Combination Chemotherapy in Treating Children With Newly Diagnosed Acute Myeloid Leukemia or Myelodysplastic Syndrome
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| ClinicalTrials.gov Identifier: NCT00002517 |
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Recruitment Status :
Completed
First Posted : January 27, 2003
Last Update Posted : June 22, 2010
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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 may kill more cancer cells. It is not yet known which regimen of combination chemotherapy is more effective for acute myeloid leukemia or myelodysplastic syndrome.
PURPOSE: Randomized phase III trial to compare the effectiveness of different combination chemotherapy regimens in treating children who have newly diagnosed acute myeloid leukemia or myelodysplastic syndrome.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Leukemia Myelodysplastic Syndromes | Drug: cytarabine Drug: daunorubicin hydrochloride Drug: dexamethasone Drug: etoposide Drug: idarubicin Drug: mitoxantrone hydrochloride Drug: thioguanine Procedure: allogeneic bone marrow transplantation Radiation: radiation therapy | Phase 3 |
OBJECTIVES:
- Compare the efficacy of idarubicin vs mitoxantrone in induction and first intensification in terms of achieving and maintaining complete remissions in children with acute myeloid leukemia or myelodysplastic syndrome.
OUTLINE: This is a randomized, multicenter study. Patients are stratified according to center and disease type (de novo acute myeloid leukemia (AML) vs AML secondary to myelodysplastic syndrome (MDS) vs MDS).
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Induction: Patients are randomized to 1 of 2 treatment arms.
- Arm I: Patients receive cytarabine (ARA-C) IV continuously on days 1 and 2 and then IV over 30 minutes every 12 hours on days 3-8, mitoxantrone IV on days 3-5, etoposide (VP-16) IV over 1 hour on days 6-8, and ARA-C intrathecally (IT) on days 1 and 8.
- Arm II: Patients receive ARA-C and VP-16 as in arm I and idarubicin IV on days 3-5.
Patients on both arms with CNS disease at presentation receive ARA-C IT every 3 days until the CSF clears and then weekly until the first intensification. After induction, patients on both arms proceed to first intensification, regardless of response.
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First intensification: When blood counts recover and within 40 days after initiating induction, patients are randomized to 1 of 2 treatment arms.
- Arm III: Patients receive high-dose ARA-C IV over 3 hours every 12 hours on days 1-3 (if allogeneic bone marrow transplantation (BMT) is planned) or days 1-4 (if allogeneic BMT is not planned) and mitoxantrone IV on days 7-9.
- Arm IV: Patients receive high-dose ARA-C as in arm III and idarubicin IV on days 7-9.
- Patients who achieve complete remission (CR) after first intensification and have an HLA-identical, chronic myelomonocytic leukemia-nonreactive, sibling donor undergo allogeneic BMT. Patients who achieve CR after intensification and have no suitable donor receive intensive chemotherapy as defined below. All patients with chloroma at presentation undergo local radiotherapy beginning after final intensification.
- Second intensification: When blood counts recover, patients receive daunorubicin IV continuously, ARA-C IV continuously, VP-16 IV continuously, oral thioguanine, and oral dexamethasone on days 1-4 and 11-14 and ARA-C IT on days 1, 4, 11, and 14.
- Third intensification: When blood counts recover, patients receive high-dose ARA-C IV over 3 hours every 12 hours on days 1-3 and VP-16 IV over 1 hour on days 2-5. When blood counts recover, autologous bone marrow is harvested in the event of subsequent relapse.
- Maintenance: When blood counts recover, patients receive oral thioguanine daily and ARA-C subcutaneously 4 days a month for 1 year.
PROJECTED ACCRUAL: A total of 310 patients will be accrued for this study within 5 years.
| Study Type : | Interventional (Clinical Trial) |
| Allocation: | Randomized |
| Primary Purpose: | Treatment |
| Official Title: | IDA VS MTZ IN INDUCTION AND INTENSIFICATION TREATMENT OF AML OR MDS IN CHILDREN, A PHASE III RANDOMIZED STUDY |
| Study Start Date : | March 1993 |
| Actual Primary Completion Date : | May 2010 |
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| Ages Eligible for Study: | up to 14 Years (Child) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
DISEASE CHARACTERISTICS:
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Newly diagnosed acute myeloid leukemia (AML) based on the cytological, cytochemical, and immunological criteria of the FAB classification
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Must meet 1 of the following criteria:
- More than 30% blasts in marrow (calculation based on the total number of nucleated cells except lymphocytes and plasmocytes)
- Presence of granulocytic sarcoma (chloroma)
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Disease must be associated with at least 1 of the following:
- More than 3% myeloperoxidase- or Sudan black-positive blasts
- More than 3% platelet peroxidase-positive blasts
- More than 20% esterase-positive blasts
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Immunological markers compatible with a myeloid differentiation, including 1 of the following criteria:
- Blasts positive for myeloid-associated antigen and negative for B- or T-lymphocyte antigens
- Blasts positive for at least 2 myeloid antigens (except CD3 and CD8)
- A cytogenetic abnormality associated with AML OR
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Newly diagnosed myelodysplastic syndrome (MDS) based on the cytological and cytochemical criteria of the FAB classification
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Eligible subtypes:
- Refractory anemia with excess blasts (RAEB)
- RAEB in transformation
- Chronic myelomonocytic leukemia
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- No promyelocytic leukemia (M3 or M3v) treated with tretinoin (protocol EORTC-06915)
- No AML secondary to hematologic or malignant disease other than MDS
- Registration must occur within 48 hours of diagnosis
PATIENT CHARACTERISTICS:
Age:
- Under 15
Performance status:
- Not specified
Life expectancy:
- Not specified
Hematopoietic:
- See Disease Characteristics
- No uncontrolled bleeding disorder
Hepatic:
- Not specified
Renal:
- No renal failure
Cardiovascular:
- No congenital heart disease
Other:
- No encephalopathy
- No genetic disorders
- No uncontrolled infection
PRIOR CONCURRENT THERAPY:
Biologic therapy:
- Not specified
Chemotherapy:
- Not specified
Endocrine therapy:
- Not specified
Radiotherapy:
- Not specified
Surgery:
- Not specified
Other:
- No prior antileukemic therapy
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): NCT00002517
Show 23 study locations
| Study Chair: | Catherine Behar, MD | Hopital Americain |
| ClinicalTrials.gov Identifier: | NCT00002517 |
| Other Study ID Numbers: |
CDR0000078212 EORTC-58921 |
| First Posted: | January 27, 2003 Key Record Dates |
| Last Update Posted: | June 22, 2010 |
| Last Verified: | December 2002 |
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childhood myelodysplastic syndromes 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 with excess blasts refractory anemia with excess blasts in transformation chronic myelomonocytic leukemia de novo myelodysplastic syndromes childhood acute minimally differentiated myeloid leukemia (M0) |
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Leukemia Preleukemia Myelodysplastic Syndromes Syndrome Disease Pathologic Processes Neoplasms by Histologic Type Neoplasms Bone Marrow Diseases Hematologic Diseases Precancerous Conditions Cytarabine Dexamethasone Etoposide Daunorubicin |
Mitoxantrone Idarubicin Thioguanine Anti-Inflammatory Agents Antiemetics Autonomic Agents Peripheral Nervous System Agents Physiological Effects of Drugs Gastrointestinal Agents Glucocorticoids Hormones Hormones, Hormone Substitutes, and Hormone Antagonists Antineoplastic Agents, Hormonal Antineoplastic Agents Antineoplastic Agents, Phytogenic |