Bendamustine, Cytarabine, Etoposide and Melphalan (BeEAM) as Conditioning for Autologous Stem Cell Transplant (ASCT) in Aggressive Non Hodgkin's Lymphoma (NHL).
Condition: Bendamustine; Conditioning Therapy; Autologous Stem Cell Transplant; Aggressive Non Hodgkin's Lymphoma
MeSH terms: Lymphoma; Lymphoma, Non-Hodgkin; Aggression
Study type: Interventional
Phase: Phase 2

Summary: 
      The purpose of this study is to determine whether Bendamustine in combination with Etoposide,
      Cytarabine and Melphalan (BeEAM) are effective as conditioning followed by ASCT in patients
      with aggressive lymphoma.
    

Detailed description: 
      BCNU (carmustine is a nitrosurea alkylating agent used for many years in the conditioning of
      patients with lymphoma however this drug is hardly available in some countries in Europe,
      moreover to improve conditioning regimens in autologous stem cell transplant is important
      because the anti-tumoral effect of high dose therapy are responsible for this procedure
      efficacy. Although for many years few advances have been achieved in this area now new drugs
      can be tested in these patients.

      Bendamustine is a unique cytotoxic agent with structural similarities to alkylating agents
      and antimetabolites, but which is non-cross-resistant with alkylating agents and other drugs
      in vitro and in the clinic. Early clinical studies conducted in the German Democratic
      Republic more than 30 years ago suggested promising activity in indolent non-Hodgkin's
      lymphoma (NHL). Two North American trials reported responses in more than 70% of patients
      with chemotherapy- and rituximab-refractory disease, suggesting that bendamustine may be the
      most effective drug available for this patient population. Response rates of 90% to 92%, with
      complete remission in 55% to 60%, have been reported in patients with follicular and
      mantle-cell lymphoma with the combination of bendamustine and rituximab.(Cheson 2009) Leone
      et all have recently reported results on the characterization of the mechanisms of action of
      bendamustine and its comparison with structurally related compounds as chlorambucil and
      phosphoramide mustard have demonstrated that bendamustine displays a distinct mechanisms of
      action including activation of DNA-damage stress response and apoptosis, inhibition of
      mitotic checkpoints, and induction of mitotic catastrophe. Also bendamustine activates a base
      excision DNA repair pathway rather than an alkyltransferase DNA repair mechanism.

      These data suggest that bendamustine possesses mechanistic features that differentiate it
      from other alkylating agents and makes this old new drug an attractive one to combine with
      other agents in the conditioning transplant setting (Leone 2008).
    

Intervention name(s): Bendamustine-EAM
Intervention type(s): Drug
Intervention description(s): Bendamustine 200 mg/m2 starting dose on day -7 and -6 Etoposide 200 mg/m2 from day -5 to day -2 Ara-C 400 mg/m2 from day -5 to day -2 Melphalan 140 mg/m2 on day -1
Intervention MeSH terms: Bendamustine Hydrochloride
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Bendamustine; Conditioning Therapy; Autologous Stem Cell Transplant; Aggressive Non Hodgkin's Lymphoma