NCT00025038

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

Trial Health

80
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
100

participants targeted

Target at P50-P75 for phase_2

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

June 1, 2001

Completed
4 months until next milestone

First Submitted

Initial submission to the registry

October 11, 2001

Completed
1.3 years until next milestone

First Posted

Study publicly available on registry

January 27, 2003

Completed
4.7 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

October 1, 2007

Completed
Last Updated

April 11, 2013

Status Verified

January 1, 2013

Enrollment Period

6.3 years

First QC Date

October 11, 2001

Last Update Submit

April 10, 2013

Conditions

Juvenile Myelomonocytic Leukemia

Outcome Measures

Primary Outcomes (5)

  • Response rate (CR or PR)

    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.

    Up to 6 years

  • Duration of response

    Will be estimated by Kaplan-Meier method.

    Up to 6 years

  • Progression-free survival

    Will be estimated by Kaplan-Meier method.

    2 years

  • Evaluation of prognostic importance of genetic marker

    Logrank test and Cox proportional hazards model will be applied.

    Up to 6 years

  • Grade 3 or greater toxicities assessed using CTC version 2.0

    Up to 6 years

Secondary Outcomes (2)

  • Survival of patients receiving the window vs. not

    Up to 6 years

  • Response status on end of course reports (pre vs.post)

    Up to 6 years

Study Arms (1)

Treatment (tipifarnib, bone marrow/umbilical cord transplant)

EXPERIMENTAL

See detailed description.

Drug: tipifarnibDrug: isotretinoinDrug: fludarabine phosphateDrug: cytarabineRadiation: radiation therapyDrug: cyclophosphamideBiological: anti-thymocyte globulinProcedure: allogeneic bone marrow transplantationProcedure: double-unit umbilical cord blood transplantationProcedure: umbilical cord blood transplantationOther: laboratory biomarker analysis

Interventions

tipifarnibDRUG

Given orally

Also known as: R115777, Zarnestra
Treatment (tipifarnib, bone marrow/umbilical cord transplant)
isotretinoinDRUG

Given orally

Also known as: 13-CRA, Amnesteem, Cistane, Claravis, Sotret
Treatment (tipifarnib, bone marrow/umbilical cord transplant)
fludarabine phosphateDRUG

Given IV

Also known as: 2-F-ara-AMP, Beneflur, Fludara
Treatment (tipifarnib, bone marrow/umbilical cord transplant)
cytarabineDRUG

Given IV

Also known as: ARA-C, arabinofuranosylcytosine, arabinosylcytosine, Cytosar-U, cytosine arabinoside
Treatment (tipifarnib, bone marrow/umbilical cord transplant)
radiation therapyRADIATION

Undergo total body irradiation

Also known as: irradiation, radiotherapy, therapy, radiation
Treatment (tipifarnib, bone marrow/umbilical cord transplant)
cyclophosphamideDRUG

Given IV

Also known as: CPM, CTX, Cytoxan, Endoxan, Endoxana
Treatment (tipifarnib, bone marrow/umbilical cord transplant)
anti-thymocyte globulinBIOLOGICAL

Given IV

Also known as: ATG, ATGAM, lymphocyte immune globulin, Thymoglobulin
Treatment (tipifarnib, bone marrow/umbilical cord transplant)
allogeneic bone marrow transplantationPROCEDURE

Undergo allogeneic bone marrow transplant

Also known as: bone marrow therapy, allogeneic, bone marrow therapy, allogenic, transplantation, allogeneic bone marrow, transplantation, allogenic bone marrow
Treatment (tipifarnib, bone marrow/umbilical cord transplant)
double-unit umbilical cord blood transplantationPROCEDURE
Treatment (tipifarnib, bone marrow/umbilical cord transplant)
umbilical cord blood transplantationPROCEDURE

Undergo allogeneic cord blood transplant

Also known as: cord blood transplantation, transplantation, umbilical cord blood, UCB transplantation
Treatment (tipifarnib, bone marrow/umbilical cord transplant)
laboratory biomarker analysisOTHER

Correlative studies

Treatment (tipifarnib, bone marrow/umbilical cord transplant)

Eligibility Criteria

AgeUp to 18 Years
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17), Adult (18-64)

You may qualify if:

  • 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)
  • +1 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Children's Oncology Group

Arcadia, California, 91006-3776, United States

Location

Related Publications (1)

  • 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: 37944074DERIVED

MeSH Terms

Conditions

Leukemia, Myelomonocytic, Juvenile

Interventions

tipifarnibIsotretinoinfludarabine phosphateCytarabineRadiotherapyRadiationCyclophosphamideAntilymphocyte SerumthymoglobulinTransplantationCord Blood Stem Cell Transplantation

Condition Hierarchy (Ancestors)

Leukemia, MyeloidLeukemiaNeoplasms by Histologic TypeNeoplasmsMyelodysplastic-Myeloproliferative DiseasesBone Marrow DiseasesHematologic DiseasesHemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

RetinoidsCarotenoidsPolyenesAlkenesHydrocarbons, AcyclicHydrocarbonsOrganic ChemicalsCyclohexenesCyclohexanesCycloparaffinsHydrocarbons, AlicyclicHydrocarbons, CyclicTerpenesPigments, BiologicalBiological FactorsCytidinePyrimidine NucleosidesPyrimidinesHeterocyclic Compounds, 1-RingHeterocyclic CompoundsArabinonucleosidesNucleosidesNucleic Acids, Nucleotides, and NucleosidesTherapeuticsPhysical PhenomenaPhosphoramide MustardsNitrogen Mustard CompoundsMustard CompoundsHydrocarbons, HalogenatedPhosphoramidesOrganophosphorus CompoundsImmune SeraAntibodiesImmunoglobulinsImmunoproteinsBlood ProteinsProteinsAmino Acids, Peptides, and ProteinsSerum GlobulinsGlobulinsBiological ProductsComplex MixturesSurgical Procedures, OperativeStem Cell TransplantationCell TransplantationCell- and Tissue-Based TherapyBiological Therapy

Study Officials

  • Robert Castleberry

    Children's Oncology Group

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 2
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
NIH
Responsible Party
SPONSOR

Study Record Dates

First Submitted

October 11, 2001

First Posted

January 27, 2003

Study Start

June 1, 2001

Primary Completion

October 1, 2007

Last Updated

April 11, 2013

Record last verified: 2013-01

Locations

US(1)