Stem Cell Transplant for Juvenile Myelomonocytic Leukemia (JMML)

Hematopoietic Cell Transplantation in Children With Juvenile Myelomonocytic Leukemia

The investigators hypothesize that long-term disease-free survival (DFS) in patients with JMML can be achieved with a treatment of busulfan (BU), cyclophosphamide (CY) and melphalan (L-PAM) followed by hematopoietic cell transplantation (HCT).

Study Overview

• Status: Completed
• Conditions: Juvenile Myelomonocytic Leukemia
• Intervention / Treatment: Biological: Stem Cell Transplant; Drug: Preparative Regimen

Detailed Description

Prior to transplantation, subjects will receive BUSULFAN via the central venous line, six times a day for four days, CYCLOPHOSPHAMIDE via the central venous line once a day for two days, and MELPHALAN via the central venous line for one day. Busulfan, cyclophosphamide, and melphalan are given to destroy the subject's leukemia. As well, these drugs will destroy the subject's own immune system to help ensure the new bone marrow takes and grows after transplantation.

On the day of transplantation, bone marrow or umbilical cord blood from the donor will arrive to the bone marrow transplant unit and be transfused via venous line. These new cells will replace the subject's bone marrow.

• Study Type: Interventional
• Enrollment (Actual): 15
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • Masonic Cancer Center, University of Minnesota

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 18 years (Child, Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients must have a diagnosis of JMML and fulfill these minimal criteria (International diagnostic criteria for JMML):

  • Leukocytosis (> 13,000) with absolute monocytosis (> 1,000)
  • The presence of immature myeloid cells in the peripheral blood
  • Less than 30% marrow blasts
  • Absence of t(9:22) or BCR-ABL transcript

  • Adequate major organ function including:

    • Cardiac: ejection fraction > 45%
    • Hepatic: no clinical evidence of hepatic failure (e.g. coagulopathy, ascites)
    • Karnofsky performance status > 70% or Lansky score > 50%
    • Creatinine must be < 2 x normal for age
• Written informed consent.

Exclusion Criteria:

• Active uncontrolled infection within one week of HCT.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intent-to-Treat; Patients receiving study regimen.	Biological: Stem Cell Transplant; Transplantation on Day 0.; Other Names: Bone marrow transplantation; Drug: Preparative Regimen; Busulfan; Cyclophosphamide; Mesna; Melphalan; Anti-thymocyte Globulin (ATG)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Determine Probability of Long-term Disease Free Survival in JMML	at 1 year after transplant

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Combined Incidence of Neutrophil Engraftment, Graft-versus-host Disease (GVHD), Regimen-related Toxicity, and Relapse.	Measured by AGVHD Grades 2 - 4.	at 1 year after transplant

Collaborators and Investigators

• Sponsor: Masonic Cancer Center, University of Minnesota
• Investigators: Principal Investigator: Margaret MacMillan, MD, Masonic Cancer Center, University of Minnesota

Study record dates

Study Major Dates

• Study Start (Actual): November 18, 1999
• Primary Completion (Actual): July 12, 2022
• Study Completion (Actual): August 9, 2023

Study Registration Dates

• First Submitted: September 9, 2005
• First Submitted That Met QC Criteria: September 9, 2005
• First Posted (Estimated): September 14, 2005

Study Record Updates

• Last Update Posted (Actual): November 7, 2023
• Last Update Submitted That Met QC Criteria: November 3, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: Stem cell transplant; retinoic acid; long term survival
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Histologic Type; Neoplasms; Disease Attributes; Bone Marrow Diseases; Hematologic Diseases; Myelodysplastic-Myeloproliferative Diseases; Leukemia, Myeloid; Chronic Disease; Leukemia; Leukemia, Myelomonocytic, Acute; Leukemia, Myelomonocytic, Chronic; Leukemia, Myelomonocytic, Juvenile
• Other Study ID Numbers: 1999LS073; MT1999-20 (Other Identifier: Blood and Marrow Transplant Program); 9911M24961 (Other Identifier: IRB, University of Minnesota)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No