Malladi wins funding to test new treatment for chronic GvHD
Dr Ram Malladi, working in the Centre for Clinical Haematology, has won funding for a trial of an immunosuppressive drug to treat Graft versus Host Disease (GvHD), a harmful immune reaction that occurs after Stem Cell Transplantation (SCT) treatment for haematological malignancies.
The trial, a Phase II non-randomised study named AZTEC, involves use of the drug Azacytidine in the treatment of patients developing chronic GvHD, and aims to establish both the safety and efficacy of the treatment.
“GvHD is a highly unpleasant and, in many cases, life-threatening side-effect of allogeneic stem cell transplantation. This trial aims to suppress GvHD using a drug that has been shown to increase a particular type of immune cell that damps down immune responses – called T regulatory cells,” commented Dr Malladi.
Previous work from the stem cell transplant group led by Professors Craddock and Moss, has shown that the same drug given immediately after SCT can prevent GvHD, providing hope that it might also work for cases where GvHD persists.
The new study, which is joint funded by the LLR and by Celgene , aims to treat patients who have failed a previous treatment, as Dr Malladi explained. “Normally patients receive steroid drugs to alleviate GvHD, however these often don’t work well. This trial provides a new treatment for such patients – where their GvHD is harder to control. ”
Dr Malladi also highlighted the design of the new trial: “The trial is non-randomised, which means that all patients will receive the new treatment. We will then assess how each patient responds by comparing with patients we have previously treated using the standard treatments currently available, to decide whether the new treatment is a success.”
If the treatment is deemed to be successful, it could be extended to other sets of patients : “Usually the earlier you can intervene to treat a side-effect the better,” commented Dr Malladi, “and if this trial is a success, we will consider testing out this drug on patients when they first present with GvHD, rather than using it when they have failed to respond to steroid treatment.”
Azacitidine augments expansion of regulatory T cells after allogeneic stem cell transplantation in patients with acute myeloid leukemia (AML). Goodyear OC, Dennis M, Jilani NY, Loke J, Siddique S, Ryan G, Nunnick J, Khanum R, Raghavan M, Cook M, Snowden JA, Griffiths M, Russell N, Yin J, Crawley C, Cook G, Vyas P, Moss P, Malladi R, Craddock CF. Blood. 2012 Apr 5;119(14):3361-9.
Induction of a CD8+ T-cell response to the MAGE cancer testis antigen by combined treatment with azacitidine and sodium valproate in patients with acute myeloid leukemia and myelodysplasia. Goodyear O, Agathanggelou A, Novitzky-Basso I, Siddique S, McSkeane T, Ryan G, Vyas P, Cavenagh J, Stankovic T, Moss P, Craddock C. Blood. 2010 Sep 16;116(11):1908-18.
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