Last updated on January 2020

Hematopoietic Stem Cell Transplant for Sickle Cell Disease

Brief description of study

This is a phase I/II study of patients with sickle cell disease. It aims to find out if people with sickle cell disease can be cured by changing their immune system before they have blood stem cell transplants. Doctors will give patients a new drug (fludarabine) to see if this drug changes patients immune system and reduces the patient's cells (host) from rejecting donor cells (graft) after the patient gets a Hematopoietic (blood) stem cell transplant.

Detailed Study Description

Primary Objective

  1. To evaluate the safety and feasibility of hematopoietic stem cell transplant (HSCT) after treatment with fludarabine in adult patients with Sickle Cell Disease (SCD).

Secondary Objective(s), in HSCT for SCD

  1. To evaluate the rates of disease-free and overall survival in both MSD and alternate graft donor (MUD, haploidentical, or cord blood-derived) recipients
  2. To evaluate fertility in matched sibling and alternate-donor graft recipients
  3. To evaluate GVHD rates in MSD and Alternate Graft Donor recipients in SCD.
  4. To evaluate cerebral, pulmonary, renal, and generalized vasculopathy before and after HSCT in SCD.
  5. To evaluate hematopoiesis and erythropoiesis before and before HSCT in SCD.
  6. Modulation of SCD Phenotype by Allogeneic Transplantation. Rigorous clinical follow-up will be performed, per routine care, to evaluate those consequences of SCD that will be modified by allogeneic transplantation in the short-term (4-12 weeks), in the medium-term (12-24 weeks) and in the long-term (>24 weeks). Short-term changes would include disappearance of stress hematopoiesis and erythropoiesis; medium- and long-term changes would include effects on pain, fertility (TSH, LH), cognition (routine cognitive assessments), and end-organ damage (including urine albumin-to-creatinine ratios and tricuspid regurgitant jet velocities, as indicated).

The study will start with at least 10 and up to 25 patients. They will be given the lowest starting dose of fludarabine. This is done to make sure it is safe. Researchers will watch the patients during what is called the dose-limiting toxicity (DLT) period. Their safety will be monitored by a Safety Monitoring Committee, which is made up of people who run research studies. The study will not take new patients until the DLT period is done.

If at least 3 of the 10 patients enrolled do not benefit, the maximum tolerated dose (MTD) will be considered exceeded. After the DLT period is complete, patients will receive a stem cell transplant from a genetically matched donor. Patients will be continued to be monitored for a year after the transplant.

To prepare for the transplant patients will have to undergo the following treatments:

  • an exchange transfusion
  • a stem cell graft infusion from either a:
  • perfectly matched sibling donor (called MSD),
  • perfectly matched but unrelated donor (called MUD),
  • a half-matched related donor (called Haploidentical), or
  • a cord blood donor
  • rabbit antithymocyte globulin (ATG)
  • cytoxan (a type of chemotherapy)
  • Fludarabine (you get this medicine a few weeks before transplant and again, as part of the routine chemotherapy treatment). This is the main drug being studies in this research
  • total body irradiation (also called TBI)
  • tacrolimus, mycophenolate (MMF) and/or methotrexate (MTX). These drugs will weaken your immune system. They are given to lower your chances of getting GVHD and rejecting the donor cells.

Patients will be in the study for approximately 14 months.

Clinical Study Identifier: NCT02065596

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