid, Acute
Leukemia, Myeloid
Leukemia, Myelomonocytic, Acute
Leukemia, Myelomonocytic, Chronic
Myelodysplastic Syndromes
Preleukemia
Anemia, Aplastic

Hematologic Diseases
Bone Marrow Diseases
Neoplasms by Histologic Type
Myeloproliferative Disorders
Myelodysplastic-Myeloproliferative Diseases
Precancerous Conditions
Fludarabine
Fludarabine monophosphate
Aldesleukin
Asparaginase
Busulfan
Cyclophosphamide
Cytarabine
Daunorubicin
Dexamethasone

ClinicalTrials.gov processed this record on June 17, 2013