Clinical Trial: Comparison of Cy-Atg vs Flu-Atg for the Conditioning Therapy in Allo-HCT for Adult Aplastic Anemia

Study Status: Completed
Recruit Status: Unknown status
Study Type: Interventional

Official Title: Randomized Comparison of Cyclophosphamide Versus Fludarabine in Addition to Anti-thymocyte Globulin for the Conditioning Therapy in Allogeneic Hematopoietic Cell Transplantation for Adult Acquired

Brief Summary:

The purpose of this study is to reduce the regimen related toxicities and transplantation related mortality after allogeneic stem cell transplantation in adult acquired aplastic anemia (AA), the trials of reduced dose of Cy along with fludarabine and ATG were performed.11-21 The investigators preliminary data of randomized comparison of cyclophosphamide plus fludarabine versus cyclophosphamide alone in addition to anti-thymocyte globulin for the conditioning therapy in allogeneic hematopoietic cell transplantation for bone marrow failure syndrome supports reduced dose of Cy along with fludarabine and ATG.

Conditioning regimen without Cy may reduce RRT because Cy-containing conditioning remains several RRT such as hemorrhagic cystitis, SOS and graft versus host disease (GvHD). Recently there were small trials of fludarabine and ATG (Flu-ATG) for the conditioning regimen of alloHSCT.22-24 These data raised the feasibility of fludarabine and ATG without Cy for patients with AA.

This new conditioning regimen of Flu-ATG will be compared to standard regimen of Cy- ATG in a randomized controlled trial.


Detailed Summary:

TREATMENT PLAN

  • The patients will be admitted to laminar air flow room.
  • The patients will have triple lumen Hickman central venous catheter (CVC) placed. Chest X-ray should be taken after CVC placement to confirm the location of CVC and absence of pneumothorax.

  • Menstruating women will be given norethindrone (Primolut) 10 mg po daily.

    1. The preparatory regimen is as follows:

      Conditioning therapy will start on day -5 in patients who are randomized to receive Cy+ATG. Hydration with 0.45% NaCl at 6 liters/24 hours will be started on day -5. Cy 50 mg/kg in D5W 200 ml i.v. over 1-2 hours on days -5 to -2 by pump through a central venous catheter. Mesna 12 mg/kg iv push immediately before Cy and 3, 6, 9, and 12 hours after Cy. Thymoglobuline 3 mg/kg in N/S 500-800 mL (less than 0.5 mg/mL) or lymphoglobuline 15 mg/kg in N/S 500-800 mL (less than 2 mg/mL) iv daily at 8 am on days -4 to -2. Premedication for ATG (ALG) will include methylprednisolone 2 mg/kg iv infusion, Tylenol 600 mg po, and Avil 45.5 mg iv push. The doses of cyclophosphamide and ATG (ALG) will be calculated using actual body weight.

      Conditioning therapy will start on day -7 in patients who are randomized to receive Flu-ATG. Fludarabine 30 mg/m2 will be infused intravenously over 30 minutes in D5W 100 ml for 6 consecutive days (days -7 to -2). Thymoglobuline 3 mg/kg in N/S 500-800 mL (less than 0.5 mg/mL) or lymphoglobuline 15 mg/kg in N/S 500-800 mL (less than 2 mg/mL) iv daily at 8 am on days -4 to -2. Premedication for ATG (ALG) will include m
      Sponsor: Cooperative Study Group A for Hematology

      Current Primary Outcome: regimen-related toxicities(RRT) [ Time Frame: 7 years ]

      • The RRTs will be evaluated in terms of mucositis, hemorrhagic cystitis, SOS, acute graft versus host disease (GvHD), infection rate, graft failure, time to engraftment.
      • Overall feasibility will be evaluated by RRTs, time to engraftment, chronic GvHD, treatment-related mortality (TRM), relapse rate, infertility, chimerism status, changes of hemostatic variables, event-free survival and overall survival.


      Original Primary Outcome: Same as current

      Current Secondary Outcome: Overall feasibility [ Time Frame: 7 years ]

      Day 100 mortality rate, overall survival


      Original Secondary Outcome:

      Information By: Cooperative Study Group A for Hematology

      Dates:
      Date Received: May 19, 2010
      Date Started: March 2010
      Date Completion: February 2016
      Last Updated: September 6, 2012
      Last Verified: September 2012