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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00002798
First received: November 24, 2000
Last updated: January 15, 2013
Last verified: January 2013
  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:

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
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):
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 April 23, 2014