Stem Cell Transplant for Hematological Malignancy

University of Minnesota (UMN)

Status: Terminated

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

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

Study type: Interventional

Funder types: Other

Identifiers

NCT00176930

0107M05202 (Other Identifier)

2001LS049

MT2001-02 (Other Identifier)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 330 patients

Sex: All

Ages: Under 55 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

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330 participants in 8 patient groups

PBSC: No TBI

Experimental group

Description:

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

Treatment:

Biological: Stem Cell Transplant

Drug: Busulfan

Drug: Cyclophosphamide

Marrow : No TBI

Experimental group

Description:

Patients who are not able to receive Total Body Irradiation (TBI) receives cyclophosphamide, Busulfan and Bone Marrow as a source of stem cell transplant

Treatment:

Biological: Stem Cell Transplant

Drug: Busulfan

Drug: Cyclophosphamide

UCB : No TBI

Experimental group

Description:

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

Treatment:

Biological: Stem Cell Transplant

Drug: Busulfan

Drug: Cyclophosphamide

UCB : No TBI/Bu/Cy/ATG

Experimental group

Description:

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

Treatment:

Biological: Stem Cell Transplant

Drug: Busulfan

Drug: Equine ATG (ATGAM)

Drug: Cyclophosphamide

PBSC

Experimental group

Description:

Patients receiving cyclophosphamide, Total Body Irradiation (TBI) and Peripheral blood stem cells as a source of transplant

Treatment:

Biological: Stem Cell Transplant

Radiation: Total Body Irradiation

Drug: Cyclophosphamide

Marrow

Experimental group

Description:

Patients receiving cyclophosphamide, Total Body Irradiation (TBI) and Bone Marrow as a source of stem cell transplant

Treatment:

Biological: Stem Cell Transplant

Radiation: Total Body Irradiation

Drug: Cyclophosphamide

UCB

Experimental group

Description:

Patients receiving cyclophosphamide, Total Body Irradiation (TBI), and Umbilical Cord Blood (UCB) as a source of stem cell transplant

Treatment:

Biological: Stem Cell Transplant

Radiation: Total Body Irradiation

Drug: Cyclophosphamide

Co-Enroll From MT0403

Experimental group

Description:

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)

Treatment:

Biological: Stem Cell Transplant

Radiation: Total Body Irradiation

Drug: Cyclophosphamide

Biological: CD4+/CD25+ cells