Busulfan and Cyclophosphamide Followed By ALLO BMT

Not Applicable

Terminated

Conditions: Myelodysplastic Syndrome
Acute Lymphoblastic Leukemia
Acute Myeloid Leukemia

Interventions: Drug: Allopurinol
Drug: Keppra
Drug: Busulfan
Drug: Cyclophosphamide
Drug: Tacrolimus
Drug: Mycophenolate mofetil
Biological: Allogeneic hematopoietic stem cell transplant
Biological: Filgrastim
Biological: antithymocyte globulin

Registration Number: NCT01685411

Lead Sponsor: Masonic Cancer Center, University of Minnesota

Brief Summary: This is a treatment guideline to allow routine clinical data to be collected and maintained in Oncore (clinical database) and the University of Minnesota Blood and Marrow Database as part of the historical database maintained by the department.

Detailed Description: This is a single arm trial to evaluate the efficacy of busulfan and cyclophosphamide followed by an allogeneic hematopoietic stem cell transplant (HSCT) in the treatment of hematological malignancies. The intent of this study is to provide a protocol that will use unmanipulated allogeneic hematopoietic stem cells from related and unrelated donors after a common preparative regimen.

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 5

Inclusion Criteria

Diagnosis of acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) and current in complete remission meeting one of the following:
- <45 years of age who are at least 6 months after initial hematopoietic stem cell transplant (HSCT)
- <45 years of age and have received sufficient radiation treatment to be ineligible for total body irradiation (TBI) containing preparative therapy
Karnofsky performance status >70% or if <16 years of age, a Lansky play score >50
Adequate major organ function including:
- cardiac: left ventricular ejection fraction >45% by echocardiogram (ECHO/MUGA)
- renal: creatinine clearance >40 mL/min/1.73m^2
- hepatic: no clinical evidence of hepatic failure (e.g., coagulopathy, ascites)
An acceptable source of stem cells according to current University of Minnesota Bone Marrow Transplant program guidelines. Acceptable stem cell sources include:
- HLA-matched related or unrelated donor bone marrow (6/6 or 5/6 antigen match)
- HLA-matched related or unrelated donor peripheral blood stem cells
- related or single or double unrelated donor umbilical cord blood (6/6, 5/6 or 4/6 match)
Women of childbearing age must have a negative pregnancy test and all sexually active participants must agree to use effective contraception during study treatment
Written consent (adult or parent/guardian)

Exclusion Criteria

eligible for TBI containing preparative regimen
active uncontrolled infection within one week of study enrollment
pregnant or lactating female

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Allogeneic Hematopoietic Stem Cell Transplant	Allogeneic hematopoietic stem cell transplant	Patients treated with Allopurinol, Keppra, Busulfan, Cyclophosphamide, Filgrastim, antithymocyte globulin, Tacrolimus, Mycophenolate mofetil and allogeneic hematopoietic stem cell transplant infusion.
Allogeneic Hematopoietic Stem Cell Transplant	Filgrastim	Patients treated with Allopurinol, Keppra, Busulfan, Cyclophosphamide, Filgrastim, antithymocyte globulin, Tacrolimus, Mycophenolate mofetil and allogeneic hematopoietic stem cell transplant infusion.
Allogeneic Hematopoietic Stem Cell Transplant	antithymocyte globulin	Patients treated with Allopurinol, Keppra, Busulfan, Cyclophosphamide, Filgrastim, antithymocyte globulin, Tacrolimus, Mycophenolate mofetil and allogeneic hematopoietic stem cell transplant infusion.
Allogeneic Hematopoietic Stem Cell Transplant	Keppra	Patients treated with Allopurinol, Keppra, Busulfan, Cyclophosphamide, Filgrastim, antithymocyte globulin, Tacrolimus, Mycophenolate mofetil and allogeneic hematopoietic stem cell transplant infusion.
Allogeneic Hematopoietic Stem Cell Transplant	Allopurinol	Patients treated with Allopurinol, Keppra, Busulfan, Cyclophosphamide, Filgrastim, antithymocyte globulin, Tacrolimus, Mycophenolate mofetil and allogeneic hematopoietic stem cell transplant infusion.
Allogeneic Hematopoietic Stem Cell Transplant	Busulfan	Patients treated with Allopurinol, Keppra, Busulfan, Cyclophosphamide, Filgrastim, antithymocyte globulin, Tacrolimus, Mycophenolate mofetil and allogeneic hematopoietic stem cell transplant infusion.
Allogeneic Hematopoietic Stem Cell Transplant	Cyclophosphamide	Patients treated with Allopurinol, Keppra, Busulfan, Cyclophosphamide, Filgrastim, antithymocyte globulin, Tacrolimus, Mycophenolate mofetil and allogeneic hematopoietic stem cell transplant infusion.
Allogeneic Hematopoietic Stem Cell Transplant	Tacrolimus	Patients treated with Allopurinol, Keppra, Busulfan, Cyclophosphamide, Filgrastim, antithymocyte globulin, Tacrolimus, Mycophenolate mofetil and allogeneic hematopoietic stem cell transplant infusion.
Allogeneic Hematopoietic Stem Cell Transplant	Mycophenolate mofetil	Patients treated with Allopurinol, Keppra, Busulfan, Cyclophosphamide, Filgrastim, antithymocyte globulin, Tacrolimus, Mycophenolate mofetil and allogeneic hematopoietic stem cell transplant infusion.

Primary Outcome Measures

Name	Time	Method
Counts of Participants With Disease Free Survival	2 Years	The length of time after treatment ends that a patient survives without any signs or symptoms of that cancer or any other type of cancer. In a clinical trial, measuring the disease-free survival is one way to see how well a new treatment works. Patients with leukemia involving the BM and myelodysplastic syndrome will have this assessed by BM biopsy and additional special studies such as cytogenetics or flow cytometry as appropriate. Patients will also have radiology studies such as plain X-rays or CT scans and/or other studies such as blood tumor markers to document presence or absence of disease as clinically indicated.
Count of Participants With Disease Free Survival	7 Years	The length of time after treatment ends that a patient survives without any signs or symptoms of that cancer or any other type of cancer. In a clinical trial, measuring the disease-free survival is one way to see how well a new treatment works. Patients with leukemia involving the BM and myelodysplastic syndrome will have this done by BM biopsy and additional special studies such as cytogenetics or flow cytometry as appropriate. Patients will also have radiology studies such as plain X-rays or CT scans and/or other studies such as blood tumor markers to document presence or absence of disease as clinically indicated.

Secondary Outcome Measures

Name	Time	Method
Percentage of Participants With Treatment-Related Toxicity	1 year	In the field of transplantation, toxicity is high and all deaths without previous relapse or progression are usually considered as related to transplantation.
Number of Participant Who Were Alive at 5 Years Post Transplant	5 Years	Overall survival will be defined as time from date of enrollment to date of death or censored at the date of last documented contact for patients still alive.
Percentage of Participants With Acute Graft-Versus-Host Disease by Grade	Day 100	Acute Graft-Versus-Host Disease is a severe short-term complication created by infusion of donor cells into a foreign host. Patients will be staged weekly between days 0 and 100 after transplantation using standard criteria used for staging. Patients will be assigned an overall GVHD score based on extent of skin rash, volume of diarrhea and maximum bilirubin level. The stages of individual organ involvement are combined to produce an overall grade. Grade I GVHD is characterized as mild disease, grade II GVHD as moderate, grade III as severe, and grade IV life-threatening.
Percentage of Participants With Engraftment Failure	Day 42	Graft failure is defined as not accepting donated cells. The donated cells do not make the new white blood cells, red blood cells and platelets.
Number of Participant Who Were Alive at 2 Years Post Transplant	2 Years	Overall survival will be defined as time from date of enrollment to date of death or censored at the date of last documented contact for patients still alive.
Count of Participants Who Achieved Neutrophil Engraftment	By Day 42	Neutrophil engraftment is defined as the first day of three consecutive days where the neutrophil count (absolute neutrophil count) is 500 cells/mm\^3 (0.5 x 10\^9/L) or greater.
Percentage of Participants With Chronic Graft-Versus-Host Disease	1 Year	Chronic Graft-Versus-Host Disease is a severe long-term complication created by infusion of donor cells into a foreign host. Patients will be staged weekly between days 0 and 100 after transplantation using standard criteria used for staging. Patients will be assigned an overall GVHD score based on extent of skin rash, volume of diarrhea and maximum bilirubin level. The stages of individual organ involvement are combined to produce an overall grade. Grade I GVHD is characterized as mild disease, grade II GVHD as moderate, grade III as severe, and grade IV life-threatening.
Percentage of Participants With Relapse	2 Years	The return of disease after its apparent recovery/cessation. Patients with leukemia involving the BM and myelodysplastic syndrome will have this assessed by BM biopsy and additional special studies such as cytogenetics or flow cytometry as appropriate. Patients will also have radiology studies such as plain X-rays or CT scans and/or other studies such as blood tumor markers to document presence or absence of disease as clinically indicated.
Number of Participant Who Were Alive at 7 Years Post Transplant	7 Years	Overall survival will be defined as time from date of enrollment to date of death or censored at the date of last documented contact for patients still alive.