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

Sponsors and Collaborators:	Masonic Cancer Center, University of Minnesota National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00609739

Purpose

RATIONALE: Giving chemotherapy drugs, such as cytarabine and mitoxantrone, before a donor stem cell transplant helps stop the growth of cancer cells and helps stop the patient's immune system from rejecting the donor's stem cells. When certain 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. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells. Giving cyclosporine, methotrexate, and methylprednisolone before or after transplant may stop this from happening.

PURPOSE: This phase I/II trial is studying the side effects and best way to give high-dose cytarabine together with mitoxantrone in treating patients with juvenile myelomonocytic leukemia undergoing a second donor stem cell transplant.

Condition	Intervention	Phase
Leukemia	Drug: cyclosporine Drug: cytarabine Drug: isotretinoin Drug: methotrexate Drug: methylprednisolone Drug: mitoxantrone hydrochloride Procedure: allogeneic bone marrow transplantation Procedure: allogeneic hematopoietic stem cell transplantation Procedure: umbilical cord blood transplantation	Phase I Phase II

Study Type:	Interventional
Study Design:	Treatment, Open Label
Official Title:	Cytosine Arabinoside and Mitoxantrone for Patients With Juvenile Myelomonocytic Leukemia Receiving Repeat Stem Cell Transplantation

Resource links provided by NLM:

MedlinePlus related topics: Bone Marrow Transplantation Cancer Leukemia, Adult Acute Leukemia, Adult Chronic Leukemia, Childhood

Drug Information available for: Methotrexate Cytarabine hydrochloride Cyclosporine Mitoxantrone Mitoxantrone hydrochloride Cyclosporin Methylprednisolone Cytarabine Isotretinoin

U.S. FDA Resources

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

1-year disease-free survival [ Designated as safety issue: No ]

Secondary Outcome Measures:

Incidence of regimen-related toxicity [ Designated as safety issue: Yes ]
Incidence of acute and chronic graft-versus-host-disease [ Designated as safety issue: No ]
Incidence of relapse [ Designated as safety issue: No ]

Estimated Enrollment:	10
Study Start Date:	June 1999
Estimated Primary Completion Date:	January 2013 (Final data collection date for primary outcome measure)

Detailed Description:

OBJECTIVES:

Primary

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

To evaluate the incidence of regimen-related toxicity.
To evaluate the incidence of acute and chronic graft-versus-host-disease.
To evaluate the 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 60 and continuing until 1 year after HSCT. Patients undergo bone marrow sample collection on day 21, day 60, 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.

Eligibility

Ages Eligible for Study:	up to 18 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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 10^8/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 10^7 nucleated cells/kg patient body weight

PATIENT CHARACTERISTICS:

Karnofsky performance status (PS) 70-100% or Lansky PS 50-100%
Ejection fraction ≥ 45%
FEV_1 > 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

PRIOR CONCURRENT THERAPY:

See Disease Characteristics

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00609739

Locations

United States, Minnesota
Masonic Cancer Center at University of Minnesota	Recruiting
Minneapolis, Minnesota, United States, 55455
Contact: Clinical Trials Office - Masonic Cancer Center at University o 612-624-2620

Sponsors and Collaborators

Masonic Cancer Center, University of Minnesota

National Cancer Institute (NCI)

Investigators

Principal Investigator:

Margaret L. MacMillan, MD

Masonic Cancer Center, University of Minnesota

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	Masonic Cancer Center at University of Minnesota ( Margaret L. MacMillan )
Study ID Numbers:	CDR0000586078, UMN-1999LS032, UMN-MT1999-08
Study First Received:	February 6, 2008
Last Updated:	April 2, 2009
ClinicalTrials.gov Identifier:	NCT00609739 History of Changes
Health Authority:	Unspecified

Keywords provided by National Cancer Institute (NCI):

juvenile myelomonocytic leukemia

Study placed in the following topic categories:

Anti-Inflammatory Agents
Antimetabolites
Chronic Myelomonocytic Leukemia
Cyclosporine
Immunologic Factors
Methylprednisolone
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Folate
Antiemetics
Prednisolone acetate
Hormones
Neuroprotective Agents
Cyclosporins
Vitamin B9

Leukemia
Antifungal Agents
Isotretinoin
Methotrexate
Analgesics
Cytarabine
Myelodysplastic Myeloproliferative Disease
Methylprednisolone Hemisuccinate
Antineoplastic Agents, Hormonal
Hematologic Diseases
Leukemia, Myelomonocytic, Chronic
Myeloproliferative Disorders
Juvenile Myelomonocytic Leukemia
Methylprednisolone acetate
Leukemia, Myeloid

Additional relevant MeSH terms:

Anti-Inflammatory Agents
Anti-Infective Agents
Cyclosporine
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Methylprednisolone
Physiological Effects of Drugs
Hormones, Hormone Substitutes, and Hormone Antagonists
Antiemetics
Hormones
Cyclosporins
Therapeutic Uses
Abortifacient Agents
Methotrexate
Dermatologic Agents

Nucleic Acid Synthesis Inhibitors
Methylprednisolone Hemisuccinate
Antineoplastic Agents, Hormonal
Hematologic Diseases
Leukemia, Myelomonocytic, Chronic
Leukemia, Myeloid
Abortifacient Agents, Nonsteroidal
Glucocorticoids
Neoplasms
Mitoxantrone
Antimetabolites
Immunologic Factors
Antineoplastic Agents
Prednisolone acetate
Reproductive Control Agents

ClinicalTrials.gov processed this record on July 02, 2009