Clinical trial NCT00609739
Conditions: Leukemia
Keywords: juvenile myelomonocytic leukemia
Sponsor: Masonic Cancer Center, University of Minnesota
Start date: 1999-06-01; Completion date: 2010-06-01
Enrollment: 1 participants; Allocation: NON_RANDOMIZED; Intervention model: SINGLE_GROUP

Brief 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.

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.

Arms: arm 1: This is a phase I-II study designed to evaluate the efficacy of the administration of high dose cytosine arabinoside and mitoxantrone followed by HCT in patients with JMML who have residual disease or have relapsed after initial HCT.
Interventions: intervention 1: cyclosporine intervention 2: cytarabine intervention 3: filgrastim intervention 4: methotrexate intervention 5: methylprednisolone intervention 6: mitoxantrone hydrochloride intervention 7: allogeneic bone marrow transplantation intervention 8: umbilical cord blood transplantation intervention 9: Cis-Retinoic acid
Intervention descriptions: intervention 1: 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. intervention 2: 3000 mg/m\^2 intravenously (IV) over 2 hours x 2 (i.e. total 6000 mg/m\^2/day) on days -9 through -4. intervention 3: 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. intervention 4: 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. intervention 5: 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. intervention 6: 10 mg/m\^2 over 30 minutes intravenously (IV) on days -9 through -7. intervention 7: 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. intervention 8: 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. intervention 9: 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.

Protocol documents: