Cytosine Arabinoside and Mitoxantrone for Patients With Juvenile Myelomonocytic Leukemia Receiving Repeat Stem Cell Transplantation
- Conditions
- Leukemia
- Interventions
- Procedure: allogeneic bone marrow transplantationProcedure: umbilical cord blood transplantationDrug: Cis-Retinoic acid
- Registration Number
- NCT00609739
- Lead Sponsor
- Masonic Cancer Center, University of Minnesota
- 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.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 1
-
Patients age 0-18 with juvenile myelomonocytic leukemia (JMML) who have relapsed or have residual disease after allogeneic HCT. Residual disease is defined as failure to eradicate original disease without prior documentation of remission. Relapse is defined as reappearance of i) leukocytosis with absolute monocytosis >1 x 10^8/L, ii) presence of immature myeloid cells in the peripheral circulation in two consecutive bone marrow specimens taken at least one month apart, or iii) presence of clonal cytogenetic abnormality. The 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 RFLP or other method.
-
Patients should be at least 6 months from first hematopoietic cell transplant (HCT) if clinically stable. (If JMML is rapidly progressive, second HCT may be performed earlier).
-
Adequate major organ function including:
- Cardiac: ejection fraction ≥45%
- Pulmonary: FEV >50%, DLCO >50%
-
Renal: creatinine clearance ≥40 mL/min
- Hepatic: no clinical evidence of hepatic failure (e.g. coagulopathy, ascites)
-
Karnofsky performance status ≥70% or Lansky score ≥50%
-
-
Written informed consent.
- Active uncontrolled infection within one week of HCT.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Cytarabine + Mitoxantrone mitoxantrone hydrochloride 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. Cytarabine + Mitoxantrone Cis-Retinoic acid 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. Cytarabine + Mitoxantrone allogeneic bone marrow transplantation 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. Cytarabine + Mitoxantrone umbilical cord blood transplantation 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. Cytarabine + Mitoxantrone cytarabine 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. Cytarabine + Mitoxantrone cyclosporine 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. Cytarabine + Mitoxantrone filgrastim 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. Cytarabine + Mitoxantrone methotrexate 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. Cytarabine + Mitoxantrone methylprednisolone 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.
- Primary Outcome Measures
Name Time Method Disease-free Survival 1 year Number of patients who were free of disease and alive at 1 year.
- Secondary Outcome Measures
Name Time Method Patients With Graft-Versus-Host-Disease Up to 30 Days Post Study Treatment Number of patients who exhibited acute and/or chronic graft-versus-host disease.
Patients With Regimen-Related Toxicity Up to 30 Days Post Study Treatment Number of patients with adverse events related to treatment.
Patients Who Relapsed 1 Year Number of patients whose disease relapsed.
Trial Locations
- Locations (1)
Masonic Cancer Center at University of Minnesota
🇺🇸Minneapolis, Minnesota, United States