Leukemia Insights - Winter 2010
Acute Promyelocytic Leukemia
Tamibarotene is a synthetic retinoid that has been shown to be well-tolerated and effective in both the newly diagnosed and relapsed/refractory APL populations in studies in Japan. In April 2005, tamibarotene received regulatory approval in Japan for use in relapsed/refractory APL following the successful completion of two Phase II studies. We are conducting a study looking at the benefits of this agent in patients with APL relapsing from prior ATRA and ATO. Early results are very encouraging with patients achieving a second complete remission.
- 2007-0512, Phase II oral Tamibarotene in relapsed APL
Other Salvage Regimens
The outcome of patients with relapsed AML is guarded; current strategies are based on achieving a second CR and proceeding to an allogeneic stem 4 cell transplant, if available. For patients with primary refractory disease or those who relapse a short time (generally less than a year) after achieving a CR, the prognosis is especially poor. A number of investigational approaches such as epigenetic modification with hypomethylating agents and histone deacetylase inhibitors, use of FLT3 tyrosine kinase inhibitors, inhibitors of other signaling pathways (such as JAK-STAT and RAF/ERK/MEK/MAPK), use of aminopeptidase inhibitor tosedostat, as well as new cytotoxic agents and new formulations of traditional cytotoxic agents are under investigation.
The prognosis for patients who relapse after a longer first CR is better as they are generally more likely to respond to regimens similar to their original treatment. Combinations of cytarabine with clofarabine and idarubicin, or with new topoisomerase inhibitors are under investigation. A new liposomal formulation of cytarabine and daunorubicin with better intracellular delivery is also under investigation.
- 2008-0679, Phase II CPX-351 vs. standard salvage for first relapse (18-65)
- 2010-0692, Phase III Cytarabine ± Vosaroxin for primary refractory or first relapse (≥ 18) [pending]
- 2008-0501, Phase I Sorafenib + Plerixafor +GCSF (FLT3-ITD+)(≥ 18)
- 2010-0511, Phase II Sorafenib + azacytidine [pending]
- 2009-0560, Phase II AC220 (FLT3-ITD+)(≥ 18)
- 2009-0187, Phase II tosedostat (≥ 60)
- 2009-0781, Phase II twice daily fludarabine + cytarabine ± TKI (Sorafenib, dasatinib, imatinib or nilotinib depending on the underlying disease) (≥18)
Additionally, improvements in supportive care measures such as infection prophylaxis and treatment, also under study at MDACC, may contribute to a better outcome in relapsed patients. We are currently examining the benefit from white blood cell transfusions in the setting of neutropenic fever/infections.
- 2007-0797, A prospective, randomized study of irradiated vs. non-irradiated WBC transfusions for patients with severe neutropenia and documented infections
- 2010-0468, A prospective, randomized study of prophylactic vs. therapeutic WBC transfusions A number of phase I and II studies of investigational agents or combinations are also available for patients with more advanced disease.
- 2009-0239, Phase I GSK1120212 (MEK inhibitor) in patients with RAS mutated AML
- 2009-0195, Phase I/II MSC1936369 (MEK inhibitor)
- 2007-0925, Phase II INCB018424 (JAK2 inhibitor)
- 2010-0243, Phase II MK-2206 (AKT inhibitor)
- 2008-0313, Phase I DT-IL3 (immunotoxin)
- 2009-0772, Phase I PR104 (hypoxia-activated prodrug)
- 2010-0078, Phase I PF04449913 (Hedgehog inhibitor)
- 2009-1000, Phase I 4-Thio-araC
- 2009-0752, Phase I Belinostat + bortezomib
- 2009-0788, Phase I ABT348 (Aurora kinase inhibitor)
- 2003-0578, Phase I L-Grb2 antisense oligonucleotide
- 2007-0488, Phase I OPB-31121 (Stat3 inhibitor)
- 2010-0244, Phase I TG02 (CDK inhibitor)
- 2009-0785, Phase I LY2523355 (Eg5 inhibitor)
- 2009-0196, Phase I SAR103168 (Multi-kinase inhibitor)
- 2009-0467, Phase I Azacytidine + lenalidomide
- 2010-0303, Phase I ON01910.Na (Multi-kinase inhibitor)
- 2010-0268, Phase I TH302 (hypoxia-activated prodrug)
- 2008-0786, Phase I IPI-493 (Hsp90 inhibitor)
For information about these or any Leukemia protocol, please call Dr. Farhad Ravandi or any Leukemia physician.