Clinical Trial: Fludarabine Based RIC for Bone Marrow Failure Syndromes

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: Fludarabine-Based Conditioning for Matched Related Donor Bone Marrow Transplantation in Patients With Bone Marrow Failure Syndromes

Brief Summary: This is a pilot study to determine whether fludarabine-based reduced intensity conditioning (RIC) regimens facilitate successful donor engraftment of patients with acquired aplastic anemia (AA) and Inherited bone marrow failure (iBMF) syndromes undergoing Matched related donor bone marrow transplant (MRD-BMT).

Detailed Summary: Acquired AA patients will receive the experimental regimen of fludarabine with dose-reduced cyclophosphamide, with results in this prospective single arm experimental group evaluated in the context of our institutional historical experience using HD Cy regimens as well as published outcomes using both fludarabine and high-dose cyclophosphamide-based regimens for MRD-BMT in aplastic anemia. iBMF syndrome patients will receive one of two fludarabine-containing regimens based on disease characteristics, and our outcomes will be compared to previously published data using a variety of regimens. Graft versus host disease (GvHD) prophylaxis will consist of cyclosporine/tacrolimus alone for patients with acquired AA or cyclosporine/tacrolimus plus mycophenolate for patients with iBMF syndromes. For both acquired AA and iBMF syndrome patients, donor chimerism will be assessed at scheduled intervals following BMT and will be used to define patients with full donor or mixed chimerism for comparisons of survival, graft failure, cytogenetic, GvHD, and immune reconstitution outcomes.
Sponsor: Children's Hospital of Philadelphia

Current Primary Outcome:

• Rate of graft failure [ Time Frame: Up to 1 year post transplant ]
  Combined rate of primary and secondary graft failure. Primary graft failure is defined as no evidence of neutrophil engraftment by day +28 after stem cell infusion. Secondary graft failure is defined as an ANC<100 for >7-10 days after initial engraftment occurs and is confirmed by hypocellular bone marrow biopsy and donor engraftment <20%.
• Time to neutrophil engraftment [ Time Frame: Up to 1 year post transplant ]
  The time from the day of transplant until neutrophil engraftment, which is defined as the first day of ANC >500/ul for the first of 3 consecutive days.
• Transplant-related mortality [ Time Frame: Up to 100 days post transplant ]

Original Primary Outcome: Time to neutrophil engraftment [ Time Frame: Up to 1 year post transplant ]

Current Secondary Outcome:

• Rate of overall survival [ Time Frame: Up to 1 year post transplant ]
• Rate of disease free survival [ Time Frame: Up to 1 year post transplant ]

Original Secondary Outcome:

• Rate of overall survival [ Time Frame: Up to 1 year post transplant ]
  To determine the rate of overall survival with stable donor engraftment at one year for patients with defined iBMF syndromes receiving MRD-BMT with fludarabine-based, disease-specific conditioning.
• Time to stable engraftment [ Time Frame: Up to 1 year post transplant ]
  The time from the day of transplant until stable engraftment which is defined as donor chimerism >20% following initial neutrophil engraftment
• Incidence of primary graft failure [ Time Frame: Up to 28 days after transplant ]
  Primary graft failure is defined as no evidence of neutrophil engraftment by day +28 after stem cell infusion
• Incidence of secondary graft failure [ Time Frame: Up to 1 year post transplant ]
  Secondary graft failure is defined as an ANC<100 for >7-10 days after initial engraftment occurs and is confirmed by hypocellular bone marrow biopsy and donor engraftment <20%

Information By: Children's Hospital of Philadelphia

Dates:
Date Received: October 7, 2016
Date Started: April 2015
Date Completion: April 2020
Last Updated: October 27, 2016
Last Verified: October 2016