HLA Haploidentical Bone Marrow Transplant in Patients With Severe Sickle Cell Disease

NCT03240731 | Completed Phase 2 DMC

• 1 other identifier: DREPHAPLO
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 7

Brief Summary

multicentric interventional biomedical research phase II, prospective, non-randomized evaluating a haploidentical marrow transplants after reduced-intensity conditioning and prevention of GvHD based on cyclophosphamide administration post transplantation in patients with severe sickle cell disease.

Conditions

Sickle Cell Disease

Keywords

sickle cell disease; haploidentical; graft; marrow

Outcome Measures

Primary Outcomes (1)

• Survival rate

  Survival without sickle cell survival rate (electrophoresis of hemoglobin similar to that from the donor, that is to say a percentage of HbS not exceeding 10% of that of distance donor transfusions and that of a stable manner and without GvHDc other than mild

  2 years

Secondary Outcomes (31)

• Survival rate

  1 year

• haematologic reconstitution

  2 years

• Chimerism

  at month 1

• Chimerism

  at month 2

• Chimerism

  at month 3

Study Arms (1)

bone marrow transplant

EXPERIMENTAL

All the included patient will receive an haploidentical bone marrow transplant with the following protocol concerning the conditioning and GvHD prevention Conditioning * THYMOGLOBULINE : 0.5mg/kg at D-9 and 2 mg/kg at D-8 and D-7 * THIOTEPA: 10mg/kg/j at D-7 * CYCLOPHOSPHAMIDE (Endoxan®):14.5mg/kg/j at D-6 and D-5 * FLUDARABINE (Fludara®): 30mg/m2 per Day from D-6 to D-2 * TBI : 2GY : D -1 Graft : Injection at D0 of G-CSF-stimulated bone marrow transplant. Prophylaxis of GvHD * CYCLOPHOSPHAMIDE (Endoxan®): 50mg/Kg per Day from D+3 to D+4 * Sirolimus and MycophénolateMofétil (MMP) from D+5. In the absence of acute GvHD (aGvHD), stop of MMP to D35 and pursuit of sirolimus 1 year after the graft.

Biological: bone marrow transplant

Interventions

bone marrow transplant BIOLOGICAL

haploidentical bone marrow transplant

bone marrow transplant

Eligibility Criteria

• Age: 13 Years - 40 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Age: 13 years-40 years
• Severe Sickle cell with at least one of the following criteria:
• Stenosing vasculopathy with abnormal MRA despite prolonged transfusion program
• PAH confirmed by right catheterization with mPAP\> 25mmHg
• Systolic ejection fraction \<55% and tricuspid regurgitation speed\> 2.5m /s at distance from an acute episode
• No possibility of blood transfusion or very complicated blood transfusion
• Report albumin / creatinine\> 30 mg / mmol, confirmed 3 times, away at distance from acute episode and persistent despite hydroxyurea or IEC
• GFR \<80ml / min /1.73m2 (CKD-Epi without ethnic criterion)
• Previous history of acute liver sequestration with liver failure
• Acute chest syndrome or vaso-occlusive crises under hydroxyurea
• Complications of sickle cell transfusion imposing an exchange program with no possible withdrawal beyond a period of one year
• Not having geno-identical donor, but a haploidentical major donor (parent, sibling, adult child, or HbAA AS)
• Having red and understood the information letter and signed the informed consent
• Patients affiliated to a social security system (Social Security or Universal Medical Coverage)

You may not qualify if:

• Patient with a geno-identical donor
• Performans status: ECOG\> 1
• lung disease: FEV1 and FVC \<50% predicted,
• score of PAH NYHA≥2
• Liver disease with bilirubin\> 50 .mu.mol / L
• heart failure defined by NYHA≥3 score ejection fraction \<45% or shortening fraction \<24%
• anti HLA alloimmunization against the donor or against red cell antigens of the donor
• Serology or HIV viral load positively
• Patients who for family, social or geographical reasons, do not wish to be regularly monitored in consultation
• pregnant woman (positive beta HCG) or during lactation
• incapable adult patient, trust, guardianship, or safeguard justice
• Age\> 18 years and \<60 years
• Viral serologic economy allows the graft
• No contraindication for general anesthesia
• No contraindication the administration of G-CSF (the existence of sickle cell trait is not a contraindication)

Sponsors & Collaborators

• Centre Hospitalier Intercommunal Creteil: lead
• Keocyt: collaborator
• Association Clinique Thérapeutique Infantile du val de Marne: collaborator

Study Sites (7)

CHU Henri-Mondor

Créteil, 94000, France

Location

intercommunal hospital of Créteil

Créteil, 94000, France

Location

CHU La Timone

Marseille, France

Location

Hospital Necker

Paris, France

Location

Hospital Robert-Debré

Paris, France

Location

Saint-Louis hospital

Paris, France

Location

CHU Strasbourg

Strasbourg, France

Location

Related Publications (26)

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MeSH Terms

Conditions

Anemia, Sickle Cell

Interventions

Bone Marrow Transplantation

Condition Hierarchy (Ancestors)

Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemoglobinopathies; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Tissue Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Therapeutics; Transplantation; Surgical Procedures, Operative

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: Haploidentical Marrow Transplants

Study Record Dates

• First Submitted: July 31, 2017
• First Posted: August 7, 2017
• Study Start: August 10, 2017
• Primary Completion: April 8, 2024
• Study Completion: April 8, 2024
• Last Updated: September 2, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

FR (7)