Stem Cell Transplantation for Hematological Malignancies

Phase 2

Terminated

Conditions: Leukemia, Lymphocytic, Acute
AML
MDS

Interventions: Procedure: Stem Cell Transplant
Drug: Busulfan
Drug: Cyclophosphamide
Drug: Melphalan
Drug: G-CSF
Drug: ATG

Registration Number: NCT00176839

Lead Sponsor: Masonic Cancer Center, University of Minnesota

Brief Summary: 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: 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.

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 11

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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Treatment Arm	Stem Cell Transplant	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.
Treatment Arm	ATG	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.
Treatment Arm	Busulfan	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.
Treatment Arm	Melphalan	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.
Treatment Arm	Cyclophosphamide	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.
Treatment Arm	G-CSF	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.

Primary Outcome Measures

Name	Time	Method
Probability of Long-term Disease-free Survival (DFS)	1 year	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.

Secondary Outcome Measures

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