Cord Blood Fucosylation to Enhance Homing and Engraftment in Patients With Hematologic Malignancies

Summary

The goal of this clinical research study is to learn if it is safe and feasible to transplant changed cord blood for patients with leukemia or lymphoma. Researchers also want to learn if this can help to control the disease.

The cord blood will be changed to make use of sugar that is found in small amounts in blood cells. It plays a role in signaling where in the body the transplanted cells should go to. Adding more sugars to the cord blood cells in the laboratory is designed to help the cord blood cells find their way faster to the bone marrow. This may help your blood counts to recover faster. This process is called fucosylation.

Anti-thymocyte globulin (ATG) is a protein that removes immune cells that cause damage to the body.

Clofarabine is designed to interfere with the growth and development of cancer cells.

Fludarabine is designed to interfere with the DNA (genetic material) of cancer cells, which may cause the cancer cells to die. This chemotherapy is also designed to block your body's ability to reject the donor's bone marrow cells.

Melphalan and busulfan are designed to bind to the DNA of cells, which may cause cancer cells to die.

Mycophenolate mofetil (MMF) and tacrolimus are designed to block the donor cells from growing and spreading in a way that could cause graft versus host disease (GVHD -- a condition in which transplanted tissue attacks the recipient's body). This may help to prevent GVHD.

Rituximab is designed to attach to cancer cells, which may cause them to die.

Conditions

• Blood And Marrow Transplantation
• Leukemia
• Lymphoma
• Transplantation Infection
• Transplantation, Bone Marrow

Interventions

DRUG

Melphalan

140 mg/m2 by vein on Day -2 only for Fludarabine + Melphalan group.

DRUG

Fludarabine

10 mg/m2 by vein on Days -7 to -4 for Melphalan + Thiotepa + Fludarabine group, or 40 mg on Days -5 to -2 for Fludarabine + Melphalan group.

DRUG

Mycophenolate mofetil

15 mg/kg (actual body weight with a maximum dose of 1 gram twice daily) by vein or by mouth twice a day from Days -3 to +100 in the absence of Graft vs Host Disease (GvHD).

DRUG

Tacrolimus

Starting dose 0.03 mg/kg or 0.015 mg/kg (ideal body weight) by vein starting on Day -2 and tapered around Day +180 if no Graft vs Host Disease (GvHD) is present.

PROCEDURE

Cord Blood Infusion

Cord blood infusion on Day 0. Each participant will receive cells from one unexpanded cord blood sample plus cells from a second cord blood sample that has undergone fucosylation.

DRUG

Rituximab

375 mg/m\^2 by vein on Day -10 for B cell malignancy.

DRUG

ATG

1.25 mg/Kg by vein on Day -4. 1.75 mg/Kg by vein on Day -3.

DRUG

Busulfan

Busulfan per standard of care, test dose either as an outpatient prior to admission or as an inpatient on Day -9. Busulfan pharmacokinetics performed with test dose and the first dose on Day -7 per standard of care. Doses of Days -5 and -4 subsequently adjusted to target an AUC of 4,000 microMol.min-1.

DRUG

Clofarabine

30 mg/m\^2 IV Day -7 to Day -4;

RADIATION

Total Body Irradiation (TBI)

2 Gy in AM of Day -3.

Sponsors & Collaborators

• American Stem Cell, Inc.

  collaborator OTHER

• National Cancer Institute (NCI)

  collaborator NIH

• M.D. Anderson Cancer Center

  lead OTHER

Principal Investigators

• Elizabeth Shpall, MD · M.D. Anderson Cancer Center

Study Design

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Min Age

1 Year

Max Age

80 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2012-07-13

Primary Completion

2017-04-25

Completion

2017-04-25

FDA Drug

Yes

Countries

• United States

Study Locations