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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT01824693




Registration number
NCT01824693
Ethics application status
Date submitted
2/04/2013
Date registered
5/04/2013
Date last updated
5/12/2018

Titles & IDs
Public title
Busulfan, Cyclophosphamide, and Melphalan or Busulfan and Fludarabine Phosphate Before Donor Hematopoietic Cell Transplant in Treating Younger Patients With Juvenile Myelomonocytic Leukemia
Scientific title
A Randomized Phase II Study Comparing Two Different Conditioning Regimens Prior to Allogeneic Hematopoietic Cell Transplantation (HCT) for Children With Juvenile Myelomonocytic Leukemia (JMML)
Secondary ID [1] 0 0
NCI-2013-00738
Secondary ID [2] 0 0
ASCT1221
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Juvenile Myelomonocytic Leukemia 0 0
Condition category
Condition code
Cancer 0 0 0 0
Leukaemia - Acute leukaemia
Cancer 0 0 0 0
Leukaemia - Chronic leukaemia
Cancer 0 0 0 0
Children's - Leukaemia & Lymphoma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Surgery - Allogeneic Hematopoietic Stem Cell Transplantation
Treatment: Drugs - Busulfan
Treatment: Drugs - Cyclophosphamide
Treatment: Drugs - Fludarabine Phosphate
Other interventions - Laboratory Biomarker Analysis
Treatment: Drugs - Melphalan
Treatment: Drugs - Mycophenolate Mofetil
Other interventions - Pharmacological Study
Treatment: Drugs - Tacrolimus

Experimental: Arm I (busulfan, cyclophosphamide, melphalan) - CONDITIONING REGIMEN: Patients receive busulfan IV QD, every 12 hours, or every 6 hours over 2-3 hours on days -8 to -5, cyclophosphamide IV QD over 60 minutes on days -4 and -3, and melphalan IV over 15-30 minutes on day -1.

TRANSPLANT: Patients undergo allogeneic HCT no sooner than 24 hours after the last dose of chemotherapy.

Patients receive tacrolimus IV or PO on days -1 to 98 (related donor) or 180 (unrelated donor) and mycophenolate mofetil IV over 2 hours or PO every 8 hours on days 1-30 (related donor) or 45 (unrelated donor).

Experimental: Arm II (busulfan, fludarabine phosphate) - CONDITIONING REGIMEN: Patients receive busulfan as in Arm I and fludarabine phosphate IV over 1 hour on days -5 to -2.

TRANSPLANT: Patients undergo allogeneic HCT as in Arm I.

Patients receive tacrolimus IV or PO on days -1 to 98 (related donor) or 180 (unrelated donor) and mycophenolate mofetil IV over 2 hours or PO every 8 hours on days 1-30 (related donor) or 45 (unrelated donor).


Treatment: Surgery: Allogeneic Hematopoietic Stem Cell Transplantation
Undergo allogeneic HCT

Treatment: Drugs: Busulfan
Given IV

Treatment: Drugs: Cyclophosphamide
Given IV

Treatment: Drugs: Fludarabine Phosphate
Given IV

Other interventions: Laboratory Biomarker Analysis
Correlative studies

Treatment: Drugs: Melphalan
Given IV

Treatment: Drugs: Mycophenolate Mofetil
Given IV or PO

Other interventions: Pharmacological Study
Correlative studies

Treatment: Drugs: Tacrolimus
Given IV or PO

Intervention code [1] 0 0
Treatment: Surgery
Intervention code [2] 0 0
Treatment: Drugs
Intervention code [3] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Percent Probability of Event-free Survival (EFS)
Timepoint [1] 0 0
From transplant up to 18 months
Primary outcome [2] 0 0
Number of Participants Who Experience Treatment-Related Mortality (TRM) by Day 100
Timepoint [2] 0 0
From transplant up to 100 days
Secondary outcome [1] 0 0
Percentage of Participants Who Experience Primary Graft Failure Event Between Arms
Timepoint [1] 0 0
Day 0 - day 540 (18 months) following completion of stem cell transplant
Secondary outcome [2] 0 0
Percent Probability of 18 Months-relapse Event Between Arms
Timepoint [2] 0 0
From transplant up to 18 months

Eligibility
Key inclusion criteria
* Patients must have a strong clinical suspicion of JMML, based on a modified category 1 of the revised diagnostic criteria; specifically, eligible patients must have all of the following:

* Splenomegaly
* Absolute monocyte count (AMC) > 1000/uL
* Blasts in peripheral blood (PB)/bone marrow (BM) < 20%
* For the 7-10% of patients without splenomegaly, the diagnostic entry criteria must include all other features described above and at least 2 of the following criteria:

* Circulating myeloid precursors
* White blood cell (WBC) > 10,000/uL
* Increased fetal hemoglobin (HgbF) for age
* Sargramostim (GM-CSF) hypersensitivity OR, patients must have been previously diagnosed with JMML
* Patients must be previously untreated with HCT
* All patients and/or their parents or legal guardians must sign a written informed consent
* All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met
Minimum age
3 Months
Maximum age
18 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Patients with a known germline mutation of PTPN11 (Noonan?s Syndrome) are not eligible
* Patients with a known history of NF1 (Neurofibromatosis Type 1) and either

* A history of a tumor of the central nervous system (astrocytoma or optic glioma), or
* A malignant peripheral nerve sheath tumor with a complete remission of < 1 year are not eligible
* Human immunodeficiency virus (HIV) positive patients are not eligible

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
WA
Recruitment hospital [1] 0 0
Princess Margaret Hospital for Children - Perth
Recruitment postcode(s) [1] 0 0
6008 - Perth
Recruitment outside Australia
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United States of America
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Alabama
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Arizona
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California
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Delaware
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Florida
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Georgia
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Illinois
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Indiana
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Iowa
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Kentucky
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Maryland
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Massachusetts
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Michigan
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Minnesota
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Mississippi
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Missouri
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Nebraska
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New Jersey
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New York
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Ohio
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Oklahoma
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Oregon
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Pennsylvania
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South Carolina
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Texas
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Utah
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Washington
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United States of America
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Wisconsin
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Canada
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British Columbia
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Canada
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Manitoba
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Canada
State/province [31] 0 0
Quebec
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New Zealand
State/province [32] 0 0
Auckland

Funding & Sponsors
Primary sponsor type
Other
Name
Children's Oncology Group
Address
Country
Other collaborator category [1] 0 0
Government body
Name [1] 0 0
National Cancer Institute (NCI)
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Christopher Dvorak
Address 0 0
Children's Oncology Group
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

No information has been provided regarding IPD availability


What supporting documents are/will be available?

Results publications and other study-related documents

No documents have been uploaded by study researchers.