Cytosine Arabinoside and Mitoxantrone for Patients With Juvenile Myelomonocytic Leukemia Receiving Repeat Stem Cell Transplantation
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.
Drug: mitoxantrone hydrochloride
Procedure: allogeneic bone marrow transplantation
Procedure: umbilical cord blood transplantation
Drug: Cis-Retinoic acid
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Cytosine Arabinoside and Mitoxantrone for Patients With Juvenile Myelomonocytic Leukemia Receiving Repeat Stem Cell Transplantation|
- Disease-free Survival [ Time Frame: 1 year ] [ Designated as safety issue: No ]Number of patients who were free of disease and alive at 1 year.
- Patients With Regimen-Related Toxicity [ Time Frame: Up to 30 Days Post Study Treatment ] [ Designated as safety issue: Yes ]Number of patients with adverse events related to treatment.
- Patients With Graft-Versus-Host-Disease [ Time Frame: Up to 30 Days Post Study Treatment ] [ Designated as safety issue: No ]Number of patients who exhibited acute and/or chronic graft-versus-host disease.
- Patients Who Relapsed [ Time Frame: 1 Year ] [ Designated as safety issue: No ]Number of patients whose disease relapsed.
|Study Start Date:||June 1999|
|Study Completion Date:||June 2010|
|Primary Completion Date:||June 2010 (Final data collection date for primary outcome measure)|
Experimental: Cytarabine + Mitoxantrone
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.
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.
Other Name: CSADrug: 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.
Other Name: Ara-CDrug: 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.
Other Name: G-CSFDrug: 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.
Other Name: MTXDrug: 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.
Other Name: MedrolDrug: mitoxantrone hydrochloride
10 mg/m^2 over 30 minutes intravenously (IV) on days -9 through -7.
Other Name: MitoxantroneProcedure: 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.
Other Name: isotretinoin
- 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.
- 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.
- 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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00609739
|United States, Minnesota|
|Masonic Cancer Center at University of Minnesota|
|Minneapolis, Minnesota, United States, 55455|
|Principal Investigator:||Margaret L. MacMillan, MD||Masonic Cancer Center, University of Minnesota|