Novuspharma SpA has announced the start of a phase II trial for Pixantrone (BBR 2778) as part of the new BSHAP regimen, in patients with aggressive non-Hodgkin's lymphoma (NHL) who are experiencing their first relapse. The trial is expected to recruit around 75 patients in the US and is designed to evaluate the efficacy of BSHAP as a salvage therapy and assess its safety and utility as an induction regimen before bone marrow transplant.
Chemotherapy regimens that contain anthracyclines (such as the widely used CHOP regimen) are highly effective when used to treat patients with newly diagnosed (front-line) aggressive NHL and they can bring about a cure in around a half of patients. However, the prognosis for patients that relapse from this treatment is not good and bone marrow transplant is the only procedure that offers the hope of a cure at this point (see below). Regimens such as ESHAP are used in these relapsed patients, both as an induction therapy prior to bone marrow transplant and as a salvage therapy in patients who are unable to undergo this procedure. The regimens that are used in relapsed patients, such as ESHAP, do not contain anthracyclines, as anthracyclines are associated with cumulative cardiotoxicity which prevents them being used a second time.
Pixantrone is an investigational drug that is being developed by Novuspharma, in order to improve the cardiac safety of the anthracycline drug class. Clinical and pre-clinical studies suggest that Pixantrone has a greatly improved cardiac safety profile compared to the currently marked anthracyclines and that it can be used safety a second time in patients who have received anthracyclines in front-line therapy. In this trial 80mg/m2 of Pixantrone will be administered in combination with cytarabine, methylprednisolone and cisplatin (the so-called BSHAP regimen) in a 21 day cycle. This is a variation of the ESHAP regimen where Pixantrone replaces etoposide. This alteration is hoped to improved efficacy, based on the high activity of anthracyclines in NHL and the fact that Pixantrone was shown to be highly synergistic with platinum agents, such as cisplatin, in preclinical studies.
The primary endpoint of the trial will be overall response rate. The complete response (CR) rate will also be of particular interest, as patients who achieve a CR with induction therapy have a better chance of successful bone marrow transplant. Furthermore, the trial will have a two arm design, allowing patients eligible for bone marrow transplant to undergo this procedure and be followed as part of the trial. This should allow the safety and utility of using BSHAP as an induction and mobilisation regimen to be assessed, in addition to a further evaluation of BSHAP as a salvage regimen.
After patients have received two cycles of BSHAP, they will be assessed for their suitability to undergo bone marrow transplant and those considered transplant unsuitable may receive up to six cycles of BSHAP in total and will be followed for response and survival data. Those patients experiencing a complete or partial response and considered suitable for transplant, may proceed to stem cell mobilisation with one or more cycles of BSHAP, plus rituximab. If sufficient numbers of bone marrow stem cells are harvested, patients will then receive high dose chemotherapy, followed by a re-infusion of their previously harvested stem cells (see notes to editors). The proportion of patients achieving a successful mobilisation and harvest of bone marrow stem cells will be a secondary endpoint of the trial.