Cell Medica, a leading UK cellular therapeutics company that develops, manufactures and markets cellular immunotherapy products for the treatment of infectious disease and cancer, announces that the first patient has been treated in the CMV~ACE/ASPECT trial at University College Hospital London. The Phase II randomised clinical trial is designed to demonstrate the efficacy of adoptive cellular therapy for the pre-emptive treatment of cytomegalovirus (CMV) infections in patients who have received a bone marrow transplant from an unrelated donor.

Adoptive cellular therapy has been shown to prevent viral diseases in patients post allogeneic haematopoietic stem cell (bone marrow) transplant[1,2]. These patients, typically leukaemia or lymphoma patients, have profoundly compromised immune systems and are at high risk of the reactivation of latent CMV infection, often manifesting as interstitial pneumonitis. CMV serostatus continues to be a risk factor which influences the survival outcome of bone marrow transplant patients and improving the treatment of CMV infections represents an important clinical need[3,4]. Patients undergoing bone marrow transplant from an unrelated donor are at particularly high risk of infection and efficacy in this patient group will add significantly to the market potential of the cell therapy.

The trial represents an important collaboration between leading players from industry, the charitable sector, academic research and the National Health Service with the shared aim of establishing adoptive cellular therapy as routine clinical practice for the treatment of patients at high risk of CMV infection following a bone marrow transplant.

Cell Medica is sponsoring the study and providing the majority of the cell therapy products for the patients being treated. Cell Medica is commercialising a proprietary form of the cell therapy referred to as Cytovir CMV.

Leukaemia & Lymphoma Research is a UK charity dedicated to research into blood cancers including leukaemia, lymphoma and myeloma. The charity is funding certain aspects of the trial.

The University of Birmingham is a research-intensive University and haematology expert Professor Paul Moss, Head of Cancer Sciences, has been pioneering the development of cellular immunotherapy.

NHS Blood and Transplant (NHSBT) is a Special Health Authority within the NHS with responsibility for optimising the supply of blood, organs and tissues and raising the quality, effectiveness and efficiency of blood and transplant services. NHSBT is providing the cell therapy products for two of the participating hospitals and analysing blood samples to determine patient responses to the treatment within this trial.

Trial Design

The CMV~ACE/ASPECT is a randomised, controlled study and will include 36 patients across ten UK hospitals. Patients in the trial's treatment arm will receive CMV-specific memory T cells while patients in the control arm will receive only conventional antiviral treatment. The Chief Investigator is Dr. Karl Peggs at the UCL Cancer Institute. The study is expected to be completed by the end of 2012 with results published in 2013.

The CMV~ACE/ASPECT study is being carried out at the following hospitals in the UK, subject to final local approvals: University College London Hospital, Queen Elizabeth Hospital, Birmingham, University Hospitals Bristol, King's College Hospital, Manchester Royal Infirmary, The Christie Hospital Manchester, Nottingham City Hospital, Churchill Hospital Oxford, St James's Institute of Oncology, Leeds, and The Royal Free Hospital.

The trial will complement an ongoing confirmatory (Phase III) study, CMV~IMPACT, which is investigating the use of adoptive cell therapy in bone marrow patients whose donors are siblings. The CMV~IMPACT Study is also sponsored by Cell Medica and funded through a Translation Award from The Wellcome Trust.

Gregg Sando, CEO of Cell Medica, commented:

"Cellular immunotherapy represents a new approach for the treatment of infectious disease. In view of the important patient benefits, we are working towards bringing cellular immunotherapy into routine clinical practice as quickly as possible. We share this commitment with Leukaemia & Lymphoma Research, NHSBT and University of Birmingham and all the participating hospitals and look forward to working together on this exciting clinical trial."

References:

[1] Peggs KS, Thomson K, Samuel E, Dyer G, Armoogum J, Chakraverty R, Pang K, Mackinnon S, Lowdell MW. Directly selected cytomegalovirus-reactive donor T cells confer rapid and safe systemic reconstitution of virus-specific immunity following stem cell transplantation. Clin Infect Dis. 2011 Jan;52(1):49-57.

[2] Peggs KS, Verfuerth S, Pizzey A, Chow SL, Thomson K, Mackinnon S. Cytomegalovirus-specific T cell immunotherapy promotes restoration of durable functional antiviral immunity following allogeneic stem cell transplantation. Clin Infect Dis. 2009 Dec 15;49(12):1851-60.

[3] Kroger N, Zabelina T, Kruger W, Renges H, Stute N, Schrum J, et al. Patient cytomegalovirus seropositivity with or without reactivation is the most important prognostic factor for survival and treatment-related mortality in stem cell transplantation from unrelated donors using pre-transplant in vivo T-cell depletion with anti-thymocyte globulin. British Journal of Haematology. 2001 Jun;113(4):1060-71

[4] Ljungman P, Brand R, Einsele H, Frassoni F, Niederwieser D, Cordonnier C. Donor CMV serologic status and outcome of CMV-seropositive recipients after unrelated donor stem cell transplantation: an EBMT megafile analysis. Blood. 2003; 102:4255-60.

Background to the trial = building on the success of earlier clinical studies

Early-stage clinical trials conducted independently by members of Cell Medica's Scientific Advisory Team and including over 40 patients have demonstrated that adoptive cellular therapy can be used to prevent specific infections in patients following bone marrow transplants. The CMV~ACE/ASPECT study will build on these data to determine the level of immunological benefit in a statistically robust manner. The study will also seek to characterise the pharmaco-economics of treatment with Cytovir CMV.

About T cell immunotherapy for the treatment of CMV infection

T cell immunotherapy involves harnessing the power and precision of the human immune system to treat disease. Extensive academic research in the field of clinical immunology has shown that T cells have the ability to recognise and eliminate infections and have the potential to be used in a safe and efficacious manner as an antiviral treatment. Latent infection of cytomegalovirus (CMV) is estimated in over 50% of all humans and reactivation of the virus is one of the leading causes of potentially life threatening illness in immunosuppressed patients, often manifesting as interstitial pneumonitis. Adoptive T cell immunotherapy is based on the selection of CMV-specific memory T cells from the same donor providing the bone marrow (and hence closely matched with respect to tissue type) and infusion of these cells in the patient to prevent or treat CMV infections following a bone marrow transplant.

Source: Cell Medica