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REDUCED INTENSITY CONDITIONING (RIC):

Flu/Cy/TBI: Patients receive cyclophosphamide IV over 2 hours on day -6 and fludarabine phosphate IV on days -6 to -2 and undergo total-body irradiation on day -1.

Flu/Mel: Patients receive fludarabine daily on days -5 to -2, a single dose of melphalan on day -2, and ATG on day -3 and day-2.

GVHD PROPHYLAXIS: Patients receive cyclosporine PO or IV over 2 hours every 12 hours on beginning on days -5 to 100 with taper beginning on day 100 and mycophenolate mofetil IV or PO BID on days -5 to 100.

TRANSPLANT: Patients undergo a co-transplantation of an intra-osseous umbilical cord blood transplantation and a mesenchymal stem cell transplantation on day 0.

All patients will receive a single IV dose of 50 mg/kg of cyclophosphamide on day -6

cyclophosphamide

Given by IV during prep at 40mg/m2 for 5 days

fludarabine phosphate

Undergo single fraction of reduced intensity conditioning (RIC) regimen of 200 cGy TBI without shielding on day -1

total-body irradiation

Initiated in patients on the day -5. Cyclosporine will be administered orally or intravenously at 2 mg/kg/dose every 12 hours for 2-hour period. Cyclosporine will continue until day +100

cyclosporine

Given at 1g intravenously or orally twice daily from day -5 to +100, or as clinically indicated.

mycophenolate mofetil

Following RIC, on day T+0, dimethylsulphoxide will be removed from the cord blood cells and given as transplant.

umbilical cord blood transplantation

The total dosage of hMSC will be 2x10\^6cells/kg (+/-20%).

mesenchymal stem cell transplantation

Leland Metheny, MD

This clinical trial studies intra-osseous donor umbilical cord blood and mesenchymal stromal cell co-transplant in treating patients with hematologic malignancies. Giving low doses of chemotherapy and total-body irradiation before a co-transplant of donor umbilical cord blood and mesenchymal stromal cells into the bone (intra-osseous) helps stop the growth of cancer cells. It may also stop the patient's immune system from rejecting the donor's stem cells. The donated stem cells may replace the patient's immune cells and help destroy any remaining cancer cells (graft-versus-tumor effect). Sometimes the transplanted cells from a donor can also make an immune response against the body's normal cells. Giving cyclosporine and mycophenolate mofetil at the time of transplant may stop this from happening.

PRIMARY OBJECTIVES:

I. To estimate the feasibility of combining intra-osseous umbilical cord blood (UCB) hematopoietic stem cells and human mesenchymal stromal cells (hMSC) following reduced intensity conditioning (RIC).

SECONDARY OBJECTIVES:

I. To estimate the time to engraftment of intra-osseous (IO) UCB transplant combined with hMSC following RIC.

II. To estimate the safety profile of IO UBC transplant combined with hMSC.

OUTLINE:

REDUCED INTENSITY CONDITIONING: Patients receive cyclophosphamide intravenously (IV) over 2 hours on day -6 and fludarabine phosphate IV on days -6 to -2 and undergo total body irradiation (TBI) on day -1.

GRAFT-VERSUS-HOST DISEASE (GVHD) PROPHYLAXIS: Patients receive cyclosporine orally (PO) or IV over 2 hours every 12 hours on beginning on days -5 to 100 with taper beginning on day 100 and mycophenolate mofetil IV or PO twice daily (BID) on days -5 to 100.

TRANSPLANT: Patients undergo intra-osseous UCB and hMSC co-transplant on day 0.

After completion of study treatment, patients are followed up at days 28 and 100, and then at 6, 9, and 12 months.

Intra-Osseous Co-Transplant of UCB and hMSC

Intra-osseous Co-transplant of Cord Blood and Mesenchymal Stromal Cells: A Feasibility Study

Primary graft failure is defined by \<10% BM cellularity in bone marrow biopsies. Failure in more than 30% of patients will indicate unfeasibility of treatment

Primary graft failure is defined by \<500 ANC cell/ul in bone marrow biopsies. Failure in more than 30% of patients will indicate unfeasibility of treatment

Primary graft failure is defined by hematopoietic recovery with \<10% donor cell chimerism. Failure in more than 30% of patients will indicate unfeasibility of treatment

Primary graft failure is defined by hematopoietic recovery with \<40% donor cell chimerism. Failure in more than 30% of patients will indicate unfeasibility of treatment

The rate of neutrophil recovery and median time of recovery will be estimated using the methods of Kaplan and Meier.

The rate of platelet recovery and median time of recovery will be estimated using the methods of Kaplan and Meier.

The median time of neutrophil recovery will be estimated using the methods of Kaplan and Meier.

The median time of platelet recovery will be estimated using the methods of Kaplan and Meier.

National Cancer Institute (NCI)

Case Comprehensive Cancer Center

Principal Investigator

Spots Global Cancer Trial Database for human mesenchymal stromal cells