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NCT00003593 · CITED IN SOURCE DOCUMENTS

Chemotherapy in Treating Children With Down Syndrome and Myeloproliferative Disorder, Acute Myelogenous Leukemia, or Myelodysplastic Syndrome

An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.

Phase
PHASE3
Status at capture
COMPLETED
Registry last update
2013-06-27

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells. PURPOSE: Phase III trial to study the effectiveness of combination chemotherapy in treating children who have Down syndrome and myeloproliferative disorder, acute myelogenous leukemia, or myelodysplastic syndrome.

Open the original ClinicalTrials.gov record → · Download preserved record

What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

No posted result sections were captured. Registered plans do not establish that a treatment works.

Who could take part
eligibility Criteria
DISEASE CHARACTERISTICS: * Cytogenetically proven Down Syndrome (constitutional trisomy 21) with transient myeloproliferative disorder (TMD), myelodysplastic syndromes (MDS), or acute myelogenous leukemia (AML) * Must be confirmed by bone marrow aspirate, cerebrospinal fluid exam, or blood test * Trisomy 21 mosaicism allowed * Group I: * Diagnosis of TMD in patients no older than 90 days at initial presentation * Must have nonerythroid blasts (any amount) in the peripheral blood and one of the following: * Verification with a second sample * More than 5% bone marrow blasts * Hepatomegaly and/or splenomegaly * Lymphadenopathy * Cardiac or pleural effusions OR * Histologically or cytologically proven TMD with blasts in an affected organ or in fluid (pericardial, pleural, or peritoneal) * Bone marrow aspirate is required * Group II (closed to accrual as of 6/24/04): * Diagnosis of MDS or AML (except M3 subtype) in patients older than 90 days with more than 29% blasts in bone marrow (with or without history of TMD), or any of the following histologies: * Refractory anemia (RA) * RA with excess blasts (RAEB) * RAEB in transformation * RA with ringed sideroblasts (RARS) * Primary cytopenia (later confirmed by bone marrow aspirate as due to marrow hypoplasia) defined by one or more of the following: * Absolute neutrophil count less than 500/mm\^3 * Untransfused platelet count less than 30,000/mm\^3 * Untransfused hemoglobin less than 8 g/dL * The following diagnoses will be observed only: * RA with mild cytopenias\* * RARS with mild cytopenias\* * Mild primary cytopenias (one or more) without dysplasia (confirmed by hypoplastic bone marrow exam) NOTE: \* Platelet count 30-150,000/mm3, absolute neutrophil count 500-1,499/mm3, and hemoglobin greater than 8 g/dL * Granulocytic sarcoma (chloroma), with or without bone marrow involvement, allowed PATIENT CHARACTERISTICS: Age: * See Disease Characteristics * 21 and under Performance status: * Not specified Life expectancy: * Not specified Hematopoietic: * See Disease Characteristics Hepatic: * See Disease Characteristics Renal: * Not specified Cardiovascular: * Shortening fraction greater than 27% by echocardiogram\* OR * Ejection fraction greater than 47% by radionuclide angiogram\* NOTE: \*For patients with MDS and AML (as of 2/24/04, previously diagnosed MDS or AML closed to accrual; MDS or AML that develops (secondary to TMD) after study enrollment or MDS that requires initial observation \[with or without subsequent treatment\] allowed) PRIOR CONCURRENT THERAPY: Biologic therapy: * Not specified Chemotherapy: * Prior chemotherapy for TMD allowed * No prior chemotherapy for malignancy Endocrine therapy: * Concurrent topical or inhaled steroids for other conditions allowed Radiotherapy: * No prior radiotherapy for malignancy Surgery: * Not specified Other: * No prior antileukemic therapy * Prior enrollment on this study for TMD allowed
healthy Volunteers
false
maximum Age
21 Years
sex
ALL
std Ages
  1. CHILD
  2. ADULT
Treatment arms and interventions
arm Groups
  1. description
    Patients are observed if their transient myeloproliferative disorder (TMD) does not require intervention. Patients who require therapy for TMD undergo leukapheresis or exchange transfusion for up to 3 consecutive days. If the TMD does not resolve or there is significant organ involvement, patients receive low-dose cytarabine IV continuously on days 0-4. Treatment repeats at least every 2 weeks for up to 4 courses. Patients who experience a recurrence of TMD at least 8 weeks after resolution or have refractory disease may proceed to group II for further treatment. patients will continue to be followed for remission induction, EFS, DFS and OS regardless of the type of leukemia that develops.
    intervention Names
    1. Drug: cytarabine
    label
    Arm A: TMD patients only
    type
    EXPERIMENTAL
  2. description
    (closed to accrual as of 6/24/04 except for patients first enrolled in group I): Patients receive induction therapy comprising cytarabine IV continuously, daunorubicin hydrochloride IV continuously, and oral thioguanine twice daily on days 0-3. Treatment repeats every 28 days for 4 courses. Patients with no CNS disease at diagnosis receive cytarabine intrathecally (IT) on day 0. Patients with CNS disease at diagnosis receive cytarabine IT on days 0, 5, and 7. If CNS disease persists on day 7, patients receive up to 6 courses of cytarabine IT, therapeutic hydrocortisone IT, and methotrexate IT, twice weekly beginning on day 10. Asparaginase during Intensification 1 day 1 hour 18.
    intervention Names
    1. Drug: asparaginase
    2. Drug: cytarabine
    3. Drug: daunorubicin hydrochloride
    4. Drug: methotrexate
    5. Drug: therapeutic hydrocortisone
    6. Drug: thioguanine
    label
    Arm B: AML/MDS patients only
    type
    EXPERIMENTAL
interventions
  1. arm Group Labels
    1. Arm B: AML/MDS patients only
    description
    Given IV
    name
    asparaginase
    other Names
    1. Elspar
    2. Kidrolase
    3. Crasnitin
    4. Leunase
    5. NSC #109229
    type
    DRUG
  2. arm Group Labels
    1. Arm A: TMD patients only
    2. Arm B: AML/MDS patients only
    description
    Given IT
    name
    cytarabine
    other Names
    1. cytosine arabinoside
    2. AraC
    3. Cytosar
    4. NSC #063878
    type
    DRUG
  3. arm Group Labels
    1. Arm B: AML/MDS patients only
    description
    Given IV
    name
    daunorubicin hydrochloride
    other Names
    1. daunomycin
    2. DNR
    3. Cerubidine
    4. NSC #82151
    type
    DRUG
  4. arm Group Labels
    1. Arm B: AML/MDS patients only
    description
    Given IV
    name
    methotrexate
    other Names
    1. MTX
    2. amethopterin
    3. NSC #000740
    type
    DRUG
  5. arm Group Labels
    1. Arm B: AML/MDS patients only
    description
    Given IT
    name
    therapeutic hydrocortisone
    other Names
    1. Cortef
    2. Solu-cortef
    3. NSC #010483
    type
    DRUG
  6. arm Group Labels
    1. Arm B: AML/MDS patients only
    description
    Given IV
    name
    thioguanine
    other Names
    1. 6-thioguanine
    2. 6-TG
    3. NSC # 000752
    type
    DRUG
Study design
allocation
NON_RANDOMIZED
intervention Model
SINGLE_GROUP
masking Info
masking
NONE
primary Purpose
TREATMENT
Enrollment
count
254
type
ACTUAL
Registered outcome plans (not posted results)
primary Outcomes
  1. measure
    Event Free Survival
    time Frame
    Length of study
Full study description
brief Summary
RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells. PURPOSE: Phase III trial to study the effectiveness of combination chemotherapy in treating children who have Down syndrome and myeloproliferative disorder, acute myelogenous leukemia, or myelodysplastic syndrome.
detailed Description
OBJECTIVES: * Evaluate the efficacy of reduced-dose induction and intensification chemotherapy, in terms of remission rate, disease-free survival rate, and acute morbidity and mortality, in children with Down syndrome and acute myelogenous leukemia or myelodysplastic syndromes. * Define the understanding of the natural history of transient myeloproliferative disorder (TMD) in children with Down syndrome. * Determine whether there is a reduction of sequelae in long-term survivors after treatment with this regimen. * Determine the incidence of subsequent leukemia in patients with transient myeloproliferative disorder treated with this regimen. * Determine the predictive risk factors for developing subsequent leukemia in patients with transient myeloproliferative disorder treated with this regimen. OUTLINE: This is a multicenter study. * Group I: Patients are observed if their transient myeloproliferative disorder (TMD) does not require intervention. Patients who require therapy for TMD undergo leukapheresis or exchange transfusion for up to 3 consecutive days. If the TMD does not resolve or there is significant organ involvement, patients receive low-dose cytarabine IV continuously on days 0-4. Treatment repeats at least every 2 weeks for up to 4 courses. Patients who experience a recurrence of TMD at least 8 weeks after resolution or have refractory disease may proceed to group II for further treatment. * Group II (closed to accrual as of 6/24/04 except for patients first enrolled in group I): Patients receive induction therapy comprising cytarabine IV continuously, daunorubicin IV continuously, and oral thioguanine twice daily on days 0-3. Treatment repeats every 28 days for 4 courses. Patients with no CNS disease at diagnosis receive cytarabine intrathecally (IT) on day 0. Patients with CNS disease at diagnosis receive cytarabine IT on days 0, 5, and 7. If CNS disease persists on day 7, patients receive up to 6 courses of cytarabine IT, hydrocortisone IT, and methotrexate IT, twice weekly beginning on day 10. Patients who achieve remission after induction therapy receive 2 courses of intensification therapy, for approximately 4 months. During the first course, patients receive cytarabine IV over 3 hours twice daily on days 0, 1, 7, and 8. Patients also receive asparaginase intramuscularly on days 1 and 8. The second course of therapy comprises CNS prophylaxis. Patients with no CNS disease at diagnosis or whose CNS disease resolved by day 7 of induction therapy receive cytarabine IT on days 0, 7, and 14. Patients with persistent CNS disease on day 7 of induction therapy receive cytarabine IT, hydrocortisone IT, and methotrexate IT on days 0, 7, and 14. Patients are followed monthly for 18 months, every 3 months for 1 year, every 6 months for 2.5 years, and then annually thereafter. PROJECTED ACCRUAL: A total of 70 patients with acute myeloid leukemia or myelodysplastic syndromes will be accrued for this study within 3.2 years. A total of 88 patients with transient myeloproliferative disorder who enter remission will be accrued for this study within 5 years.
Source references
references
  1. citation
    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.
    type
    BACKGROUND
  2. citation
    Sorrell AD, Alonzo TA, Hilden JM, Gerbing RB, Loew TW, Hathaway L, Barnard D, Taub JW, Ravindranath Y, Smith FO, Arceci RJ, Woods WG, Gamis AS. Favorable survival maintained in children who have myeloid leukemia associated with Down syndrome using reduced-dose chemotherapy on Children's Oncology Group trial A2971: a report from the Children's Oncology Group. Cancer. 2012 Oct 1;118(19):4806-14. doi: 10.1002/cncr.27484. Epub 2012 Mar 5.
    pmid
    22392565
    type
    RESULT
  3. citation
    Gamis AS, Alonzo TA, Gerbing RB, Hilden JM, Sorrell AD, Sharma M, Loew TW, Arceci RJ, Barnard D, Doyle J, Massey G, Perentesis J, Ravindranath Y, Taub J, Smith FO. Natural history of transient myeloproliferative disorder clinically diagnosed in Down syndrome neonates: a report from the Children's Oncology Group Study A2971. Blood. 2011 Dec 22;118(26):6752-9; quiz 6996. doi: 10.1182/blood-2011-04-350017. Epub 2011 Aug 17.
    pmid
    21849481
    type
    RESULT
  4. citation
    Gamis AS, Alonzo TA, Hilden JM, et al.: Outcome of Down syndrome (DS) children with acute myeloid leukemia (AML) or myelodysplasia (MDS) treated with a uniform prospective clinical trial initial report of the COG trial A2971. [Abstract] Blood 108 (11): A-15, 2006.
    type
    RESULT
  5. citation
    Sharma M, Alonzo TA, Sorrell A, et al.: Uniform approach better defines natural history of transient myeloproliferative disorder (TMD) in Down syndrome (DS) neonates: outcomes from Children's Oncology Group (COG) study A2971. [Abstract] Blood 108 (11): A-376, 2006.
    type
    RESULT
Source notices and limitations
    Discovery and provenance
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        cumulative anthracycline exposure from 320 mg to 240 mg), moving this cycle from intensification where it was used in the previous COG <a href="/clinicaltrials/NCT00003593">A2971 (NCT00003593)</a> trial.[<a href="#cit/section_4.10">10</a>,<a href="#cit/section_4.11">11</a>] Intrathecal doses were reduced from seven to two total i
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        line exposure from 320 mg to 240 mg), moving this cycle from intensification where it was used in the previous COG <a href="/clinicaltrials/NCT00003593">A2971 (NCT00003593)</a> trial.[<a href="#cit/section_4.10">10</a>,<a href="#cit/section_4.11">11</a>] Intrathecal doses were reduced from seven to two total injections, and inten
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      Childhood Myeloid Proliferations Associated With Down Syndrome Treatment (PDQ®)–Health Professional Version
      source update dates
      1. context
        Updated: September 16, 2024
        datetime
        2024-09-16T12:00:00Z
        display
        September 16, 2024

    Preserved source evidence · Not medical advice