Post Transplant Cyclophosphamide in Matched Unrelated Donor Stem Cell Transplantation for Hematological Malignancies
Primary Purpose
Bone Marrow Transplant Complications, Graft Versus Host Disease, Infection Viral
Status
Recruiting
Phase
Phase 2
Locations
Brazil
Study Type
Interventional
Intervention
Cyclophosphamide
ATG
Sponsored by
About this trial
This is an interventional prevention trial for Bone Marrow Transplant Complications focused on measuring Bone Marrow Transplantation, Hematological Malignancies, Post-Cy
Eligibility Criteria
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
Sites / Locations
- Hospita Israelita Albert EinteinRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
Post Cyclophosphamide
Thymoglobulin (ATG)
Arm Description
Cyclophosphamide 50 mg/Kg on days +3 and +4 AND Calcineurin Inhibitor from day +5 AND Mycofenolate Mofetil from day +5 until day +35
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
Outcomes
Primary Outcome Measures
Overall Survival
Time to last follow-up or death
Secondary Outcome Measures
Progression free survival
Time until last follow-up, death or disease relapse
Acute Graft Versus Host Disease
Time until acute GvHD development
Chronic Graft Versus Host Disease
Time until chronic GvHD development
Treatment Related Mortality
Time until death related to HSCT complications
Full Information
NCT ID
NCT03818334
First Posted
January 24, 2019
Last Updated
January 31, 2019
Sponsor
Hospital Israelita Albert Einstein
1. Study Identification
Unique Protocol Identification Number
NCT03818334
Brief Title
Post Transplant Cyclophosphamide in Matched Unrelated Donor Stem Cell Transplantation for Hematological Malignancies
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
Study Type
Interventional
2. Study Status
Record Verification Date
January 2019
Overall Recruitment Status
Recruiting
Study Start Date
November 6, 2018 (Actual)
Primary Completion Date
November 1, 2021 (Anticipated)
Study Completion Date
November 1, 2026 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Hospital Israelita Albert Einstein
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
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).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Bone Marrow Transplant Complications, Graft Versus Host Disease, Infection Viral, Engraft Failure, Immunologic Suppression
Keywords
Bone Marrow Transplantation, Hematological Malignancies, Post-Cy
7. Study Design
Primary Purpose
Prevention
Study Phase
Phase 2, Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
50 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Post Cyclophosphamide
Arm Type
Experimental
Arm Description
Cyclophosphamide 50 mg/Kg on days +3 and +4 AND Calcineurin Inhibitor from day +5 AND Mycofenolate Mofetil from day +5 until day +35
Arm Title
Thymoglobulin (ATG)
Arm Type
Active Comparator
Arm Description
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
Intervention Type
Drug
Intervention Name(s)
Cyclophosphamide
Other Intervention Name(s)
Cytoxan
Intervention Description
Cyclophosphamide 1000 mg/flask
Intervention Type
Drug
Intervention Name(s)
ATG
Other Intervention Name(s)
Thymoglobulin
Intervention Description
Antihuman T-Lymphocyte Immune Globulin 25 mg/flask
Primary Outcome Measure Information:
Title
Overall Survival
Description
Time to last follow-up or death
Time Frame
4 years
Secondary Outcome Measure Information:
Title
Progression free survival
Description
Time until last follow-up, death or disease relapse
Time Frame
4 years
Title
Acute Graft Versus Host Disease
Description
Time until acute GvHD development
Time Frame
4 years
Title
Chronic Graft Versus Host Disease
Description
Time until chronic GvHD development
Time Frame
4 years
Title
Treatment Related Mortality
Description
Time until death related to HSCT complications
Time Frame
4 years
Other Pre-specified Outcome Measures:
Title
Graft Failure Incidence
Description
ANC < 500/microL after 42 days after graft infusion
Time Frame
2 years
Title
Time Until Neutrophil Engraftment
Description
Time to ANC > 500/microL for three consecutive days
Time Frame
2 years
Title
Time Until Platelet Engraftment
Description
Time to platelet count > 50,000/microL, without transfusion in the last 7 days
Time Frame
2 years
Title
Immunological Reconstitution
Description
Total lymphocyte count as well as its subsets (CD4, CD8, CD19, CD56)
Time Frame
Days +60, +100 and +180
Title
Days hospitalized
Description
Days admitted to the hospital
Time Frame
First 100 days after graft infusion
10. Eligibility
Sex
All
Minimum Age & Unit of Time
1 Year
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Andreza A Feitosa Ribeiro
Phone
+5511992512523
Email
andreza.ribeiro@einstein.br
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Andreza A Feitosa Ribeiro, PhD
Organizational Affiliation
Hospital Israelita Albert Einstein
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Nelson Hamerschlak, PhD
Organizational Affiliation
Hospital Israelita Albert Einstein
Official's Role
Study Chair
Facility Information:
Facility Name
Hospita Israelita Albert Eintein
City
São Paulo
State/Province
SP
ZIP/Postal Code
05652-900
Country
Brazil
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Mirele Santos
Phone
+112151-0305
Email
mirele.santos@einstein.br
12. IPD Sharing Statement
Plan to Share IPD
Undecided
Citations:
PubMed Identifier
22713691
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, 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.
Results Reference
background
PubMed Identifier
16635791
Citation
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.
Results Reference
background
PubMed Identifier
29330391
Citation
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.
Results Reference
background
PubMed Identifier
22327226
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.
Results Reference
background
PubMed Identifier
26947769
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.
Results Reference
background
PubMed Identifier
27526282
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.
Results Reference
background
PubMed Identifier
26970381
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.
Results Reference
background
PubMed Identifier
28049637
Citation
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.
Results Reference
background
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Post Transplant Cyclophosphamide in Matched Unrelated Donor Stem Cell Transplantation for Hematological Malignancies
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