Children's Oncology Group (COG) JMML Clinical Trial:  ASCT1221

Update 4 December 2015:  This trial is no longer enrolling new patients.

Busulfan, Cyclophosphamide, and Melphalan or Busulfan and Fludarabine Phosphate Before Donor Hematopoietic Cell Transplant in Treating Younger Patients With Juvenile Myelomonocytic Leukemia (NCT01824693)

Juvenile Myelomonocytic Leukemia (JMML) is a particularly rare and deadly form of pediatric leukemia that typically has  no cure short of a Stem Cell Transplant (SCT). Given that JMML is not well understood, nor is the optimal treatment for JMML well established, much of the current research into JMML emphasizes improving treatment outcomes or better understanding the cause of the disease.

This clinical trial, which is funded by the National Cancer Institute and led by the Children’s Oncology Group, is currently being conducted at 47 hospitals and research centers across North America (see the JMML Treatment Centers map for institutions denoted as "JMML Clinical Trial Participant"). Please ask your child’s doctor if they have the trial open at your child’s hospital.

In the ASCT1221 study, two approaches to SCT will be compared to see which is better for treating JMML while causing the fewest unwanted side effects. Another goal of this study is to learn more about the biology and characteristics of JMML, which is a difficult disease to diagnose, making it crucial to have a correct diagnosis before treatment with a SCT is undertaken.

Recent developments in laboratories around the world have led to discoveries about the changes in the genes (otherwise known as DNA) in patients with JMML. These changes are also called mutations, and can be helpful in making the diagnosis of JMML and in predicting the severity of disease. While it is possible to have JMML without having a mutation in one of these genes, it is unlikely. Fewer than 15% of children with JMML have no identified change in the genes called PTPN11, NRAS, KRAS, or CBL, or have clinical neurofibromatosis.

This study has two parts:

In Part 1, the diagnosis of JMML will be confirmed. Study subjects and their parents will have samples collected for diagnostic testing. Samples will be sent for testing in a laboratory at the University of California, San Francisco (UCSF). This laboratory specializes in confirming the diagnosis of JMML. Tests will be done to see if certain genes are mutated. Samples will also be collected for medical research studies to learn more about JMML.

In Part 2, children with a confirmed JMML diagnosis as well as an appropriate stem cell donor will be treated with a SCT. A SCT is standard or regular therapy for people with JMML. The most common SCT conditioning regimen for JMML patients in North America uses the drugs busulfan and cyclophosphamide (also known as "BU-CY"). Sometimes a third drug called melphalan is added to the regimen (known as "BU-CY-MEL"). Another SCT conditioning regimen uses the drugs busulfan and fludarabine (also known as "BU-FLU"). There is little information regarding the BU-FLU regimen in JMML patients. However, in patients with other forms of leukemia it is thought to cause fewer side effects than the BU-CY regimen. Study doctors want to see if the BU-FLU regimen results in the same cure rates as the BU-CY-MEL regimen, without as many of the side effects.

Summary of Study Treatments 

In this study the patient will get 1 of 2 SCT conditioning regimens. The 2 treatment plans are called Arm A and Arm B, as follows:

  • Arm A: SCT with a BU-CY-MEL conditioning regimen.
  • Arm B: SCT with a BU-FLU conditioning regimen.

Random Assignment
The patient will receive 1 of the 2 treatment plans described above. The treatment plan that the patient receives is decided by a process called randomization. Randomization means that the treatment is assigned based on chance. It is a lot like flipping a coin, except that it is done by computer. You and your child’s doctor will not pick which treatment you get.

COG Resources

For more about the Children’s Oncology Group, it’s mission, and what a clinical trial entails, please visit their website:


If you or your child’s doctors have questions about the ASCT1221 trial, please contact the trial’s principal investigators:

  • Christopher C. Dvorak, MD, University of California Benioff Children’s Hospital:

            Phone: (415) 476-2188


  • Prakash Satwani, MD, Columbia University:

            Phone: (212) 305-8316


The information on this page was last reviewed in December 2015 by Dr. Christopher C. Dvorak, Benioff Children’s Hospital, University of California San Francisco, San Francisco, CA

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