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Sickle Cell DiseasePhase 2DREPHAPLONCT03240731

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

A Phase 2 study testing bone marrow transplant in people with Sickle Cell Disease, run by Centre Hospitalier Intercommunal Creteil at 7 sites in France.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 13 to 40 years
Conditions the study is for
Sickle Cell Disease
What is being tested?
bone marrow transplant
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
25 participants
Where
7 sitesFrance
Study dates
10 Aug 2017to 8 Apr 2024
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 13 to 40 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

Who may be able to join

  • 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
Show all 23Show fewer
  • 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)
  • 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)
  • Lack antigens HLA recognized by the recipient antibody
  • Hemoglobin S <50%
  • When several donors are compatible: choose according to the ABO recipient: prefer ABO compatibility and major incompatibility and minor incompatibility, and finally major and minor incompatibility.
  • Signature of informed consent
  • Non-inclusion criteria donors: β HCG positive or known pregnancy

Who cannot join

  • 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%
Show all 12Show fewer
  • 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
  • severe uncontrolled infection at the time of inclusion or graft
  • pregnant woman (positive beta HCG) or during lactation
  • incapable adult patient, trust, guardianship, or safeguard justice

Trial locations and contacts

7 sites in 1 country.

7 sites in 1 country

France7 sites

  • CHU Henri-Mondor

    Créteil, 94000

  • intercommunal hospital of Créteil

    Créteil, 94000

  • CHU La Timone

    Marseille

  • Hospital Necker

    Paris

  • Hospital Robert-Debré

    Paris

  • Saint-Louis hospital

    Paris

  • CHU Strasbourg

    Strasbourg

Other trials in France

About this study

Official title: Bone Marrow Transplantation HLA Haploidentical After a Reduced Intensity Conditioning and Prevention of GvHD Based on Post-transplant Cyclophosphamide Administration in Patients With Severe Sickle Cell Disease

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.

Read the detailed description

Sickle cell disease is a severe disease with frequent occurrence of painful crises and progressive installation of a multi organ injuries. Despite the progress in its management, particularly since the introduction of hydroxycarbamide, the median age of death in sickle cell patients was about 40 years in a recent US study. Severe forms resistant to hydroxyurea or cerebral vasculopathy require transfusion programs throughout susceptible to risks of iron overload and alloimmunization. The bone marrow transplantation cures almost 95% of children and adolescents transplant from an HLA-identical siblings. In patients without HLA-identical donor, interesting results have been reported in haploidentical transplants marrow without ex vivo T cell depletion taken after non myeloablative conditioning regimen and GvHD prevention with cyclophosphamide high dose injection after bone marrow transplant . This approach performed in 14 patients was effective to cure 50% of the patients and 50% have rejected the transplant . No death or severe GvHD were related to the procedure.

DREPHAPLO protocol aims to evaluate that approach in a population of sickle cell patients with severe complications of the disease, bringing direct benefit to patients with a cure of the disease in at least half of them.

Being tested
bone marrow transplant
Keywords
sickle cell disease, haploidentical, graft, marrow
Medical subject headings
Anemia, Sickle Cell

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • bone marrow transplantBiological

    haploidentical bone marrow transplant

Study groups in NCT03240731
Study groupRoleWhat they receive
bone marrow transplantExperimentalAll 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.
Receives: Biological: bone marrow transplant

What is being measured

The primary outcome is the main question the study is designed to answer.

  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

    Measured: 2 years

Secondary outcomes (31)

  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

    Measured: 1 year

  2. haematologic reconstitution

    defined as a neutrophil count> 500 / mm3 and platelets> 20000 / mm3, for three consecutive days.

    Measured: 2 years

  3. Chimerism

    Chimerism in the peripheral blood of the total population and the CD3 + population with the techniques usually employed by the centers

    Measured: at month 1

  4. Chimerism

    Chimerism in the peripheral blood of the total population and the CD3 + population with the techniques usually employed by the centers

    Measured: at month 2

  5. Chimerism

    Chimerism in the peripheral blood of the total population and the CD3 + population with the techniques usually employed by the centers

    Measured: at month 3

  6. Chimerism

    Chimerism in the peripheral blood of the total population and the CD3 + population with the techniques usually employed by the centers

    Measured: at month 4

  7. Chimerism

    Chimerism in the peripheral blood of the total population and the CD3 + population with the techniques usually employed by the centers

    Measured: at month 5

  8. Chimerism

    Chimerism in the peripheral blood of the total population and the CD3 + population with the techniques usually employed by the centers

    Measured: at month 6

  9. Chimerism

    Chimerism in the peripheral blood of the total population and the CD3 + population with the techniques usually employed by the centers

    Measured: at month 9

  10. Chimerism

    Chimerism in the peripheral blood of the total population and the CD3 + population with the techniques usually employed by the centers

    Measured: at month 12

  11. Chimerism

    Chimerism in the peripheral blood of the total population and the CD3 + population with the techniques usually employed by the centers

    Measured: at month 24

  12. hemoglobin electrophoresis

    Measured: at 1 month

  13. hemoglobin electrophoresis

    Measured: at 2 month

  14. hemoglobin electrophoresis

    Measured: at 3 months

  15. hemoglobin electrophoresis

    Measured: at 4 months

  16. hemoglobin electrophoresis

    Measured: at 5 months

  17. hemoglobin electrophoresis

    Measured: at 6 months

  18. hemoglobin electrophoresis

    Measured: at 9 months

  19. hemoglobin electrophoresis

    Measured: at 12 months

  20. hemoglobin electrophoresis

    Measured: at 24 months

  21. occurence of graft versus host disease

    evaluated monthly from M1 to M6, and M9, M12, M24

    Measured: at month 24

  22. grade of graft versus host disease

    Incidence and grade of GvHD, toxic deaths and infectious complications and secondary cancer

    Measured: at month 24

  23. occurrence of toxic deaths

    Measured: at month 24

  24. occurrence of infectious complications

    Measured: at month 24

  25. occurrence of secondary cancer

    Measured: at month 24

  26. Lymphocyte immunophenotyping

    Lymphocyte immunophenotyping T, B and NK + The Extended Phenotype including activation markers, assessment of naive people and memories, T reg populations etc) and plasma protein electrophoresis: 1 month, 3 months, 6 months, 12 months and 24 months post-transplantation.

    Measured: 2 years

  27. ECOG score value

    Index Trading ECOG complete physical examination with determination of weight

    Measured: 2 years

  28. Assessment of sickle cell disease complications

    Microalbuminuria, creatinuria; echocardiography for measurement of systolic ventricular ejection fraction (February), PAH research and measurement IT Vmax; respiratory function tests with measurement of DLCO; MRI brain with ARM and Cervical Pre-transplant anomalies; Radio of the pelvis

    Measured: at 1 year

  29. ferritin dosage

    Evaluation of iron overload by ferritin

    Measured: at month 3

  30. ferritin dosage

    Evaluation of iron overload by ferritin

    Measured: at month 6

  31. MRI iron overload

    hepatic and cardiac MRI to assess the iron overload

    Measured: at 12 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted7 Aug 2017
  2. Study start10 Aug 2017
  3. Primary completion8 Apr 2024
  4. Study completion8 Apr 2024

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Other
Allocation
Not applicable
Intervention model
Single group
Model description
Haploidentical Marrow Transplants
Masking
None (open label)
Enrolment
25 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03240731
Sponsor's protocol ID
DREPHAPLO
Acronym
DREPHAPLO
Status last verified
Aug 2025
First submitted
31 Jul 2017
Last updated
2 Sep 2025
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Yawn BP, Buchanan GR, Afenyi-Annan AN, Ballas SK, Hassell KL, James AH, Jordan L, Lanzkron SM, Lottenberg R, Savage WJ, Tanabe PJ, Ware RE, Murad MH, Goldsmith JC, Ortiz E, Fulwood R, Horton A, John-Sowah J. Management of sickle cell disease: summary of the 2014 evidence-based report by expert panel members. JAMA. 2014 Sep 10;312(10):1033-48. doi: 10.1001/jama.2014.10517.

    PubMed 25203083

  • Habibi A, Arlet JB, Stankovic K, Gellen-Dautremer J, Ribeil JA, Bartolucci P, Lionnet F; centre de reference maladies rares << syndromes drepanocytaires majeurs >>. [French guidelines for the management of adult sickle cell disease: 2015 update]. Rev Med Interne. 2015 May 11;36(5 Suppl 1):5S3-84. doi: 10.1016/S0248-8663(15)60002-9. French.

    PubMed 26007619

  • Lanzkron S, Carroll CP, Haywood C Jr. Mortality rates and age at death from sickle cell disease: U.S., 1979-2005. Public Health Rep. 2013 Mar-Apr;128(2):110-6. doi: 10.1177/003335491312800206.

    PubMed 23450875

  • Bernaudin F, Socie G, Kuentz M, Chevret S, Duval M, Bertrand Y, Vannier JP, Yakouben K, Thuret I, Bordigoni P, Fischer A, Lutz P, Stephan JL, Dhedin N, Plouvier E, Margueritte G, Bories D, Verlhac S, Esperou H, Coic L, Vernant JP, Gluckman E; SFGM-TC. Long-term results of related myeloablative stem-cell transplantation to cure sickle cell disease. Blood. 2007 Oct 1;110(7):2749-56. doi: 10.1182/blood-2007-03-079665. Epub 2007 Jul 2.

    PubMed 17606762

  • Kuentz M, Robin M, Dhedin N, Hicheri Y, Peffault de Latour R, Rohrlich P, Bordigoni P, Bruno B, Socie G, Bernaudin F. Is there still a place for myeloablative regimen to transplant young adults with sickle cell disease? Blood. 2011 Oct 20;118(16):4491-2; author reply 4492-3. doi: 10.1182/blood-2011-07-367490. No abstract available.

    PubMed 22021455

  • Angelucci E, Matthes-Martin S, Baronciani D, Bernaudin F, Bonanomi S, Cappellini MD, Dalle JH, Di Bartolomeo P, de Heredia CD, Dickerhoff R, Giardini C, Gluckman E, Hussein AA, Kamani N, Minkov M, Locatelli F, Rocha V, Sedlacek P, Smiers F, Thuret I, Yaniv I, Cavazzana M, Peters C; EBMT Inborn Error and EBMT Paediatric Working Parties. Hematopoietic stem cell transplantation in thalassemia major and sickle cell disease: indications and management recommendations from an international expert panel. Haematologica. 2014 May;99(5):811-20. doi: 10.3324/haematol.2013.099747.

    PubMed 24790059

  • Hsieh MM, Fitzhugh CD, Weitzel RP, Link ME, Coles WA, Zhao X, Rodgers GP, Powell JD, Tisdale JF. Nonmyeloablative HLA-matched sibling allogeneic hematopoietic stem cell transplantation for severe sickle cell phenotype. JAMA. 2014 Jul 2;312(1):48-56. doi: 10.1001/jama.2014.7192.

    PubMed 25058217

  • Bolanos-Meade J, Fuchs EJ, Luznik L, Lanzkron SM, Gamper CJ, Jones RJ, Brodsky RA. HLA-haploidentical bone marrow transplantation with posttransplant cyclophosphamide expands the donor pool for patients with sickle cell disease. Blood. 2012 Nov 22;120(22):4285-91. doi: 10.1182/blood-2012-07-438408. Epub 2012 Sep 6.

    PubMed 22955919

  • Kamani NR, Walters MC, Carter S, Aquino V, Brochstein JA, Chaudhury S, Eapen M, Freed BM, Grimley M, Levine JE, Logan B, Moore T, Panepinto J, Parikh S, Pulsipher MA, Sande J, Schultz KR, Spellman S, Shenoy S. Unrelated donor cord blood transplantation for children with severe sickle cell disease: results of one cohort from the phase II study from the Blood and Marrow Transplant Clinical Trials Network (BMT CTN). Biol Blood Marrow Transplant. 2012 Aug;18(8):1265-72. doi: 10.1016/j.bbmt.2012.01.019. Epub 2012 Feb 16.

    PubMed 22343376

  • Luznik L, O'Donnell PV, Symons HJ, Chen AR, Leffell MS, Zahurak M, Gooley TA, Piantadosi S, Kaup M, Ambinder RF, Huff CA, Matsui W, Bolanos-Meade J, Borrello I, Powell JD, Harrington E, Warnock S, Flowers M, Brodsky RA, Sandmaier BM, Storb RF, Jones RJ, Fuchs EJ. HLA-haploidentical bone marrow transplantation for hematologic malignancies using nonmyeloablative conditioning and high-dose, posttransplantation cyclophosphamide. Biol Blood Marrow Transplant. 2008 Jun;14(6):641-50. doi: 10.1016/j.bbmt.2008.03.005.

    PubMed 18489989

  • McCurdy SR, Kanakry JA, Showel MM, Tsai HL, Bolanos-Meade J, Rosner GL, Kanakry CG, Perica K, Symons HJ, Brodsky RA, Gladstone DE, Huff CA, Pratz KW, Prince GT, Dezern AE, Gojo I, Matsui WH, Borrello I, McDevitt MA, Swinnen LJ, Smith BD, Levis MJ, Ambinder RF, Luznik L, Jones RJ, Fuchs EJ, Kasamon YL. Risk-stratified outcomes of nonmyeloablative HLA-haploidentical BMT with high-dose posttransplantation cyclophosphamide. Blood. 2015 May 7;125(19):3024-31. doi: 10.1182/blood-2015-01-623991. Epub 2015 Mar 26.

    PubMed 25814532

  • Bashey A, Zhang X, Sizemore CA, Manion K, Brown S, Holland HK, Morris LE, Solomon SR. T-cell-replete HLA-haploidentical hematopoietic transplantation for hematologic malignancies using post-transplantation cyclophosphamide results in outcomes equivalent to those of contemporaneous HLA-matched related and unrelated donor transplantation. J Clin Oncol. 2013 Apr 1;31(10):1310-6. doi: 10.1200/JCO.2012.44.3523. Epub 2013 Feb 19.

    PubMed 23423745

  • Bashey A, Zhang X, Jackson K, Brown S, Ridgeway M, Solh M, Morris LE, Holland HK, Solomon SR. Comparison of Outcomes of Hematopoietic Cell Transplants from T-Replete Haploidentical Donors Using Post-Transplantation Cyclophosphamide with 10 of 10 HLA-A, -B, -C, -DRB1, and -DQB1 Allele-Matched Unrelated Donors and HLA-Identical Sibling Donors: A Multivariable Analysis Including Disease Risk Index. Biol Blood Marrow Transplant. 2016 Jan;22(1):125-33. doi: 10.1016/j.bbmt.2015.09.002. Epub 2015 Sep 7.

    PubMed 26359881

  • Ciurea SO, Mulanovich V, Saliba RM, Bayraktar UD, Jiang Y, Bassett R, Wang SA, Konopleva M, Fernandez-Vina M, Montes N, Bosque D, Chen J, Rondon G, Alatrash G, Alousi A, Bashir Q, Korbling M, Qazilbash M, Parmar S, Shpall E, Nieto Y, Hosing C, Kebriaei P, Khouri I, Popat U, de Lima M, Champlin RE. Improved early outcomes using a T cell replete graft compared with T cell depleted haploidentical hematopoietic stem cell transplantation. Biol Blood Marrow Transplant. 2012 Dec;18(12):1835-44. doi: 10.1016/j.bbmt.2012.07.003. Epub 2012 Jul 11.

    PubMed 22796535

  • Raiola AM, Dominietto A, Ghiso A, Di Grazia C, Lamparelli T, Gualandi F, Bregante S, Van Lint MT, Geroldi S, Luchetti S, Ballerini F, Miglino M, Varaldo R, Bacigalupo A. Unmanipulated haploidentical bone marrow transplantation and posttransplantation cyclophosphamide for hematologic malignancies after myeloablative conditioning. Biol Blood Marrow Transplant. 2013 Jan;19(1):117-22. doi: 10.1016/j.bbmt.2012.08.014. Epub 2012 Aug 29.

    PubMed 22940057

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing bone marrow transplant in people with Sickle Cell Disease, run by Centre Hospitalier Intercommunal Creteil at 7 sites in France.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 23 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 2 Sep 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 7 sites in France. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Survival rate (time frame: 2 years). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03240731, which also lists 26 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Sep 2025.

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