ATG/PTCy in Haplo-PBSCT Randomized Controlled,Multi-center

NCT03608059 | Completed Phase 4 DMC

• 1 other identifier: SHSYXY-ATG/PTCy multi-center
• Study Type: interventional
• Target: 418
• Locations: 1 country
• Sites: 6

Brief Summary

A novel regimen, which is composed of a low dose of ATG (5 mg/kg) and low-dose PTCy (one dose of PTCy, 50mg/kg) for GvHD prophylaxis in Haplo-PBSCT for patients with hematologic malignancies, was designed to decrease the risk of aGvHD and lower the incidence of virus reactivation.

Conditions

Myeloid Tumor

Keywords

ATG; PTCy; haplo-PBSCT; GVHD

Outcome Measures

Primary Outcomes (1)

• The cumulative incidences of acute GVHD

  The cumulative incidences of aGvHD was defined as the number and the ratio of the participants with aGVHD

  100 days after transplantation

Secondary Outcomes (8)

• Leukocyte engraftment

  1 month

• Platelet engraftment

  1 month

• Donor chimerism

  2 years

• Relapse incidence (RI)

  2 YEARS]

• chronic GVHD

  2 years

Study Arms (3)

ATG/PTCy

EXPERIMENTAL

The GvHD prophylaxis consisted of ATG 2.5mg/kg administered on day -2 to -1 and cyclophosphamide (Cy) 50 mg/kg on day +3, cyclosporine A (CsA) and mycophenolate mofetil (MMF) initiating on day +4. CsA was prescribed at 2 mg/kg as a continuous infusion. The CsA doses were modified to obtain nadir serum levels between 200 and 300 ng/ml. MMF was administered at 15 mg/kg oral 3 times per day (maximum dose 3g per day) until day +34 and was then stopped if no aGvHD. Mycophenolate Sodium Enteric-coated Tablets (MPA) can be used instead of MMF, one tablet MPA corresponds to one tablet MMF. CsA was tapered from day +90 to day +180.

Drug: ATG/PTCy

standard ATG

ACTIVE COMPARATOR

The GvHD prophylaxis consisted of ATG 2.5mg/kg administered on day -4 to -1 , cyclosporine A (CsA) initiating on day -5 and mycophenolate mofetil (MMF) initiating on day +1 . CsA was prescribed at 2 mg/kg as a continuous infusion. The CsA doses were modified to obtain nadir serum levels between 200 and 300 ng/ml. MMF was administered at 15 mg/kg oral 2 times per day (maximum dose 2g per day) until day +30 and was then stopped if no aGvHD. Mycophenolate Sodium Enteric-coated Tablets (MPA) can be used instead of MMF, one tablet MPA corresponds to one tablet MMF. CsA was tapered from day +90 to day +180.

Drug: standard ATG

standard PTCy

ACTIVE COMPARATOR

The GvHD prophylaxis consisted of cyclophosphamide (Cy) 50 mg/kg on day +3, +4,cyclosporine A (CsA) and mycophenolate mofetil (MMF) initiating on day +5. CsA was prescribed at 2 mg/kg as a continuous infusion. The CsA doses were modified to obtain nadir serum levels between 200 and 300 ng/ml. MMF was administered at 15 mg/kg oral 3 times per day (maximum dose 3g per day) until day +35 and was then stopped if no aGvHD. Mycophenolate Sodium Enteric-coated Tablets (MPA) can be used instead of MMF, one tablet MPA corresponds to one tablet MMF. CsA was tapered from day +90 to day +180.

Drug: standard PTCy

Interventions

ATG/PTCy DRUG

low dose Antithymocyte Globulin plus low dose post-transplant cyclophosphamide as graft-versus-host disease prophylaxis in haploidentical peripheral blood stem cell transplantation

ATG/PTCy

standard ATG DRUG

in vivo T cell depletion (TCD) with anti-thymocyte globulin (ATG) as graft-versus-host disease prophylaxis in haploidentical peripheral blood stem cell transplantation

Also known as: ATG

standard ATG

standard PTCy DRUG

post-transplant cyclophosphamide (PTCy) as graft-versus-host disease prophylaxis in haploidentical peripheral blood stem cell

Also known as: PTCy

standard PTCy

Eligibility Criteria

• Age: 14 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Clinical diagnosis of hematologic malignancies (AML CR/blast cell≤20% high-risk MDS) were enrolled in this study. Diagnosis was according to the criteria of 2008 World Health Organization (WHO) classification of myeloid tumors.
• Family members selected as donors were typed at the HLA-A, -B, -DQB1, -C and -DRB1 locus at high-resolution level. Haplotype was defined as recipient-donor number of HLA mismatches \> 3.
• to 70 years old. 4.Performance status scores no more than 2 (ECOG criteria). 5.Adequate organ function as defined by the following criteria: alanine transaminase （ALT）, aspartate transaminase（AST） and total serum bilirubin \<2×ULN (upper limit of normal). Serum creatinine and blood urea nitrogen (BUN) \<1.25×ULN.
• Adequate cardiac function without acute myocardial infarction, arrhythmia or atrioventricular block, heart failure, active rheumatic heart disease and cardiac dilatation(the patients has been improved after treatment of the disease and are not expected to affect transplant can include in the study).
• Absence of any other contraindications of stem cell transplantation. Willingness and ability to perform HSCT.
• Signed and dated informed consent document indicating that the patient (or legally acceptable representative) has been informed of all pertinent aspects of the trial prior to enrollment. Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures.

You may not qualify if:

• DSA strong positive (titer \>10000MFI)
• Life expectancy \< 3 months because of other severe diseases.
• Presence of any fatal disease, including respiratory failure, heart failure, liver or kidney function failure.
• Uncontrolled infection.
• Pregnancy or breastfeeding.
• Has enrolled in another clinical trials.
• Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or study drug administration, or may interfere with the interpretation of study results, and in the judgment of the investigator would make the patient inappropriate for entry into this study.

Sponsors & Collaborators

• Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine: lead

Study Sites (6)

General Hospital of Jinan Military Command.

Qinan, Shandong, China

Location

Shanghai Ruijin Hospital, affiliated with the Medical School of Shanghai Jiaotong University,

Shanghai, Shanghai Municipality, 200002, China

Location

Changhai Hospital

Shanghai, Shanghai Municipality, 200080, China

Location

Xianmin Song

Shanghai, Shanghai Municipality, 200080, China

Location

Shanghai Xinghua Hospital, affiliated with the Medical School of Shanghai Jiaotong University,

Shanghai, Shanghai Municipality, China

Location

Shanghai tongji hospital

Shanghai, China

Location

Related Publications (13)

• Luznik L, Jalla S, Engstrom LW, Iannone R, Fuchs EJ. Durable engraftment of major histocompatibility complex-incompatible cells after nonmyeloablative conditioning with fludarabine, low-dose total body irradiation, and posttransplantation cyclophosphamide. Blood. 2001 Dec 1;98(12):3456-64. doi: 10.1182/blood.v98.12.3456.

  PMID: 11719388 BACKGROUND

• Wang Y, Liu DH, Liu KY, Xu LP, Zhang XH, Han W, Chen H, Chen YH, Wang FR, Wang JZ, Sun YQ, Huang XJ. Long-term follow-up of haploidentical hematopoietic stem cell transplantation without in vitro T cell depletion for the treatment of leukemia: nine years of experience at a single center. Cancer. 2013 Mar 1;119(5):978-85. doi: 10.1002/cncr.27761. Epub 2012 Oct 23.

  PMID: 23097265 BACKGROUND

• Wang Y, Chang YJ, Xu LP, Liu KY, Liu DH, Zhang XH, Chen H, Han W, Chen YH, Wang FR, Wang JZ, Chen Y, Yan CH, Huo MR, Li D, Huang XJ. Who is the best donor for a related HLA haplotype-mismatched transplant? Blood. 2014 Aug 7;124(6):843-50. doi: 10.1182/blood-2014-03-563130. Epub 2014 Jun 10.

  PMID: 24916508 BACKGROUND

• Liu Q, Xuan L, Liu H, Huang F, Zhou H, Fan Z, Zhao K, Wu M, Xu L, Zhai X, Zhang F, Liu C, Sun J, Huang X. Molecular monitoring and stepwise preemptive therapy for Epstein-Barr virus viremia after allogeneic stem cell transplantation. Am J Hematol. 2013 Jul;88(7):550-5. doi: 10.1002/ajh.23452. Epub 2013 May 30.

  PMID: 23564232 BACKGROUND

• Tischer J, Engel N, Fritsch S, Prevalsek D, Hubmann M, Schulz C, Zoellner AK, Bucklein V, Reibke R, Mumm F, Rieger CT, Hill W, Ledderose G, Stemmler HJ, Kohnke T, Jager G, Kolb HJ, Schmid C, Moosmann A, Hausmann A. Virus infection in HLA-haploidentical hematopoietic stem cell transplantation: incidence in the context of immune recovery in two different transplantation settings. Ann Hematol. 2015 Oct;94(10):1677-88. doi: 10.1007/s00277-015-2423-y. Epub 2015 Jun 10.

  PMID: 26055139 BACKGROUND

• 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.

  PMID: 18489989 BACKGROUND

• Ruggeri A, Labopin M, Bacigalupo A, Gulbas Z, Koc Y, Blaise D, Bruno B, Irrera G, Tischer J, Diez-Martin JL, Castagna L, Ciceri F, Mohty M, Nagler A. Bone marrow versus mobilized peripheral blood stem cells in haploidentical transplants using posttransplantation cyclophosphamide. Cancer. 2018 Apr 1;124(7):1428-1437. doi: 10.1002/cncr.31228. Epub 2018 Jan 23.

  PMID: 29360162 BACKGROUND

• Bashey A, Zhang MJ, McCurdy SR, St Martin A, Argall T, Anasetti C, Ciurea SO, Fasan O, Gaballa S, Hamadani M, Munshi P, Al Malki MM, Nakamura R, O'Donnell PV, Perales MA, Raj K, Romee R, Rowley S, Rocha V, Salit RB, Solh M, Soiffer RJ, Fuchs EJ, Eapen M. Mobilized Peripheral Blood Stem Cells Versus Unstimulated Bone Marrow As a Graft Source for T-Cell-Replete Haploidentical Donor Transplantation Using Post-Transplant Cyclophosphamide. J Clin Oncol. 2017 Sep 10;35(26):3002-3009. doi: 10.1200/JCO.2017.72.8428. Epub 2017 Jun 23.

  PMID: 28644773 BACKGROUND

• O'Donnell PV, Luznik L, Jones RJ, Vogelsang GB, Leffell MS, Phelps M, Rhubart P, Cowan K, Piantados S, Fuchs EJ. Nonmyeloablative bone marrow transplantation from partially HLA-mismatched related donors using posttransplantation cyclophosphamide. Biol Blood Marrow Transplant. 2002;8(7):377-86. doi: 10.1053/bbmt.2002.v8.pm12171484.

  PMID: 12171484 BACKGROUND

• Brunstein CG, Gutman JA, Weisdorf DJ, Woolfrey AE, Defor TE, Gooley TA, Verneris MR, Appelbaum FR, Wagner JE, Delaney C. Allogeneic hematopoietic cell transplantation for hematologic malignancy: relative risks and benefits of double umbilical cord blood. Blood. 2010 Nov 25;116(22):4693-9. doi: 10.1182/blood-2010-05-285304. Epub 2010 Aug 4.

  PMID: 20686119 BACKGROUND

• Chen J, Wang RX, Chen F, Sun AN, Qiu HY, Jin ZM, Tang XW, Han Y, Fu ZZ, He GS, Miao M, Ma X, Wu DP. Combination of a haploidentical SCT with an unrelated cord blood unit: a single-arm prospective study. Bone Marrow Transplant. 2014 Feb;49(2):206-11. doi: 10.1038/bmt.2013.154. Epub 2013 Oct 21.

  PMID: 24141650 BACKGROUND

• Przepiorka D, Weisdorf D, Martin P, Klingemann HG, Beatty P, Hows J, Thomas ED. 1994 Consensus Conference on Acute GVHD Grading. Bone Marrow Transplant. 1995 Jun;15(6):825-8.

  PMID: 7581076 BACKGROUND

• Martin PJ, Lee SJ, Przepiorka D, Horowitz MM, Koreth J, Vogelsang GB, Walker I, Carpenter PA, Griffith LM, Akpek G, Mohty M, Wolff D, Pavletic SZ, Cutler CS. National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease: VI. The 2014 Clinical Trial Design Working Group Report. Biol Blood Marrow Transplant. 2015 Aug;21(8):1343-59. doi: 10.1016/j.bbmt.2015.05.004. Epub 2015 May 15.

  PMID: 25985921 BACKGROUND

Study Officials

• xinpeng wang

  Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: ATG+PTCy

Study Record Dates

• First Submitted: July 28, 2018
• First Posted: July 31, 2018
• Study Start: July 28, 2018
• Primary Completion: August 23, 2023
• Study Completion: August 23, 2023
• Last Updated: October 5, 2023

Record last verified: 2023-10

Data Sharing

• IPD Sharing: Will not share

Locations

CN (6)