Busulfan, Melphalan, and Fludarabine With Peri-transplant Palifermin, Followed by a T-Cell Depleted Hematopoietic Stem Cell Transplant From HLA Matched or Mismatched Related or Unrelated Donors in Patients With Advanced Myelodysplastic Syndromes (MDS) and Acute Myeloid Leukemia (AML)

Study Overview
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Brief Summary
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This study will see if the researchers can lower that risk by giving the patient Palifermin. This drug helps protect the lining of the mouth, throat, and stomach. These areas typically get sores or ulcers while the blood cell counts are very low. The patient can get infections in or from these sores. Palifermin might also help the immune system recover faster. It is currently approved for patients who receive their own stem cells. That is called an autologous transplant. This study will test the use of Palifermin for T-cell depleted allogeneic stem cell transplants.

Official Title
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A Phase II Trial of Busulfan, Melphalan, and Fludarabine With Peri-transplant Palifermin, Followed by a T-Cell Depleted Hematopoietic Stem Cell Transplant From HLA Matched or Mismatched Related or Unrelated Donors in Patients With Advanced Myelodysplastic Syndromes (MDS) and Acute Myeloid Leukemia (AML)

Conditions
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Acute Myeloid Leukemia, Advanced Myelodysplastic Syndromes

Intervention / Treatment
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* Drug: Busulfan, Melphalan, Fludarabine, Anti-Thymocyte Globulin, Palifermin, Stem cell transplant


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients should be < 65 years. Patients > or equal to 65 years will be accrued on a case by case basis after discussion and approval by the BMT Service. Patients may be of either gender or any ethnic background. Patients must have a Karnofsky or Lansky Performance Status > or equal to 70%. Patients must have adequate organ function measured by: * Cardiac: asymptomatic or if symptomatic then LVEF at rest must be > or equal to 50% and must improve with exercise. Hepatic: < 3x ULN ALT and < 1.5 total serum bilirubin, unless there is congenital benign hyperbilirubinemia. Renal: serum creatinine < than or equal to 1.2 mg/dl or if serum creatinine is outside the normal range, then CrCl > 60-ml/min/1.73 m2 Pulmonary: asymptomatic or if symptomatic, DLCO > 50% of predicted (corrected for hemoglobin) Each patient must be willing to participate as a research subject and must sign an informed consent form. Parent or legal guardians of patients who are minors will sign the informed consent form. Exclusion Criteria: Active CNS or skin leukemic involvement Female patients who are pregnant or breast-feeding Active viral, bacterial or fungal infection Patient seropositive for HIV-I/II; HTLV -I/II Patients who have undergone a prior allogeneic or autologous stem cell transplant within the previous six months. Patients who have had a previous malignancy that is not in remission.

Ages Eligible for Study
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Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>This is a single arm phase II trial to assess the efficacy (decrease the transplant related mortality) and safety of peri-transplant Palifermin in combination with a preparative regimen with busulfan, melphalan, fludarabine, and anti-thymocyte globulin (ATG), and a T cell depleted stem cell transplant from a histocompatible related or unrelated donor in patients with advanced MDS and AML evolved from MDS. The addition of Palifermin is to decrease the toxicity and the infection rate associated with this regimen and transplant type and to foster earlier immune reconstitution. | Drug: Busulfan, Melphalan, Fludarabine, Anti-Thymocyte Globulin, Palifermin, Stem cell transplant<br>* Patients will receive Palifermin 60 mcg/kg/day IV on three consecutive days with the last dose administered no less than 24 and no more than 48 hr prior to start of cytoreduction. The preparative regimen to be used for transplants will consist: of busulfan administered in 12 doses over three days of 0.8 mg/kg IV for patients > or = to 4 years of age or 1.0 mg/kg IV for patients < 4 years of age; melphalan 70 mg/m2 IV x 2 days; and, fludarabine 25 mg/m2 IV x 5 days<br>* Other names: guidelines.;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To Reduce the Early Transplant-related Mortality. |  | conclusion of study | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To Improve the Quality of Immune Reconstitution Following Transplantation. |  | conclusion of study | 
| To Reduce the Incidence Rate of Fatal Post Transplant Infectious Complications. |  | conclusion of study | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Busulfan, Melphalan, Fludarabine, 08-008