Official Title: “Hematopoietic Cell Transplantation in Children With Juvenile Myelomonocytic Leukemia”

RATIONALE: Giving chemotherapy drugs, such as busulfan, cyclophosphamide, and melphalan, 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.

PURPOSE: This phase II trial is studying how well giving busulfan and cyclophosphamide together with melphalan works in treating young patients who are undergoing a donor bone marrow transplant or an umbilical cord transplant for juvenile myelomonocytic leukemia.

Study Type: Interventional

Study Design: Treatment, Open Label

OBJECTIVES:

Primary - Determine the long-term, disease-free survival of children with juvenile myelomonocytic leukemia treated with busulfan, cyclophosphamide, and melphalan followed by allogeneic hematopoietic cell transplantation.

Secondary - Determine the probability of engraftment in patients treated with this regimen. - Determine the incidence and severity of acute and chronic graft-versus-host disease in patients treated with this regimen. - Determine the incidence of regimen-related toxicity in these patients. - Determine the incidence of relapse in patients treated with this regimen.

OUTLINE: - Preparative therapy: Patients receive busulfan IV over 2 hours every 6 hours on days -7 to -4, cyclophosphamide IV over 2 hours on days -3 and -2, and melphalan IV over 30 minutes on day -1. Patients who undergo umbilical cord blood transplantation also receive anti-thymocyte globulin IV over 4-6 hours twice daily on days -3 to -1. - Allogeneic hematopoietic stem cell transplantation: Patients undergo allogeneic bone marrow or umbilical cord blood transplantation on day 0. - Post-transplant therapy: Patients receive cyclosporine IV 2-3 times daily on days -3 to 60 followed by a taper until approximately day 100. Patients who have an umbilical cord blood donor also receive mycophenolate mofetil IV on days 5-19. Patients who have a bone marrow donor also receive methotrexate IV on days 1, 3, 6, and 11. All patients receive oral isotretinoin once a day beginning on day 60 and continuing for 1 year.

After completion of study treatment, patients are followed periodically for survival.

PROJECTED ACCRUAL: A total of 10 patients will be accrued for this study.

Intervention(s) in this Clinical Trial

• Drug: anti-thymocyte globulin
• Drug: busulfan
• Drug: cyclophosphamide
• Drug: cyclosporine
• Drug: isotretinoin
• Drug: melphalan
• Drug: methotrexate
• Drug: mycophenolate mofetil
• Procedure: allogeneic bone marrow transplantation
• Procedure: umbilical cord blood transplantation

Primary Measures

• Disease-free survival at 1 year post transplantation
  • Safety Issue?: No

Secondary Measures

• Incidence of neutrophil engraftment, graft-versus-host disease (GVHD), regimen-related toxicity, and relapse post transplantation.
  • Safety Issue?: Yes

DISEASE CHARACTERISTICS:

• Diagnosis of juvenile myelomonocytic leukemia (JMML) meeting the following criteria:
• Leukocytosis (> 13,000/mm^3) with absolute monocytosis (> 1,000/mm^3)
• Presence of immature myeloid cells in the peripheral blood
• Less than 30% marrow blasts
• Absence of t(9:22) or BCR-ABL transcript
• Must have a HLA-matched, related or unrelated donor available, determined by class I antigens (HLA-A and -B) and class II antigens (DRB1 or DR [if parental typing available]), meeting one of the following criteria:
• 6/6 or 5/6 antigen match for bone marrow
• 6/6, 5/6, or 4/6 antigen match for umbilical cord blood

PATIENT CHARACTERISTICS:

• Performance status
• Karnofsky 70-100% OR
• Lansky 50-100%
• Life expectancy
• Not specified
• Hematopoietic
• See Disease Characteristics
• Hepatic
• No clinical evidence of hepatic failure (e.g., coagulopathy or ascites)
• Renal
• Creatinine < 2 times normal
• Cardiovascular
• LVEF ≥ 45% by MUGA or echocardiography
• Other
• No active uncontrolled infection

PRIOR CONCURRENT THERAPY:

• Not specified

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: N/A

Maximum Age for this Clinical Trial: 17 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: Masonic Cancer Center, University of Minnesota

Overall Clinical Trial Officials and Contacts

Margaret L. MacMillan, MD Study Chair Masonic Cancer Center, University of Minnesota  

Information obtained from ClinicalTrials.gov on September 04, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00262756

Study ID Number: CDR0000450983

ClinicalTrials.gov Identifier: NCT00262756

Health Authority: Unspecified

Clinical trial summary from the National Cancer Institute's PDQ® database