Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Trial Contact Information
Registry Information

Alternate Title

High-Dose Cytarabine and Mitoxantrone in Treating Patients With Juvenile Myelomonocytic Leukemia Undergoing a Second Donor Stem Cell Transplant

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase II, Phase I Treatment Active Juvenile NCI UMN-1999LS032 UMN-1999LS032, UMN-MT1999-08, NCT00609739

Objectives

Primary

1. To determine the incidence of 1-year disease-free survival in patients with juvenile myelomonocytic leukemia and who is undergoing a repeat stem cell transplantation.

Secondary

1. To evaluate the incidence of regimen-related toxicity.
2. To evaluate the incidence of acute and chronic graft-versus-host-disease.
3. To evaluate the incidence of relapse.

Entry Criteria

Disease Characteristics:

• Diagnosis of juvenile myelomonocytic leukemia (JMML)



• Relapsed or residual disease after initial allogeneic hematopoietic stem cell transplantation (HSCT)
  • Relapsed* disease as evidence by the reappearance of all of the following:
    • Leukocytosis with absolute monocytosis > 1 x 10⁸/L
    • Presence of immature myeloid cells in the peripheral circulation in two consecutive bone marrow specimens taken ≥ 1 month apart
    • Presence of clonal cytogenetic abnormalities

     [Note: *Diagnosis of relapse will be supported by the return of an abnormal cytogenetic marker (if present at diagnosis) or the presence of host cells by restriction fragment length polymorphism or other method.]

  • Residual disease is defined as failure to eradicate original disease without prior documentation of remission



• Patients should be ≥ 6 months from first HSCT, if clinically stable
  • In patients with rapidly progressive JMML, second HSCT may be performed earlier



• Available donor should be the same type as used in the initial HSCT or a greater HLA-disparate donor to enhance possibility of graft-versus-leukemia



• Stem cell source may be allogeneic bone marrow or umbilical cord blood
  • Cord blood units selected for transplantation must contain ≥ 1 x 10⁷ nucleated cells/kg patient body weight

Prior/Concurrent Therapy:

• See Disease Characteristics

Patient Characteristics:

• Karnofsky performance status (PS) 70-100% or Lansky PS 50-100%
• Ejection fraction ≥ 45%
• FEV₁ > 50%
• DLCO > 50%
• Creatinine clearance ≥ 40 mL/min
• No clinical evidence of hepatic failure (e.g., coagulopathy or ascites)
• No active uncontrolled infection within 1 week of HSCT

Expected Enrollment

Outcomes

1-year disease-free survival

Incidence of regimen-related toxicity
Incidence of acute and chronic graft-versus-host-disease
Incidence of relapse

Outline

• Preparative cytoreductive therapy: Patients receive high-dose cytarabine IV over 2 hours on days -9 to -4 and mitoxantrone hydrochloride IV over 30 minutes on days -9 to -7.



• Allogeneic hematopoietic stem cell transplantation (HSCT): Patients undergo HSCT on day 0. Patients undergoing umbilical cord blood transplantation receive methylprednisolone (as graft failure prophylaxis) IV twice daily on days 5 to 19 followed by a taper every other day thereafter until day 25.



• Graft-versus-host-disease (GVHD) prophylaxis: Patients receive cyclosporine IV over 2 hours every 8-12 hours or orally twice daily beginning on day -3 and continuing until day 50, followed by a taper to day 90, in the absence of GVHD. Patients undergoing nongenotypically identical bone marrow transplantation also receive methotrexate IV on day 1 beginning 24 hours after completion of stem cell infusion and on days 3, 6, and 11.



• Post-transplantation isotretinoin therapy: Patients receive oral isotretinoin once daily beginning on day 50 and continuing until 1 year after HSCT.

Patients undergo bone marrow sample collection on day 21, day 100, at 6 months, and at 1 year for chimerism studies. Patients also undergo blood sample collection periodically to monitor peripheral blood counts for immune reconstitution.

After completion of study treatment, patients are followed on day 21, day 100, at 6 months, and at 1 year.

Trial Contact Information

Trial Lead Organizations

Masonic Cancer Center at University of Minnesota

Margaret MacMillan, MD, Principal investigator		Ph: 612-626-2778; 888-226-2376 Email: macmi002@umn.edu

U.S.A.
Minnesota
	Minneapolis
	Masonic Cancer Center at University of Minnesota
		Clinical Trials Office - Masonic Cancer Center at University of Minnesota	Ph:  612-624-2620

Registry Information
Official Title		Cytosine Arabinoside and Mitoxantrone for Patients with Juvenile Myelomonocytic Leukemia Receiving Repeat Stem Cell Transplantation
Trial Start Date		1999-06-17
Trial Completion Date		2013-01-07 (estimated)
Registered in ClinicalTrials.gov		NCT00609739
Date Submitted to PDQ		2008-01-22
Information Last Verified		2008-09-12
NCI Grant/Contract Number		CA77598