Umbilical Cord Blood T-Regulatory Cell Infusion Followed by Donor Umbilical Cord Blood Transplant in Treating Patients With High-Risk Leukemia or Other Hematologic Diseases

Summary

RATIONALE: Giving chemotherapy, such as fludarabine and cyclophosphamide, and total-body irradiation before a donor umbilical cord blood stem cell transplant helps stop the growth of cancer or abnormal cells and prepares the patient's bone marrow for the stem cells. When the healthy stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. The donated stem cells may replace the patient's immune cells and help destroy any remaining cancer or abnormal cells (graft-versus-tumor effect). Giving an infusion of the donor's T-regulatory cells before the transplant may help increase this effect. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells. Giving cyclosporine and mycophenolate mofetil after the transplant may stop this from happening.

PURPOSE: This phase I trial is studying the side effects and best dose of umbilical cord blood T-regulatory cell infusion followed by donor umbilical cord blood transplant in treating patients with high-risk leukemia or other hematologic diseases.

Conditions

• Graft Versus Host Disease
• Leukemia
• Lymphoma
• Multiple Myeloma and Plasma Cell Neoplasm
• Myelodysplastic Syndromes
• Secondary Myelofibrosis

Interventions

DRUG

cyclophosphamide

Cyclophosphamide 60 mg/kg/day will be administered as a 2 hour intravenous infusion with a high volume fluid flush and mesna (MT(S)9006) on day -8 and -7 one hour after fludarabine infusion.

DRUG

cyclosporine

Will be administered beginning on day -3 and adjusted to maintain a level of \>200. For adults the initial dose will be 2.5 mg/kg intravenously (IV) over 2 hours every 12 hours.

DRUG

fludarabine phosphate

Fludarabine 25 mg/m\^2/day will be administered as a 1 hour intravenous infusion on days -9 through -7.

DRUG

mycophenolate mofetil

All patients will begin mycophenolate mofetil (MMF) on day -3, at the dose of 3 grams/day divided into 2 or 3 doses (every 12 or 8 hours).

PROCEDURE

Treg cell infusion

On day -1 prior to UCB transplantation, Treg cells will be infused IV without in-line filtration. A semi-log dose escalation of CD4+CD25+ Treg cells is scheduled with 3 patients at each step. Doses will be 0.1 x 10\^6/kg, 0.3 x 10\^6/kg, 1 x 10\^6/kg and 3 x 10\^6/kg weight (determined on the day prior to administration of the preparative therapy).

PROCEDURE

umbilical cord blood transplantation

Following the administration of the preparative therapy, all subjects will undergo UCB transplantation. The UCB will be administrated by IV infusion without in-line filtration.

RADIATION

total-body irradiation

Radiotherapy: 165 cGy will be administered on day -5 through -2 two fractions each day.

Sponsors & Collaborators

• Masonic Cancer Center, University of Minnesota

  lead OTHER

Principal Investigators

• Claudio G. Brunstein, MD, PhD · Masonic Cancer Center, University of Minnesota

Study Design

Allocation

NA

Purpose

TREATMENT

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Min Age

18 Years

Max Age

45 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2007-05-31

Primary Completion

2008-03-31

Completion

2008-03-31

Countries

• United States

Study Locations