Stem Cell Transplant for Hematological Malignancy

Not Applicable

Terminated

Conditions: Leukemia, Lymphocytic, Chronic
JMML
Leukemia, Myeloid, Chronic
AML
MDS
Non-hodgkin's Lymphoma
Leukemia, Lymphocytic, Acute
Multiple Myeloma
Hodgkin's Disease

Interventions: Biological: Stem Cell Transplant
Drug: Cyclophosphamide
Radiation: Total Body Irradiation
Drug: Busulfan
Biological: CD4+/CD25+ cells
Drug: Equine ATG (ATGAM)

Registration Number: NCT00176930

Lead Sponsor: Masonic Cancer Center, University of Minnesota

Brief Summary: The purpose of this study is to develop a standard of care treatment using allogeneic stem cells for patients with cancers of the blood.

The protocol was revised to reflect that this study is considered "treatment guidelines", rather than a research study.

Detailed Description: Preparative regimen using total body irradiation (TBI) and cyclophosphamide:

1. on day -6 and -5: cyclophosphamide is given,

2. on day -4, -3, -2, and -1: TBI is given,

3. on day 0: stem cell or bone marrow is infused.

Alternate preparative therapy for patients not able to receive TBI

The chemotherapy (cyclophosphamide and busulfan) is given with the intent of destroying the bone marrow, eliminating any cancerous and preparing for the transplant of the donor's blood stem cells by suppressing the immune system.

l. Ten days before the transplant (Day 10), subjects will be admitted to the bone marrow transplant unit and placed in isolation to reduce exposure to infections. Isolation will be continued until adequate numbers of cells are present in the blood to fight infection.

2. On day -9, -8, -7, -6 busulfan is given.

3. On day -5, -4, -3, -2 cyclophosphamide is given.

4. On day -1 no therapy is given (day of rest).

5. On day 0 the donor stem cells are given intravenously. Additional cells may be given on day +1 or 2 as needed.

Transplant:

Subjects will be admitted to the bone marrow transplant unit and put in isolation to reduce exposure to infectious agents. During this time, they will receive the preparative treatment outlined above. Once they have received the preparative regimen, stem cells will be obtained from the donor and given intravenously.

The new stem cells will replace the bone marrow that was damaged by the treatment for the cancer.

Isolation will be continued until adequate numbers of cells are present in the blood to fight infection. Subjects will then be transferred from the bone marrow transplant unit and discharged from the hospital when medically ready. Subjects will be expected to return for follow-up to the bone marrow transplant clinic at specific dates as determined by their physician.

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 330

Inclusion Criteria

Donor will be <75 years of age and in good health.
Recipients will be < or = 55 years, will have normal organ function (excluding bone marrow) and will have a Karnofsky activity assessment > or = 90%.
Recipients with related or unrelated donor matched at the HLA A, B, DRB1 loci, or mismatched related or unrelated (if < 35 years old) at a single HLA A, B, DRB1 locus.
Recipients will be eligible in one of the following disease categories
Chronic myelogenous leukemia in accelerated phase or in post blast crisis second or greater chronic phase; or in chronic phase but intolerant of or resistant to tyrosine kinase inhibitors.
Acute myelocytic leukemia in first or greater remission, or first, second or third relapse.
Acute lymphocytic leukemia in the 2nd or greater bone marrow remission.
High risk children will be transplanted in first remission if they meet criteria
Myelodysplastic syndrome.
Myeloproliferative Diseases - (i.e. myelofibrosis, chronic myelomonocytic leukemia (CMML))
Juvenile myelomonocytic leukemia
Chronic lymphocytic leukemia
Advanced non-Hodgkin's (NHL).
Advanced Hodgkin's disease beyond PR2 (> CR3, > PR3).
Multiple Myeloma after initial therapy.
Donors and recipients signed informed consent

Exclusion Criteria

donors and recipients should meet the following test criteria.

required for donors:
- anti-HIV, Hepatitis B, surface antigen, anti-HCV, CMV, HSV, EBV serologies, pre-priming.
- CBC, platelet count each day of apheresis, day 0 (or 1 or 2 as needed)
required for recipients:
- anti-HIV, Hepatitis B, surface antigen, anti-HCV, CMV, HSV, EBV serologies, pre-transplant.

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Co-Enroll From MT0403	CD4+/CD25+ cells	Patients receiving cyclophosphamide, Total Body Irradiation (TBI) , CD4+CD25+ and Peripheral Blood Stem Cells (PBSC) as a source of transplant. These patients are co-enrolled on the MT2004-03 trial (NCT00725062)
PBSC: No TBI	Stem Cell Transplant	Patients who are not able to receive Total Body Irradiation (TBI) receives cyclophosphamide, Busulfan and Peripheral Blood Stem Cells (PBSC) as a source of transplant
Marrow : No TBI	Stem Cell Transplant	Patients who are not able to receive Total Body Irradiation (TBI) receives cyclophosphamide, Busulfan and Bone Marrow as a source of stem cell transplant
UCB : No TBI	Stem Cell Transplant	Patients who are not able to receive Total Body Irradiation (TBI) receives cyclophosphamide, Busulfan and Umbilical Cord Blood (UCB) as a source of stem cell transplant
UCB : No TBI/Bu/Cy/ATG	Equine ATG (ATGAM)	Patients who receives Umbilical Cord Blood (UCB) as a source of transplant and who have not had chemotherapy in the prior 3 months receives ATG in addition to cyclophosphamide, Busulfan preparative regimen
PBSC	Stem Cell Transplant	Patients receiving cyclophosphamide, Total Body Irradiation (TBI) and Peripheral blood stem cells as a source of transplant
PBSC	Total Body Irradiation	Patients receiving cyclophosphamide, Total Body Irradiation (TBI) and Peripheral blood stem cells as a source of transplant
UCB : No TBI/Bu/Cy/ATG	Stem Cell Transplant	Patients who receives Umbilical Cord Blood (UCB) as a source of transplant and who have not had chemotherapy in the prior 3 months receives ATG in addition to cyclophosphamide, Busulfan preparative regimen
Marrow	Stem Cell Transplant	Patients receiving cyclophosphamide, Total Body Irradiation (TBI) and Bone Marrow as a source of stem cell transplant
Marrow	Total Body Irradiation	Patients receiving cyclophosphamide, Total Body Irradiation (TBI) and Bone Marrow as a source of stem cell transplant
UCB	Stem Cell Transplant	Patients receiving cyclophosphamide, Total Body Irradiation (TBI), and Umbilical Cord Blood (UCB) as a source of stem cell transplant
UCB	Total Body Irradiation	Patients receiving cyclophosphamide, Total Body Irradiation (TBI), and Umbilical Cord Blood (UCB) as a source of stem cell transplant
Co-Enroll From MT0403	Stem Cell Transplant	Patients receiving cyclophosphamide, Total Body Irradiation (TBI) , CD4+CD25+ and Peripheral Blood Stem Cells (PBSC) as a source of transplant. These patients are co-enrolled on the MT2004-03 trial (NCT00725062)
Co-Enroll From MT0403	Total Body Irradiation	Patients receiving cyclophosphamide, Total Body Irradiation (TBI) , CD4+CD25+ and Peripheral Blood Stem Cells (PBSC) as a source of transplant. These patients are co-enrolled on the MT2004-03 trial (NCT00725062)
PBSC: No TBI	Busulfan	Patients who are not able to receive Total Body Irradiation (TBI) receives cyclophosphamide, Busulfan and Peripheral Blood Stem Cells (PBSC) as a source of transplant
PBSC: No TBI	Cyclophosphamide	Patients who are not able to receive Total Body Irradiation (TBI) receives cyclophosphamide, Busulfan and Peripheral Blood Stem Cells (PBSC) as a source of transplant
Marrow : No TBI	Cyclophosphamide	Patients who are not able to receive Total Body Irradiation (TBI) receives cyclophosphamide, Busulfan and Bone Marrow as a source of stem cell transplant
UCB : No TBI	Cyclophosphamide	Patients who are not able to receive Total Body Irradiation (TBI) receives cyclophosphamide, Busulfan and Umbilical Cord Blood (UCB) as a source of stem cell transplant
Marrow : No TBI	Busulfan	Patients who are not able to receive Total Body Irradiation (TBI) receives cyclophosphamide, Busulfan and Bone Marrow as a source of stem cell transplant
UCB : No TBI	Busulfan	Patients who are not able to receive Total Body Irradiation (TBI) receives cyclophosphamide, Busulfan and Umbilical Cord Blood (UCB) as a source of stem cell transplant
UCB : No TBI/Bu/Cy/ATG	Cyclophosphamide	Patients who receives Umbilical Cord Blood (UCB) as a source of transplant and who have not had chemotherapy in the prior 3 months receives ATG in addition to cyclophosphamide, Busulfan preparative regimen
UCB : No TBI/Bu/Cy/ATG	Busulfan	Patients who receives Umbilical Cord Blood (UCB) as a source of transplant and who have not had chemotherapy in the prior 3 months receives ATG in addition to cyclophosphamide, Busulfan preparative regimen
PBSC	Cyclophosphamide	Patients receiving cyclophosphamide, Total Body Irradiation (TBI) and Peripheral blood stem cells as a source of transplant
Marrow	Cyclophosphamide	Patients receiving cyclophosphamide, Total Body Irradiation (TBI) and Bone Marrow as a source of stem cell transplant
UCB	Cyclophosphamide	Patients receiving cyclophosphamide, Total Body Irradiation (TBI), and Umbilical Cord Blood (UCB) as a source of stem cell transplant
Co-Enroll From MT0403	Cyclophosphamide	Patients receiving cyclophosphamide, Total Body Irradiation (TBI) , CD4+CD25+ and Peripheral Blood Stem Cells (PBSC) as a source of transplant. These patients are co-enrolled on the MT2004-03 trial (NCT00725062)

Primary Outcome Measures

Name	Time	Method
Number of Participants Experiencing Disease-Free Survival at 2 Years Post Transplant	2 years	Disease-Free Survival is the length of time during and after medication or treatment during which the disease being treated (usually cancer) does not get worse. It is sometimes used as a metric to study the health of a person with a disease to try to determine how well a new treatment is working.
Number of Participants Experiencing Disease-Free Survival at 5 Years Post Transplant	5 years	Disease-Free Survival is the length of time during and after medication or treatment during which the disease being treated (usually cancer) does not get worse. It is sometimes used as a metric to study the health of a person with a disease to try to determine how well a new treatment is working.

Secondary Outcome Measures

Name	Time	Method
Number of Participants With Persistence or Relapse of Malignancy at 2 Years Post Transplant	2 years	Defined as the return of disease after its apparent recovery/cessation. Patients with leukemia and lymphoma involving the BM and multiple myeloma will have this done by BM biopsy and additional special studies such as cytogenetics or flow cytometry as appropriate. Patients with lymphoma and myeloma will 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 Participants With Persistence or Relapse of Malignancy at 5 Years Post Transplant	5 years	Defined as the return of disease after its apparent recovery/cessation. Patients with leukemia and lymphoma involving the BM and multiple myeloma will have this done by BM biopsy and additional special studies such as cytogenetics or flow cytometry as appropriate. Patients with lymphoma and myeloma will 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 Participants Who Were Alive at 2 Year Post Transplant	2 years	The percentage of people in a study or treatment group who are alive for a certain period of time after they were diagnosed with or treated for a disease, such as cancer.
Number of Participants Who Were Alive at 5 Year Post Transplant	5 years	The percentage of people in a study or treatment group who are alive for a certain period of time after they were diagnosed with or treated for a disease, such as cancer.
Number 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. Determine the incidence of chronic GVHD 1 year post transplant. Patients will be staged weekly between days 0 and 100 after transplantation using standard criteria. Patients will be assigned an overall GVHD score based on extent of skin rash, volume of diarrhea and maximum bilirubin level.
Number of Participants With Neutrophil Engraftment	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.
Number of Participants With Acute Graft-versus-host Disease (GVHD)	Day 100	Acute Graft-Versus-Host Disease (aGVHD) is a severe short-term complication created by infusion of donor cells into a foreign host. Determine the incidence of grade II-IV acute graft-versus-host disease (GVHD) at day 100 post transplant. 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.
Number of Participants Experiencing 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.