Allogeneic Hematopoietic Cell Transplantation for Patients With Busulfex-based Regimen

Summary

RATIONALE: Giving chemotherapy, such as fludarabine and busulfan, before a donor peripheral stem cell transplant helps stop the growth of cancer or abnormal cells. It also helps stop the patient's immune system from rejecting the donor's 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. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells. Giving a monoclonal antibody, alemtuzumab, before the transplant and tacrolimus after the transplant may stop this from happening.

PURPOSE: The phase I portion of this trial identified the maximum tolerated dose of busulfan after treating 40 patients on a dose-escalation scheme. We are now treating an additional 26 patients on the phase II portion of the trial at a Pharmacokinetic (PK)-directed dose of total area under curve (AUC) 6912 micrometer (uM)-min/24 hours. We transitioned to the Phase II portion of the study in October 2009.

Conditions

• Chronic Myeloproliferative Disorders
• Leukemia
• Lymphoma
• Multiple Myeloma and Plasma Cell Neoplasm
• Myelodysplastic Syndromes

Interventions

BIOLOGICAL

rabbit anti-thymocyte globulin (ATG)

.5 mg/kg on day -3 and 2.5 mg/kg on day -2

BIOLOGICAL

therapeutic allogeneic lymphocytes

minimum total cluster of differentiation (CD34+) cells of 3 x 10\^6 cells/kg and a maximum of 8 x 10\^6 cells/kg will be infused on day 0

DRUG

busulfan

PK-targeted continuous IV infusion over 90 hours on Days -7 to -4.

DRUG

fludarabine phosphate

30 mg/m\^2/day x 5 days intravenous piggyback (IVPB) over 30 minutes on Days -7 through -3

DRUG

tacrolimus

The suggested starting dose is 0.03 mg/kg po bid starting on day -1

PROCEDURE

allogeneic hematopoietic stem cell transplantation

A minimum total CD34+ cell dose of 3 x 10\^6 cells/kg and maximum of 8 x 10\^6 cells/kg will be infused on day 0

PROCEDURE

peripheral blood stem cell transplantation

minimum total CD34+ cell dose of 3 x 10\^6 cells/kg and a maximum of 8 x 10\^6 cells/kg will be infused on day 0

DRUG

methotrexate

5 mg/m\^2 on days +1, +3 and +6

Sponsors & Collaborators

• National Cancer Institute (NCI)

  collaborator NIH

• Otsuka America Pharmaceutical

  collaborator INDUSTRY

• UNC Lineberger Comprehensive Cancer Center

  lead OTHER

Principal Investigators

• Thomas C. Shea, MD · UNC Lineberger Comprehensive Cancer Center

Study Design

Allocation

NA

Purpose

TREATMENT

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Min Age

18 Years

Max Age

55 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2005-10-31

Primary Completion

2015-11-30

Completion

2015-11-30

Countries

• United States

Study Locations