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HLA-Identical Sibling Donor Bone Marrow Transplantation for Individuals With Severe Sickle Cell Disease Using a Reduced Intensity Conditioning Regimen

NCT02776202 · Status: UNKNOWN · Phase: PHASE2 · Type: INTERVENTIONAL · Enrollment: 15

Last updated 2016-05-19

No results posted yet for this study

Summary

Sickle cell disease (SCD) is the most common inherited blood disorder in Saudi Arabia . Its clinical severity is widely heterogeneous among patients who share the same genetic mutation . Severe frequent pain crisis, recurrent acute chest syndrome and stroke are features of severe SCD. Hydroxyurea is an effective treatment of SCD as it ameliorates the severity and frequency of pain crisis and acute chest syndrome and decreases mortality, however, it is less effective in the prevention and treatment of stroke and other end organ dysfunctions . The only readily available cure of SCD is by hematopoietic stem cell transplantation (HSCT) . Most children with SCD who are treated by HSCT receive myeloablative conditioning with excellent results. The application of reduced intensity (RIC) and non-myeloablative (NMA) conditioning regimens are reserved for patients older than 16 years of age because of the increased risks of morbidity and mortality after HSCT6. However, infertility and gonadal failure after myeloablative conditioning are important barriers to the willingness of patients and their families to undergo HSCT . The development of an effective RIC HSCT in SCD that might spare the fertility of SCD patients would have obvious merit.

With the ultimate goal of expanding this curative therapy to SCD patients, we propose to investigate HSCT with a RIC conditioning regimen. We will carry out a pilot study of HSCT from HLA matched sibling donors using thymoglobulin/fludarabine/melphalan conditioning and sirolimus and mycophenolate mofetil (MMF) as GVHD prophylaxis in SCD patients with severe complications such as stroke and other severe complications. We hypothesize that HSCT from HLA matched sibling using thymoglobulin/fludarabine/melphalan conditioning in SCD will maintain a level of stable donor chimerism that is sufficient to cure SCD with minimal toxicity.

Conditions

Interventions

DRUG

Fludarabine monophosphate

The HSCT preparative regimen will consist of * Thymoglobulin: 2.5 mg /kg/day intravenously (IV) on Days -8 through -5 * Fludarabine: 35 mg/m2/day IV on Days -8 through -4 * Melphalan: 140 mg/m2 IV on Day -3 * Rest on Day -2 and -1 * Day 0 is the day of transplant * GVHD prophylaxis: sirolimus beginning on Day -1 for at least one year and mycophenolate mofetil (MMF) from Day -3 to +45 or to 7 days after neutrophil engraftment, whichever is later.

Sponsors & Collaborators

  • National Guard Health Affairs

    lead OTHER_GOV

Study Design

Allocation
NA
Purpose
TREATMENT
Masking
NONE
Model
SINGLE_GROUP

Eligibility

Min Age
3 Years
Max Age
18 Years
Sex
ALL
Healthy Volunteers
No

Timeline & Regulatory

Start
2016-05-31
Primary Completion
2019-12-31
Completion
2019-12-31

Countries

  • Saudi Arabia

Study Locations

More Related Trials

Entities

Diseases

Read the full study record

This page highlights key information. For complete eligibility criteria, study locations, investigator contacts, and the full protocol, visit the original record on ClinicalTrials.gov.

View NCT02776202 on ClinicalTrials.gov