ATG/PTCy in Haplo-PBSCT Randomized Controlled,Multi-center
Condition: Myeloid Tumor
Study type: Interventional
Phase: Phase 4

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.
    

Detailed description: 
      Acute graft-versus-host disease (aGvHD) is the most important obstacle of haploidentical
      hematopoietic stem cell transplantation (Haplo-HSCT) for treatment of patients with
      hematologic malignancies. In the last two decades, the results of Haplo-HSCT have been
      conspicuously improved due to effective prophylaxis strategies for aGvHD, such as in vivo T
      cell depletion (TCD) with anti-thymocyte globulin (ATG) or post-transplant cyclophosphamide
      (PTCy).

      The regimens for prophylaxis of GvHD based on rabbit anti-human thymocyte immunoglobin (ATG
      10mg/kg, Thymoglobin®, Genzyme Polyclonals S.A.S) effectively prevented the occurrence of
      grade II-IV aGvHD with an incidence of 33.4%-46%, grade III-IV aGvHD 12%-14.9%, but the
      reactivation incidences of cytomegalovirus (CMV) and EB virus (EBV) were higher due to a
      slower immune reconstitution(2-4). The 100-day CIs of CMV and EBV viremia were 61%-64%and
      over 50%, respectively. Although ATG-based regimens have achieved excellent results, the
      incidences of aGvHD and the post-transplant virus reactivation are still higher, affecting
      the long-term survival of the patients.

      The regimen of PTCy for prevention of GvHD was developed in 1999 by St. Johns Hopkin's group
      in Baltimore (1) and had outstanding results with the CIs of 34% grades II-IV and of 6%
      grades III-IV aGvHD by day 200 in haplo-bone marrow transplantation (Haplo-BMT) (7),
      respectively. The incidences of viral and fungal infection in Haplo-HSCT with PTCy for GvHD
      prophylaxis were much lower than ATG based regimens. Ruggeri A（8）et al retrospectively
      analyzed the effects of different stem cell source (BM vs PBSC) on the transplant results in
      Haplo-HSCT with PTCy. The results showed that BM was associated with a lower incidence of
      grades II-IV and grades III-IV acute GVHD (21% vs 38%, P ≤ .01; and 4% vs 14%, P < .01,
      respectively), which was further confirmed by Bashey A et al' study（9）. These data indicated
      that PTCy regimen don't have the same effects for GvHD prophylaxis with PBSC graft as
      compared with BM graft in Haplo-HSCT.

      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. A prospective, phase II clinical trial (Clinicaltrials.org NCT03395860) was
      performed to evaluate the efficacy with low dose ATG followed by low dose PTCy as GvHD
      prophylaxis.Thirty-two patients diagnosed with hematological malignancies were enrolled in
      this trial. All patients received myeloablative conditioning regimens except for three
      patients. The cumulative incidences (CIs) of grades II-IV and III-IV acute GvHD were 19.4%
      (95% CI, 5.5-33.3%) and 6.9% (95% CI 0-16.3%) by day 100, respectively. The one-year
      probability of relapse was 25.1% (95% CI, 7.3-42.9%). The one-year probabilities of disease
      free-survival (DFS) and overall survival (OS) was 59% (95% CI, 33.3%-84.7%) and 78.4% (95%
      CI, 63%-93.8%), respectively. The CIs of CMV reactivation and EBV reactivation by day 180
      were 37.5% (95% CI, 19.8-55.2%) and 40.6% (95% CI, 22.6-58.6%), respectively. The results
      suggested that low dose ATG with low dose PTCy as GvHD prophylaxis in Haplo-PBSCT had
      promising activity. A prospective randomized trial is required to compare the efficacies of
      this regimen with ATG-based or PTCy-based regiments in Haplo-PBSCT.
    

Intervention name(s): ATG/PTCy; standard ATG; standard PTCy
Intervention type(s): Drug; Drug; Drug
Intervention description(s): low dose Antithymocyte Globulin plus low dose post-transplant cyclophosphamide as graft-versus-host disease prophylaxis in haploidentical peripheral blood stem cell transplantation; in vivo T cell depletion (TCD) with anti-thymocyte globulin (ATG) as graft-versus-host disease prophylaxis in haploidentical peripheral blood stem cell transplantation; post-transplant cyclophosphamide (PTCy) as graft-versus-host disease prophylaxis in haploidentical peripheral blood stem cell
Other intervention name(s): ATG; PTCy
Allocation: Randomized
Intervention model: Single Group Assignment
Intervention model description: ATG+PTCy
Masking: Single (Participant)
Primary purpose: Treatment
Keywords: ATG; PTCy; haplo-PBSCT; GVHD