Clinical Trial: GVHD Prophylaxis With Post-transplantation Bendamustine in Refractory Leukemia

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

Official Title: Dose-escalation Study of Graft-versus-host Disease Prophylaxis With High-dose Post-transplantation Bendamustine in Patients With Refractory Acute Leukemia

Brief Summary: Our and other groups have demonstrated very low incidence of acute and chronic graft-versus-host disease (GVHD) with post-transplantation cyclophosphamide (PTCy) in haploidentical, unrelated and related allogeneic stem cell transplantation (SCT). Nonetheless for majority of the grafts, except for 10/10 HLA-matched bone marrow, with this type of prophylaxis require concomitant administration of calcineurin inhibitors±MMF, which delays immune reconstitution and development of graft-versus-leukemia (GVL) effect. So, despite reduction of transplant-related mortality, use of PTCy doesn't lead to the reduction of relapse incidence. This is particularly important for relapsed or refractory acute leukemia patients, where, despite all efforts to intensify conditioning regimens, relapses after SCT occur in more than 50% of patients, and long-term survival rarely exceeds 10-20%. In preclinical model of haploidentical SCT the substitution of post-transplantation cyclophosphamide with bendamustine, led to comparable GVHD control, but significantly augmented GVL effect. To test this hypothesis and improve the outcome of allogeneic SCT in refractory acute leukemia patients we initiated a pilot trial with high-dose post-transplantation bendamustine for GVHD prophylaxis. The selection of doses is based on the previous dose-escalation studies. No additional immunosuppression is planned for this trial.

Detailed Summary:
Sponsor: St. Petersburg State Pavlov Medical University

Current Primary Outcome: Engraftment rate [ Time Frame: 60 days ]

Engraftment is defined as the first of 3 consecutive days with an ANC>500 per μl and WBC>1000 per μl. Platelet engraftment is not mandatory for the endpoint.


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Relapse rate analysis [ Time Frame: 365 days ]
  • Non-relapse mortality analysis [ Time Frame: 365 days ]
  • Incidence of acute GVHD, grades II-IV [ Time Frame: 180 days ]
  • Incidence of chronic GVHD, moderate and severe (NIH criteria) [ Time Frame: 365 days ]
  • Overall survival analysis [ Time Frame: 365 days ]
  • Event-free survival analysis [ Time Frame: 365 days ]
  • Toxicity (NCI CTCAE 4.03) [ Time Frame: 100 days ]
    Toxicity parameters based on NCI CTCAE 4.03 grades: hepatotoxicity (liver function tests), nephrotoxicity (creatinine), neurotoxicity (attending physician assessment), mucositis (attending physician assessment), hemorrhagic cystitis (attending physician assessment), cardiotoxicity (ECG, echocardiography). Additional toxicity parameters: incidence and severity of veno-occlusive disease, incidence of transplant-associated microangiopathy
  • Infectious complications, including analysis of severe bacterial, fungal and viral infections incidence [ Time Frame: 100 days ]


Original Secondary Outcome: Same as current

Information By: St. Petersburg State Pavlov Medical University

Dates:
Date Received: June 9, 2016
Date Started: June 2016
Date Completion: June 2019
Last Updated: December 14, 2016
Last Verified: December 2016