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NCT00025038 · CITED IN SOURCE DOCUMENTS

Combination Chemotherapy Followed By Donor Bone Marrow or Umbilical Cord Blood Transplant in Treating Children With Newly Diagnosed Juvenile Myelomonocytic Leukemia

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

Phase
PHASE2
Status at capture
COMPLETED
Registry last update
2013-04-11

Giving chemotherapy drugs, such as R115777, isotretinoin, cytarabine, and fludarabine, before a donor bone marrow transplant or an umbilical cord transplant helps stop the growth of cancer cells. It also helps stop the patient's immune system from rejecting the donor's stem cells. When the healthy stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. This phase II trial is studying how well giving combination chemotherapy together with donor bone marrow or umbilical cord blood transplant works in treating children with newly diagnosed juvenile myelomonocytic leukemia

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
Inclusion Criteria: * Newly diagnosed, previously untreated juvenile myelomonocytic leukemia * Presenting with all of the following: * Absence of t(9;22) or bcr/abl by PCR * Absolute monocyte count greater than 1,000/mm\^3 * Less than 20% bone marrow blasts * Presenting with at least 2 of the following: * Elevated F hemoglobin * Myeloid precursors in peripheral blood * WBC greater than 10,000/mm\^3 * Sargramostim (GM-CSF) hypersensitivity * See Disease Characteristics * Bilirubin no greater than 2.0 mg/dL * ALT no greater than 3 times normal * Creatinine no greater than 2 times normal * No concurrent sargramostim (GM-CSF) * No concurrent proton pump inhibitors
healthy Volunteers
false
maximum Age
18 Years
sex
ALL
std Ages
  1. CHILD
  2. ADULT
Treatment arms and interventions
arm Groups
  1. description
    See detailed description.
    intervention Names
    1. Drug: tipifarnib
    2. Drug: isotretinoin
    3. Drug: fludarabine phosphate
    4. Drug: cytarabine
    5. Radiation: radiation therapy
    6. Drug: cyclophosphamide
    7. Biological: anti-thymocyte globulin
    8. Procedure: allogeneic bone marrow transplantation
    9. Procedure: double-unit umbilical cord blood transplantation
    10. Procedure: umbilical cord blood transplantation
    11. Other: laboratory biomarker analysis
    label
    Treatment (tipifarnib, bone marrow/umbilical cord transplant)
    type
    EXPERIMENTAL
interventions
  1. arm Group Labels
    1. Treatment (tipifarnib, bone marrow/umbilical cord transplant)
    description
    Given orally
    name
    tipifarnib
    other Names
    1. R115777
    2. Zarnestra
    type
    DRUG
  2. arm Group Labels
    1. Treatment (tipifarnib, bone marrow/umbilical cord transplant)
    description
    Given orally
    name
    isotretinoin
    other Names
    1. 13-CRA
    2. Amnesteem
    3. Cistane
    4. Claravis
    5. Sotret
    type
    DRUG
  3. arm Group Labels
    1. Treatment (tipifarnib, bone marrow/umbilical cord transplant)
    description
    Given IV
    name
    fludarabine phosphate
    other Names
    1. 2-F-ara-AMP
    2. Beneflur
    3. Fludara
    type
    DRUG
  4. arm Group Labels
    1. Treatment (tipifarnib, bone marrow/umbilical cord transplant)
    description
    Given IV
    name
    cytarabine
    other Names
    1. ARA-C
    2. arabinofuranosylcytosine
    3. arabinosylcytosine
    4. Cytosar-U
    5. cytosine arabinoside
    type
    DRUG
  5. arm Group Labels
    1. Treatment (tipifarnib, bone marrow/umbilical cord transplant)
    description
    Undergo total body irradiation
    name
    radiation therapy
    other Names
    1. irradiation
    2. radiotherapy
    3. therapy, radiation
    type
    RADIATION
  6. arm Group Labels
    1. Treatment (tipifarnib, bone marrow/umbilical cord transplant)
    description
    Given IV
    name
    cyclophosphamide
    other Names
    1. CPM
    2. CTX
    3. Cytoxan
    4. Endoxan
    5. Endoxana
    type
    DRUG
  7. arm Group Labels
    1. Treatment (tipifarnib, bone marrow/umbilical cord transplant)
    description
    Given IV
    name
    anti-thymocyte globulin
    other Names
    1. ATG
    2. ATGAM
    3. lymphocyte immune globulin
    4. Thymoglobulin
    type
    BIOLOGICAL
  8. arm Group Labels
    1. Treatment (tipifarnib, bone marrow/umbilical cord transplant)
    description
    Undergo allogeneic bone marrow transplant
    name
    allogeneic bone marrow transplantation
    other Names
    1. bone marrow therapy, allogeneic
    2. bone marrow therapy, allogenic
    3. transplantation, allogeneic bone marrow
    4. transplantation, allogenic bone marrow
    type
    PROCEDURE
  9. arm Group Labels
    1. Treatment (tipifarnib, bone marrow/umbilical cord transplant)
    name
    double-unit umbilical cord blood transplantation
    type
    PROCEDURE
  10. arm Group Labels
    1. Treatment (tipifarnib, bone marrow/umbilical cord transplant)
    description
    Undergo allogeneic cord blood transplant
    name
    umbilical cord blood transplantation
    other Names
    1. cord blood transplantation
    2. transplantation, umbilical cord blood
    3. UCB transplantation
    type
    PROCEDURE
  11. arm Group Labels
    1. Treatment (tipifarnib, bone marrow/umbilical cord transplant)
    description
    Correlative studies
    name
    laboratory biomarker analysis
    type
    OTHER
Study design
allocation
NA
intervention Model
SINGLE_GROUP
masking Info
masking
NONE
primary Purpose
TREATMENT
Enrollment
count
100
type
ACTUAL
Registered outcome plans (not posted results)
primary Outcomes
  1. description
    The response rates in the up-front window with respect to whether or not patients had vas activating mutations will also be estimated by proportions.
    measure
    Response rate (CR or PR)
    time Frame
    Up to 6 years
  2. description
    Will be estimated by Kaplan-Meier method.
    measure
    Duration of response
    time Frame
    Up to 6 years
  3. description
    Will be estimated by Kaplan-Meier method.
    measure
    Progression-free survival
    time Frame
    2 years
  4. description
    Logrank test and Cox proportional hazards model will be applied.
    measure
    Evaluation of prognostic importance of genetic marker
    time Frame
    Up to 6 years
  5. measure
    Grade 3 or greater toxicities assessed using CTC version 2.0
    time Frame
    Up to 6 years
secondary Outcomes
  1. measure
    Survival of patients receiving the window vs. not
    time Frame
    Up to 6 years
  2. description
    Signed-rank comparison of components of therapy will be done.
    measure
    Response status on end of course reports (pre vs.post)
    time Frame
    Up to 6 years
Full study description
brief Summary
Giving chemotherapy drugs, such as R115777, isotretinoin, cytarabine, and fludarabine, before a donor bone marrow transplant or an umbilical cord transplant helps stop the growth of cancer cells. It also helps stop the patient's immune system from rejecting the donor's stem cells. When the healthy stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. This phase II trial is studying how well giving combination chemotherapy together with donor bone marrow or umbilical cord blood transplant works in treating children with newly diagnosed juvenile myelomonocytic leukemia
detailed Description
PRIMARY OBJECTIVES: I. Determine the response rate of children with newly diagnosed juvenile myelomonocytic leukemia treated with R115777, isotretinoin, cytarabine, and fludarabine followed by allogeneic bone marrow or umbilical cord blood transplantation. II. Determine the safety and toxicity of this regimen in these patients. III. Determine the tolerability of this regimen in these patients. IV. Determine the rate of 2-year event-free survival of patients treated with this regimen. V. Determine whether prognostic subsets of these patients can be identified based on expression of clinical, genetic (NFI, monosomy 7, RAS gene), or hematopoietic characteristics. OUTLINE: This is a multicenter study. Patients may choose to receive upfront window induction therapy with oral R115777 twice daily on days 1-21. Treatment repeats every 28 days for 2 courses in the absence of disease progression or unacceptable toxicity. Patients with progressive disease or stable disease with unacceptable hematopoietic recovery after 1 course proceed to induction chemotherapy. (R11577 portion of the study closed to accrual as of 08/2005) All patients receive induction chemotherapy comprising oral isotretinoin once daily beginning on day 1 and fludarabine IV over 30 minutes and cytarabine IV over 4 hours on days 1-5. Treatment with fludarabine and cytarabine repeats every 28 days for 2 courses. Treatment with isotretinoin continues until allogeneic bone marrow or umbilical cord blood transplantation. Patients with progressive disease after 1 course proceed to transplantation. After completion of isotretinoin, patients receive a preparative regimen comprising total body irradiation twice daily on days -7 to -4, cyclophosphamide IV over 2 hours on days -3 and -2, and anti-thymocyte globulin IV over 4-6 hours every 12 hours on days -3 to -1. Patients undergo allogeneic bone marrow or umbilical cord blood transplantation on day 0. Patients receive oral isotretinoin daily beginning on approximately day 60 and continuing for 1 year. Patients are followed every 6 months for 5 years and then annually thereafter. PROJECTED ACCRUAL: A maximum of 100 patients (18-46 receiving R115777 with induction chemotherapy \[R11577 portion of the study closed to accrual as of 08/2005\] and 27-54 receiving induction chemotherapy only) will be accrued for this study within 3.2 years.
Source references
references
  1. citation
    Stieglitz E, Gu CJ, Richardson M, Kita R, Santaguida MT, Ali KA, Strachan DC, Dhar A, Yam G, Anderson W, Anderson E, Hubner J, Tasian SK, Loh ML, Lacher MD. Tretinoin Enhances the Effects of Chemotherapy in Juvenile Myelomonocytic Leukemia Using an Ex Vivo Drug Sensitivity Assay. JCO Precis Oncol. 2023 Sep;7:e2300302. doi: 10.1200/PO.23.00302.
    pmid
    37944074
    type
    DERIVED
Source notices and limitations
    Discovery and provenance
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        oin alone was given for two cycles before planned HSCT in 34 of 87 evaluable children with JMML in the Children's Oncology Group (COG) <a href="/clinicaltrials/NCT00025038">AAML0122</a> trial.[<a href="#cit/section_9.3">3</a>]<div class="pdq-content-list"><ul id="_2027"><li>In this group, the overall response rate (partial respon
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      source title
      Juvenile Myelomonocytic Leukemia Treatment (PDQ®)–Health Professional Version
      source update dates
      1. context
        Updated: December 10, 2024
        datetime
        2024-12-10T12:00:00Z
        display
        December 10, 2024

    Preserved source evidence · Not medical advice