Post Transplant Cyclophosphamide in Matched Unrelated Donor Stem Cell Transplantation for Hematological Malignancies

Graft Versus Host Disease Clinical Trial

Official title:

Use of Post Transplant Cyclophosphamide as Graft Versus Host Disease Prophylaxis in Matched Unrelated Donor Stem Cell Transplantation for Hematological Malignancies, a Prospective Randomized Controlled Trial

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03818334
• Other study ID #: SGPP 3549-18
• Status: Recruiting
• Phase: Phase 2/Phase 3
• Start date: November 6, 2018
• Est. completion date: November 1, 2026

Study information

• Verified date: January 2019
• Source: Hospital Israelita Albert Einstein
• Contact: Andreza A Feitosa Ribeiro
• Phone: +5511992512523
• Email: andreza.ribeiro[@]einstein.br
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study aims to evaluate the clinical efficacy of cyclophosphamide in patients receiving a bone marrow graft from a matched unrelated donor in overall survival, progression free survival and cumulative incidence of acute and chronic GvHD. Thirty patients will receive cyclophosphamide while twenty patients will receive antihuman T-lymphocyte immune globulin (ATG).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 50
• Est. completion date: November 1, 2026
• Est. primary completion date: November 1, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 1 Year to 75 Years

Eligibility

Inclusion Criteria:

• Men and Women of Any Age

• Indication for an HSCT without matched sibling donor

• Have a matched unrelated donor (HLA 10 x 10 or 9 x 10)

• Hematological malignancy

Exclusion Criteria:

• Acute leukemias not in complete response (that is > 5% blast in the bone marrow)

• Chemorefractory lymphoproliferative disease

• Active uncontrolled infection

• HCT-CI > 3

• Severe organic disfunction (heart ejection fraction < 45%, glomerular filtration rate < 50 mL.hour, pulmonary DLCO < 50%)

• Previous allogeneic bone marrow transplantation

• Contraindication to cyclophosphamide or ATG

Related Conditions & MeSH terms

• Bone Marrow Transplant Complications
• Engraft Failure
• Graft Versus Host Disease
• Graft vs Host Disease
• Immunologic Suppression
• Infection Viral
• Neoplasms
• Virus Diseases

Intervention

Drug:
• Cyclophosphamide
Cyclophosphamide 1000 mg/flask
• ATG
Antihuman T-Lymphocyte Immune Globulin 25 mg/flask

Locations

Country	Name	City	State
Brazil	Hospita Israelita Albert Eintein	São Paulo	SP

Sponsors (1)

Lead Sponsor	Collaborator
Hospital Israelita Albert Einstein

Country where clinical trial is conducted

Brazil, 

References & Publications (8)

Bacigalupo A, Lamparelli T, Barisione G, Bruzzi P, Guidi S, Alessandrino PE, di Bartolomeo P, Oneto R, Bruno B, Sacchi N, van Lint MT, Bosi A; Gruppo Italiano Trapianti Midollo Osseo (GITMO). Thymoglobulin prevents chronic graft-versus-host disease, chronic lung dysfunction, and late transplant-related mortality: long-term follow-up of a randomized trial in patients undergoing unrelated donor transplantation. Biol Blood Marrow Transplant. 2006 May;12(5):560-5. — View Citation

Devillier R, Labopin M, Chevallier P, Ledoux MP, Socié G, Huynh A, Bourhis JH, Cahn JY, Roth-Guepin G, Mufti G, Desmier D, Michallet M, Fegueux N, Ciceri F, Baron F, Blaise D, Nagler A, Mohty M. Impact of antithymocyte globulin doses in reduced intensity conditioning before allogeneic transplantation from matched sibling donor for patients with acute myeloid leukemia: a report from the acute leukemia working party of European group of Bone Marrow Transplantation. Bone Marrow Transplant. 2018 Apr;53(4):431-437. doi: 10.1038/s41409-017-0043-y. Epub 2018 Jan 12. — View Citation

Finke J, Schmoor C, Bethge WA, Ottinger HD, Stelljes M, Zander AR, Volin L, Heim DA, Schwerdtfeger R, Kolbe K, Mayer J, Maertens JA, Linkesch W, Holler E, Koza V, Bornhäuser M, Einsele H, Bertz H, Grishina O, Socié G; ATG-Fresenius Trial Group. Prognostic factors affecting outcome after allogeneic transplantation for hematological malignancies from unrelated donors: results from a randomized trial. Biol Blood Marrow Transplant. 2012 Nov;18(11):1716-26. doi: 10.1016/j.bbmt.2012.06.001. Epub 2012 Jun 17. — View Citation

Kanakry CG, Bolaños-Meade J, Kasamon YL, Zahurak M, Durakovic N, Furlong T, Mielcarek M, Medeot M, Gojo I, Smith BD, Kanakry JA, Borrello IM, Brodsky RA, Gladstone DE, Huff CA, Matsui WH, Swinnen LJ, Cooke KR, Ambinder RF, Fuchs EJ, de Lima MJ, Andersson BS, Varadhan R, O'Donnell PV, Jones RJ, Luznik L. Low immunosuppressive burden after HLA-matched related or unrelated BMT using posttransplantation cyclophosphamide. Blood. 2017 Mar 9;129(10):1389-1393. doi: 10.1182/blood-2016-09-737825. Epub 2017 Jan 3. — View Citation

Mehta RS, Saliba RM, Chen J, Rondon G, Hammerstrom AE, Alousi A, Qazilbash M, Bashir Q, Ahmed S, Popat U, Hosing C, Khouri I, Shpall EJ, Champlin RE, Ciurea SO. Post-transplantation cyclophosphamide versus conventional graft-versus-host disease prophylaxis in mismatched unrelated donor haematopoietic cell transplantation. Br J Haematol. 2016 May;173(3):444-55. doi: 10.1111/bjh.13977. Epub 2016 Mar 7. — View Citation

Moiseev IS, Pirogova OV, Alyanski AL, Babenko EV, Gindina TL, Darskaya EI, Slesarchuk OA, Bondarenko SN, Afanasyev BV. Graft-versus-Host Disease Prophylaxis in Unrelated Peripheral Blood Stem Cell Transplantation with Post-Transplantation Cyclophosphamide, Tacrolimus, and Mycophenolate Mofetil. Biol Blood Marrow Transplant. 2016 Jun;22(6):1037-1042. doi: 10.1016/j.bbmt.2016.03.004. Epub 2016 Mar 10. — View Citation

Rashidi A, Slade M, DiPersio JF, Westervelt P, Vij R, Romee R. Post-transplant high-dose cyclophosphamide after HLA-matched vs haploidentical hematopoietic cell transplantation for AML. Bone Marrow Transplant. 2016 Dec;51(12):1561-1564. doi: 10.1038/bmt.2016.217. Epub 2016 Aug 15. — View Citation

Saber W, Opie S, Rizzo JD, Zhang MJ, Horowitz MM, Schriber J. Outcomes after matched unrelated donor versus identical sibling hematopoietic cell transplantation in adults with acute myelogenous leukemia. Blood. 2012 Apr 26;119(17):3908-16. doi: 10.1182/blood-2011-09-381699. Epub 2012 Feb 10. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Graft Failure Incidence	ANC < 500/microL after 42 days after graft infusion	2 years
Other	Time Until Neutrophil Engraftment	Time to ANC > 500/microL for three consecutive days	2 years
Other	Time Until Platelet Engraftment	Time to platelet count > 50,000/microL, without transfusion in the last 7 days	2 years
Other	Immunological Reconstitution	Total lymphocyte count as well as its subsets (CD4, CD8, CD19, CD56)	Days +60, +100 and +180
Other	Days hospitalized	Days admitted to the hospital	First 100 days after graft infusion
Primary	Overall Survival	Time to last follow-up or death	4 years
Secondary	Progression free survival	Time until last follow-up, death or disease relapse	4 years
Secondary	Acute Graft Versus Host Disease	Time until acute GvHD development	4 years
Secondary	Chronic Graft Versus Host Disease	Time until chronic GvHD development	4 years
Secondary	Treatment Related Mortality	Time until death related to HSCT complications	4 years