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

NCT03818334 | Recruiting Phase 2 DMC

• 1 other identifier: SGPP 3549-18
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief 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).

Conditions

Bone Marrow Transplant Complications; Graft Versus Host Disease; Infection Viral; Engraft Failure; Immunologic Suppression

Keywords

Bone Marrow Transplantation; Hematological Malignancies; Post-Cy

Outcome Measures

Primary Outcomes (1)

• Overall Survival

  Time to last follow-up or death

  4 years

Secondary Outcomes (4)

• Progression free survival

  4 years

• Acute Graft Versus Host Disease

  4 years

• Chronic Graft Versus Host Disease

  4 years

• Treatment Related Mortality

  4 years

Other Outcomes (5)

• Graft Failure Incidence

  2 years

• Time Until Neutrophil Engraftment

  2 years

• Time Until Platelet Engraftment

  2 years

Study Arms (2)

Post Cyclophosphamide

EXPERIMENTAL

Cyclophosphamide 50 mg/Kg on days +3 and +4 AND Calcineurin Inhibitor from day +5 AND Mycofenolate Mofetil from day +5 until day +35

Drug: Cyclophosphamide

Thymoglobulin (ATG)

ACTIVE COMPARATOR

Thymoglobulin (ATG) total dose 5 mg/Kg from day -4 until day -1 AND Calcineurin Inhibitor from day +5 AND Methotrexate on days +1, +3, +6 and +11

Drug: ATG

Interventions

Cyclophosphamide DRUG

Cyclophosphamide 1000 mg/flask

Also known as: Cytoxan

Post Cyclophosphamide

ATG DRUG

Antihuman T-Lymphocyte Immune Globulin 25 mg/flask

Also known as: Thymoglobulin

Thymoglobulin (ATG)

Eligibility Criteria

• Age: 1 Year - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Hospital Israelita Albert Einstein: lead

Study Sites (1)

Hospita Israelita Albert Eintein

São Paulo, São Paulo, 05652-900, Brazil

RECRUITING

Related Publications (8)

• 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, Bornhauser M, Einsele H, Bertz H, Grishina O, Socie 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.

  PMID: 22713691 BACKGROUND

• 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. doi: 10.1016/j.bbmt.2005.12.034.

  PMID: 16635791 BACKGROUND

• Devillier R, Labopin M, Chevallier P, Ledoux MP, Socie 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.

  PMID: 29330391 BACKGROUND

• 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.

  PMID: 22327226 BACKGROUND

• 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.

  PMID: 26947769 BACKGROUND

• 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.

  PMID: 27526282 BACKGROUND

• 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.

  PMID: 26970381 BACKGROUND

• Kanakry CG, Bolanos-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.

  PMID: 28049637 BACKGROUND

MeSH Terms

Conditions

Graft vs Host Disease; Virus Diseases; Hematologic Neoplasms

Interventions

Cyclophosphamide; thymoglobulin

Condition Hierarchy (Ancestors)

Immune System Diseases; Infections; Neoplasms by Site; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds

Study Officials

• Andreza A Feitosa Ribeiro, PhD

  Hospital Israelita Albert Einstein

  PRINCIPAL INVESTIGATOR

• Nelson Hamerschlak, PhD

  Hospital Israelita Albert Einstein

  STUDY CHAIR

Central Study Contacts

Andreza A Feitosa Ribeiro

CONTACT

+5511992512523; andreza.ribeiro@einstein.br

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Physician specialist in Hematopoietic Stem Transplantation, Principal Investigator

Study Record Dates

• First Submitted: January 24, 2019
• First Posted: January 28, 2019
• Study Start: November 6, 2018
• Primary Completion: November 1, 2021
• Study Completion (Estimated): November 1, 2026
• Last Updated: February 1, 2019

Record last verified: 2019-01

Locations

BR (1)