Cytosine Arabinoside and Mitoxantrone for Patients With Juvenile Myelomonocytic Leukemia Receiving Repeat Stem Cell Transplantation

Summary

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.

Conditions

• Leukemia

Interventions

DRUG

cyclosporine

Patients will receive CSA therapy beginning on day -3, with a taper commencing on day +60 (unless GVHD) and ending on day +90. For patients \>40 kg with normal renal function (creatinine \<1.3 mg/dL), the initial dose will be 2.5 mg/kg intravenously (IV) over 2 hours every 12 hours. For children \<40 kg, the initial dose will be 2.5 mg/kg IV over 2 hours every 8 hours.

DRUG

cytarabine

3000 mg/m\^2 intravenously (IV) over 2 hours x 2 (i.e. total 6000 mg/m\^2/day) on days -9 through -4.

DRUG

filgrastim

Patients with absolute neutrophil count (ANC) \<0.2 x 10\^8/L on day 21 may receive G-CSF at 5 mcg/kg/day. G-CSF will be continued until ANC ≥2.5 x 10\^8/L for two consecutive days. As the malignant cell population of JMML is known to be hypersensitive to GM-CSF, this cytokine will not be given to these patients.

DRUG

methotrexate

MTX will be administered to recipients of non-genotypically identical BMT. MTX will be administered at a dose of 15 mg/m\^2 (based on adjusted ideal body weight) intravenously (IV) on day +1 and at a dose of 10 mg/m\^2 IV on days +3, +6, and +11.

DRUG

methylprednisolone

Recipients of UCB will receive methylprednisolone 2 mg/kg/day from day +5 to +19 at a dose of 1 mg/kg twice a day (bid) with a 10% taper every week thereafter.

DRUG

mitoxantrone hydrochloride

10 mg/m\^2 over 30 minutes intravenously (IV) on days -9 through -7.

PROCEDURE

allogeneic bone marrow transplantation

Donor marrow will be collected in the usual sterile manner with a collection goal of 2.0 \>10\^8/kg recipient weight. Infused on Day 0.

PROCEDURE

umbilical cord blood transplantation

Umbilical cord blood (UCB) will be cryopreserved prior to transplantation. Cord blood units will be selected for transplantation according to current University of Minnesota Department of Blood and Marrow Transplantation Guidelines.

DRUG

Cis-Retinoic acid

Post-Transplant Cis-Retinoic Acid (CRA) Therapy - CRA will be given at a dosage of 100 mg/m\^2/day by mouth in a single daily dose starting on day +60 and continuing until 1 year after transplant.

Sponsors & Collaborators

• Masonic Cancer Center, University of Minnesota

  lead OTHER

Principal Investigators

• Margaret L. MacMillan, MD · Masonic Cancer Center, University of Minnesota

Study Design

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Max Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

1999-06-30

Primary Completion

2010-06-30

Completion

2010-06-30

Countries

• United States

Study Locations