Transplantation for Patients With Sickle Cell Disease From Mismatched Family Donors of Bone Marrow

Summary

The purpose of this study is to learn if it is possible and safe to treat persons with severe sickle cell disease (SCD) by bone marrow transplant (BMT) from human leukocyte antigen (HLA) half-matched related donors. Preparation before transplant includes the chemotherapy drugs hydroxyurea, fludarabine, thiotepa, anti-thymocyte globulin, and cyclophosphamide. It also includes radiation.

Conditions

• Sickle Cell Disease

Interventions

PROCEDURE

Bone Marrow Transplant (BMT)

Participants will receive a bone marrow infusion from a human leukocyte antigen (HLA) mismatched donor through a central venous catheter.

DRUG

Hydroxyurea

Hydroxyurea is part of the bone marrow transplant preparative regimen. Hydroxyurea will be administered at a dose of 30 mg/kg orally as a single daily dose for 90 days (from day -100 to day-10). Hydroxyurea dosing will be based on adjusted body weight in participants weighing \>125% ideal body weight.

DRUG

Thiotepa

Thiotepa is part of the bone marrow transplant preparative regimen. Thiotepa will be administered at a dose of 10mg/kg intravenously (IV) over 2 hours or per institutional guidelines on day -7. Thiotepa dosing will be based on adjusted body weight in patients weighing \>125% ideal body weight.

DRUG

Fludarabine monophosphate

Fludarabine is part of the bone marrow transplant preparative regimen. Fludarabine 30 mg/m2/day will be administered from day -7 to day -3 (for a total of 150 mg/m2 over 5 consecutive days) and administered intravenously (IV) over a minimum of 30 minutes. In participants weighing \> 125% ideal body weight, fludarabine will be dose based upon adjusted body weight.

DRUG

Cyclophosphamide

Cyclophosphamide is part of the bone marrow transplant preparative regimen. Cyclophosphamide will be administered on days -6 and -5 prior to bone marrow infusion at a dose of 14.5 mg/kg intravenously (IV) infused over 1-2 hours. Post bone marrow infusion cyclophosphamide will be infused on days +3 (between 60 and 72 hours post marrow infusion) and +4 (approximately 24 hours after day +3 dose) at a dose of 50 mg/kg IV infused over 1-2 hours. For participants weighing more than 125% of their ideal body weight, dosing will be based on adjusted ideal body weight.

OTHER

Rabbit Anti-thymocyte Globulin

Rabbit anti-thymocyte globulin (ATG) is part of the bone marrow transplant preparative regimen. It is an infusion of rabbit-derived antibodies against human T cells used for prevention of acute rejection in organ transplantation. Rabbit ATG will be administered on day -9 at 0.5 mg/kg and on days -8 and -7 at 2 mg/kg (for a total dose 4.5 mg/kg).

RADIATION

Total Body Irradiation

Participants will receive 200 cGy of TBI in a single fraction.

Sponsors & Collaborators

• Emory University

  lead OTHER

Principal Investigators

• Lakshmanan Krishnamurti, MD · Emory University

Study Design

Allocation

NA

Purpose

TREATMENT

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Min Age

15 Years

Max Age

40 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2019-07-10

Primary Completion

2021-12-12

Completion

2021-12-14

FDA Drug

Yes

Countries

• United States

Study Locations