Non-Myeloablative Conditioning and Bone Marrow Transplantation

Summary

Allogeneic blood or marrow transplantation (alloBMT) is a curative therapy for a variety of hematologic disorders, including sickle cell disease and thalassemia. Even when it is clear that alloBMT can give to these patients an improvement in their disease, myeloablative transplants have important toxicities and mortalities associated. The lack of suitable donors continues to be a limit to access to transplantation. Substantial progress has been made recently in the development of pre-treatment regimens that facilitate the sustained engraftment of donor marrow with reduced toxicity. Most of these regimens incorporate highly immunosuppressive drugs, which allow the reduction or elimination of myeloablative agents or total body irradiation without endangering the sustained engraftment of HLA-identical allogeneic stem cells. Preliminary results of non-myeloablative allogeneic stem cell transplantation suggest that the procedure can be performed in patients who are ineligible for myeloablative alloBMT, and that sustained remissions of several hematologic malignancies can be obtained.

Conditions

• Sickle Cell Disease
• Hemoglobinopathies

Interventions

DRUG

Thymoglobulin

Day 9 before BMT: 0.5mg/kg IV; Days 8 \& 7 before BMT: 2mg/kg IV Days 8 \& 7 - 2mg/kg IV before BMT

DRUG

Fludarabine

Days 6 and 2 before BMT: 30mg/m2/day IV

DRUG

Cyclophosphamide (CTX)

Days 6 and 5 before BMT: 14.5mg/kg IV; Days 3 and 4 after BMT: 50mg/kg/day

DRUG

Mesna

Days 3 \& 4 after BMT: 40 mg/kg IV

DRUG

Sirolimus

Adjusted to maintain a serum trough level of 3-12 ng/mL, taken orally beginning on 5 days after BMT and taken to 1 year after BMT.

DRUG

Mycophenolate mofetil (MMF)

15 mg/kg orally with maximum dose 3 mg/day beginning 5 days after BMT and taken to day 35 after BMT

PROCEDURE

Bone marrow transplantation

Day 0 - Transplantation of hematopoietic cells derived from bone marrow of a donor to a recipient as treatment for hematologic disorders

RADIATION

Total body irradiation

200 cGy on the day before BMT. Radiation delivered to the entire body of the recipient to eradicate bone marrow cells in the recipient to prepare the recipient to receive the transplanted

Sponsors & Collaborators

• Vanderbilt-Ingram Cancer Center

  lead OTHER

Principal Investigators

• Adetola A Kassim, MD · Vanderbilt-Ingram Cancer Center

Study Design

Allocation

NA

Purpose

TREATMENT

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Min Age

1 Year

Max Age

70 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2013-05-31

Primary Completion

2023-11-30

Completion

2024-12-31

Countries

• United States
• France
• United Kingdom

Study Locations