Stem Cell Transplantation for Hematological Malignancies

Study Overview
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Brief Summary
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This protocol using busulfan, cyclophosphamide and melphalan has been designed as conditioning therapy for patients receiving stem cell transplantation for acute leukemia or myelodysplastic syndrome (MDS). The hypothesis is that this new regimen will be well tolerated and will cure the patient.

Detailed Description
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Subjects will be admitted to the bone marrow transplant unit and put in isolation to reduce exposure to infectious agents. Prior to transplantation, they will receive BUSULFAN via the central venous line, four times a day for four days, CYCLOPHOSPHAMIDE via the central venous line once a day for two days, and MELPHALAN via the central venous line for one day. Busulfan, cyclophosphamide, and melphalan are given to destroy the subject's cancer. As well, these drugs will destroy their immune system to help ensure the new stem cells take and grow after transplantation. On the day of transplantation, umbilical cord blood from the donor will be transfused via venous line. These new cells will replace the subject's bone marrow. After transplantation, the subjects will receive Cyclosporin A and either MMF or MTX Isolation will be continued until adequate numbers of cells are present in the blood to fight infection. Subjects will be discharged from the hospital when medically ready. They will be expected to return for follow-up to the blood and marrow transplant clinic at specific dates as determined by physicians.

Official Title
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Busulfan, Cyclophosphamide, and Melphalan Followed by Allogeneic Hematopoietic Cell Transplantation in Patients With Hematological Malignancies

Conditions
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Leukemia, Lymphocytic, Acute, AML, MDS

Intervention / Treatment
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* Procedure: Stem Cell Transplant
* Drug: Busulfan
* Drug: Cyclophosphamide
* Drug: Melphalan
* Drug: G-CSF
* Drug: ATG


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients must have a diagnosis of acute lymphocytic leukemia (ALL), acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) and currently be in complete remission. Patients must be either: - <18 years of age who are at least 6 months after initial hematopoietic cell transplant (HCT), - 19-35 years of age and at least 18 months after initial HCT, or - <35 years of age and have received sufficient radiation treatment to be ineligible for total body irradiation (TBI) containing preparative therapy Adequate major organ function including: - Cardiac: ejection fraction > or = 45% - Renal: creatinine clearance > or = 40 mL/min - Hepatic: no clinical evidence of hepatic failure (e.g. coagulopathy, ascites) - Karnofsky performance status > or = 70% or Lansky score > or = 50% Women of child bearing age must be using adequate birth control and have a negative pregnancy test. Written informed consent. Exclusion Criteria: Eligible for TBI containing preparative regimen. Active uncontrolled infection within one week of HCT. Pregnant or lactating females.

Ages Eligible for Study
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Maximum Age: 35 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: Treatment Arm<br>Patients treated with therapy plan consisting of Busulfan every 6 hours on days -7 through -4, Cyclophosphamide 60 mg/kg/day IV x 2 days, Melphalan 140 mg/m on day -1, antithymocyte globulin (ATG), G-CSF (granulocyte colony-stimulating factor) and stem cell transplantation on day 0. | Procedure: Stem Cell Transplant<br>* Certain cancers can be treated by giving patients stem cells that come from someone else. This is called a stem-cell transplant. As part of the transplant process, patients receive high doses of chemotherapy and/or radiation to treat their underlying disease, such as cancer. As one of its effects, this treatment also kills the healthy stem cells that are already in the marrow. The transplant provides new stem cells for the patient from a healthy donor; that replace the bone marrow and allow the blood counts to recover.<br>* Other names: hematopoietic stem cell transplant;Drug: Busulfan<br>* Prior to transplantation, subjects will receive BUSULFAN via the central venous line, four times a day for four days (days -7 through -4).<br>* Other names: Busulfex, Myleran;Drug: Cyclophosphamide<br>* Prior to stem cell transplantation, subjects will receive CYCLOPHOSPHAMIDE via the central venous line once a day for two days on days -3 and -2.<br>* Other names: Cytoxan, Neosar;Drug: Melphalan<br>* MELPHALAN will be given via the central venous line for one day, on day -1, prior to stem cell transplantation.<br>* Other names: Alkeran;Drug: G-CSF<br>* G-CSF is to be given daily IV beginning on day +1 until ANC 2.5 x 109/L.<br>* Other names: granulocyte colony-stimulating factor, Filgrastim, Neupogen;Drug: ATG<br>* ATG will be administered to umbilical cord blood recipients.<br>* Other names: antithymocyte globulin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Probability of Long-term Disease-free Survival (DFS) | Number of participants with long-term disease free survival after being treated with busulfan (BU), cyclophosphamide (CY) and melphalan (L-PAM) followed by HCT for hematological malignancies. | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Probability of Engraftment | Number of participants with engraftment after being treated with busulfan (BU), cyclophosphamide (CY) and melphalan (L-PAM) followed by HCT for hematological malignancies.. | 1 year | 
| Incidence of Acute Graft-versus-host Disease (GVHD) | Number of participants with acute GVHD after being treated with busulfan (BU), cyclophosphamide (CY) and melphalan (L-PAM) followed by HCT for hematological malignancies. | 100 days post-transplant | 
| Incidence Chronic Graft-versus-host Disease (GVHD) | Number of participants with chronic GVHD after being treated with busulfan (BU), cyclophosphamide (CY) and melphalan (L-PAM) followed by HCT for hematological malignancies. | 1 year | 
| Incidence of Regimen-related Toxicity 100 Days Post Transplant | Number of participants with regimen-related toxicity 100 days post transplant after being treated with busulfan (BU), cyclophosphamide (CY) and melphalan (L-PAM) followed by HCT for hematological malignancies. | 100 days post-transplant | 
| Incidence of Relapse | Number of patients with relapse after being treated with busulfan (BU), cyclophosphamide (CY) and melphalan (L-PAM) followed by HCT for hematological malignancies. | 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Stem Cell transplant, retransplant, hematological malignancies