No blogging yesterday as I was at the UK CLL group's clinical trials meeting. This was a good chance to review what was happening in the UK. Currently we are without a major change. LRF CLL4 has been analyzed and published with its concusion that the combination of fludarabine and cyclphosphamide gives more responses and longer remissions than either fludarabine of chlorambucil as single agents, and rather more surprisingly that these two drugs cannot be distinguished by their performance. However, none of these drugs gives a longer overall survival compared to the others when used as first line treatment. There are 5 of 6 other spin-off papers due from that trial, mainly about the prognostic factors, but also about the comparison of oral and iv fludarabine.
The next trial has been a long time in coming because the Germans have rather stolen a march on us, and have already asked the next major question, which is does the addition of ritiuximab improve results. Although this will be the subject of a major paper at ASH, we know from heavy hints from the Roche website that the answer will be a very high response rate (perhaps 95%) much longer remissions (4-5 years?) and no improvement in overall survival.
So what is there left to do with conventional drugs? There is the Ron Taylor question: do we need such large doses of rituximab? And there is the Spanish question: is there a place for mitoxantrone?
Our next trial is going to address these, starting, we hope, early next year. The randomization will be between FCR and FCMr. F=Fludarabine, C=Cyclophosphamide, M=mitoxantrone (at a small dose, 6mg/sq m), R=full dose rituximab, r=minidose rituximab (100mg). At the same time we will conduct a randomized phase II study comparing FCR with FCMR.
We currently have a randomized phase II study looking at chlorambucil versus chlorambucil plus rituximab in patients though unfit for fludarabine and are looking at a randomized phase III study looking at chlorambucil with or without ofatumumab.
Several centers are also taking part in the international study comparing FCR with FCR plus lumiliximab.
The consolidation study with Campath is continuing but is recruiting poorly perhaps because of the 6 dearths in the American study. It is clear that eradication of minimal residual disease should only be undertaken in centres experienced with the problem.
The 17p- trial (Campred) is almost complete and it is touch and go whether it will be ready for ASH. A new trial adding Revlimid is being designed. Revlimid is also the drug of choice for early stage, poor risk patients.
On the horizon are some Treanda trials: R-Bendamustine v R-chlorambucil might be attractive as long as they chose a proper dose of chlorambucil. An SMZL comparing splenectomy and FR might have difficulty recruiting even if it were pan-Europe. We might join the CALGB mini-allo trial.