Our clinical trials unit continues to grow with a wide portfolio of trials covering both malignant and non-malignant haematology. We lead early phase clinical trials through to randomised controlled studies. We currently lead a diverse range of clinical trials in haematologic malignancies, including multiple myeloma, non-Hodgkin lymphoma, acute lymphoblastic leukaemia, acute myeloid leukaemia and myeloproliferative neoplasms. In addition we perform clinical trials for red cell disorders, haemophilia and thrombosis.

Professor Ho has continued to lead the RPA clinical trials unit and attract the most promising trials for our patients with Multiple Myeloma. We have been a major recruiting site for the PERSEUS study which is defining the new state-of-the-art induction therapy for Multiple Myeloma, by incorporating antibody therapy up-front into a potent induction combination. For patients with relapsed Myeloma we have trialled a new monoclonal antibody therapy (Belantamab-Mafodotin) in combination with Bortezomib (DREAMM7 study), and a new oral anti-Myeloma agent with high activity (CC-92480). 

One of the most exciting developments in Myeloma has the development of a potent BCMA-targeted CAR-T, named Ciltacaptagene. This agent has shown extremely high activity in patients with multiply relapsed Myeloma and no available therapeutic options (CARTITUDE2). We have trialled this agent earlier in the disease course of Multiple Myeloma patients, after 1-3 prior lines of therapy, in a phase three randomised trial (CARTITUDE4). This trial is ongoing but has completed recruitment and is likely to define a new standard-of-care for relapsed Myeloma. We have subsequently commenced CARTITUDE5, a trial testing the activity of Ciltacaptagene up front in patients with Myeloma; the results are expected to be paradigm shifting. 

Another immunotherapy agent which is showing great promise is Cevostamab, a bi-specific T cell engaging antibody. We are commencing enrolment in an early-phase study to assess this agent currently, and it will offer another avenue for our patients to harness the potential of the immune system to control Myeloma.  

RPA Haematology maintained its position as the major NSW site for CAR-T cell clinical studies. We have now treated 43 lymphoma and 5 acute lymphoblastic leukaemia patients.

We have also been key participants in Phase I allogeneic CAR-T trials, being one of only 2 Australian sites in allogeneic CAR-T cells manufactured by CRISPR-Cas9 technology directed against CD19, BCMA and CD70, utilised in diffuse large B cell lymphoma, acute lymphoblastic leukemia, myeloma and T cell lymphoma respectively.  Several patients have been treated and the trials are continuing.

In addition, we have attracted a novel cell therapy trial (NKARTA) utilising allogeneic engineered CAR-bearing NK cells for patients with a wide range of B cell non-hodgkin lymphoma subtypes. Early results have been released and demonstrate high activity with minimal toxicity.

We continue to collaborate in the AGILE international multicentre phase III trial of Azacitidine ± Ivosidenib for patients diagnosed with Acute Myeloid Leukaemia (AML) with an IDH1 mutation. The significant benefit to patients treated with Azacitidine and Ivosidenib led to early closure of the trial and the results were published in the New England Journal of Medicine. We are also participating in two International phase III collaborative trials between the Australasian Leukaemia and Lymphoma Group (ALLG), German AML study group and Dutch HOVON group; the  AML-M23 and AML M-24 trials for the treatment of patients with newly diagnosed AML with an IDH or Flt3 mutation respectively, who are eligible for intensive chemotherapy and targeted therapy. Finally, we also participate in the ALL AML-M25 trials for elderly patients unfit for intensive chemotherapy but who may benefit from treatment with Venetoclax in combination with low dose cytarabine and pre-emptive Flt3 inhibition versus standard of care. There trials allow local patients to access new treatment options with the goal of improving survival.

The Institute of Haematology has been active in clinical and laboratory research in acute promyelocytic leukaemia (APL) for over 20 years. That program, led by Professor Harry Iland, culminated in major publications of the ALLG APML3 and practice-changing ALLG APML4 trials. Professor Harry Iland is the principal Investigator for this investigator-initiated phase I pharmacokinetic study of a novel oral formulation of arsenic trioxide (ATO) for use in patients with acute promyelocytic leukaemia (APL). National accrual was completed during 2020, and the last patient completed ATO and ATRA consolidation in January 2021. Results of part 1 of the study were presented at EHA in 2019, and the part 2 data which conformed bioequivalence with the intravenous formulation were presented at EHA in 2021. Statistical analysis is ongoing prior to manuscript submission in 2022. It is anticipated that the availability of an oral formulation of ATO for routine clinical use will significantly reduce utilisation of hospital resources and improve the overall treatment experience of patients with APL. Prof Iland is internationally recognised for his contributions to APL, and is a member of the European LeukemiaNet panel of experts that published updated diagnostic and treatment guidelines for APL in 2019. He has also collaborated with international APL experts on a retrospective analysis of the impact of cytogenetic abnormalities in APL patients treated with ATO-based regimens (accepted for publication in Blood Advances). Together with colleagues from the UK, North America and Australia, he is continuing a retrospective review of APL patients who present with extreme levels of white blood cell elevation, and a further study of the role of obesity in the frequency and severity of ATO-associated peripheral neuropathy during APL therapy. 

Our bone marrow transplant group is led by Associate Professor Stephen Larsen. Our unit is a major contributor to both national and international registries. In addition to ongoing accreditation by the Australian Blood and Marrow Donor Registry (ABMDR) and the Centre for International Blood and Marrow research (CIBMTR), our transplant service is the only NSW service accredited by the Therapeutic Good Administration (TGA). We have contributed to studies looking at the outcomes of patients receiving allogeneic bone marrow transplants in NSW, as well as the impact that COVID-19 has on transport of blood and bone marrow allografts into Australia. Our contribution has also included our experience with novel anti-fungal formations to prevent opportunistic infections in patients undergoing allogeneic bone marrow transplantation.

RPA is one of the leading centres for the treatment of Thalassemia and Sickle Cell Disease.

In thalassemia, RPA Haematology was the leader in Australian recruitment in the BELIEVE study of luspatercept, the beta-activin receptor which has been shown to increase erythropoiesis and haemoglobin levels in transfusion-dependent thalassemia. We are now conducting a trial in TMPRSS6 mRNA in thalassemia intermedia, investigating a novel mechanism to modulate erythropoiesis and iron metabolism. Prof Ho is chair of the Steering committee of the National haemoglobinopathies registry.

The Thrombosis Service of Haematology RPA entered its 7th year of operation in 2024.The Thrombosis team RPA provided extensive consultation on the risk of thrombosis and thrombocytopenia related to COVID19 vaccines. Dr Passam was a member of the THANZ Committee for VITT which developed national guidelines for the diagnosis and management of VITT. The Thrombosis team developed one of the 3 functional assays performed on a national scale for the diagnosis of VITT (Multiplate) and was one of the 2 centres in NSW to perform the immunological assay for the diagnosis of VITT. 

The Haemophilia unit, under the leadership of Drs Scott Dunkley, Freda Passam and Liane Khoo care for over 500 patients with haemophilia and other rare inherited bleeding disorders as part of the Comprehensive Haemophilia Treatment Centre.  The Haemophilia centre has participated in clinical trials for new therapies for haemophilia, including gene therapy, non-factor replacement (siRNA and antibody) and ultra-long acting FVIII, bringing cutting edge therapies to local patients. 

In collaboration with Professor Vivien Chen at Concord Hospital, senior scientist in-charge of coagulation, Mr Geoffrey Kershaw and Haematology Fellow, Dr Caroline Dix lead an Australia wide study on setting up a coagulation assay of Emicizumab, a new monoclonal antibody treatment that had revolutionised the treatment of Haemophilia A.

Our unit also undertakes supportive care research in haematology nursing. Tracy King myeloma CNC was recently awarded her PhD, exploring the symptoms and experiences of patients with myeloma taking corticosteroids as part of their treatment. Phase IV of Tracy's research is ongoing and was awarded a recent Cancer Services Research Grant by SLHD. 

Tracy King holds an affiliate position as Clinical Research Fellow with the Cancer Nursing Research Unit Sydney Nursing School where she collaborates with Prof Kate White and team on a range of other supportive care research projects. A summary of ongoing studies includes:

• Measurement properties of the Steroid Symptom Questionnaire Multiple Myeloma (SSQ-MM) in a multi-centre study with concurrent health related quality of life (HRQoL) measurement. Phase IV of a study, lead investigator Tracy King, to develop and evaluate a new Patient-Reported Outcome Measure to test the measure the impact of steroids associated with therapy for Myeloma. Recruiting at 4 NSW sites. 
• More efficient delivery of high-cost standard-of-care therapies in relapsed multiple myeloma using real-time feedback of patient-reported outcome measures: the MY-PROMPT-2 trial. Tracy King and Professor Joy Ho hold CI positions on this grant and are currently progressing the project for a large national multi-centre study. This study was awarded a $1,678,493 MRFF Rare Diseases Unmet Need grant and builds on previous work undertaken by this group in past year. 
• 'Implementation of routine enhanced clinical screening for chemotherapy-induced peripheral neurotoxicity: a feasibility study. CIPN-Screen'. Study lead investigator A/Prof Susanna Park of Brain and Mind Centre Sydney University, Tracy King is an associate investigator on this study.  
• Lenalidomide/bortezomib/dexamethasone therapy: Evaluation of a NSW Harmonised Approach and Review of Toxicity and Outcomes. Study leads Dr Georgia McCaughan and Dr Adam Bryant. Tracy King, Joy Ho, Christian Bryant and Kristina Whelan are investigators on this study which aims to audit outcomes across sites in NSW. 
• Lead investigator Tracy King has commissioned a Nursing White Paper: Optimising Multiple Myeloma Services in NSW through the contribution of Myeloma Advanced Practice Nurses. Prof Kate White and the CNRU team have been engaged to undertake this work. The White Paper is undertaken on behalf of the NSW Myeloma Working Group with associate investigators Prof C Ward, E/Prof D Joshua, J Jagger (NP), J Sipavicius (NP). 
• Myeloma Treatment Scheduler: Development of an online tool to create individual myeloma treatment schedules to be printed and provided to patients to aid understanding, improve adherence and enhance myeloma patient care. Myeloma Specialist Practice Network Haematology Society of Australia and New Zealand (HSANZ). T King, J Hempton, J Jagger, A Snowden, J Sipavicius, C Woodrow, S Haines.  

Under Prof Ho's direction our Myeloma Research laboratory has continued to develop its capacity for basic science and translation/diagnostic work. We have focused on molecular diagnostics, sensitive assessments of residual disease, and the greater understanding of the immune microenrviroment. 

We have also established a novel next-generation sequencing platform to define mutational load in malignant cells from Myeloma patients at diagnosis and with relapsed disease. This is currently undergoing validation and will provide the most refined prognostic tool currently available. 

We have set up a state-of-the-art platform (Euroflow) to monitor minimal residual disease (MRD) in Multiple Myeloma patients. This has established RPA as the only site in Australia on the Eastern seaboard with the capacity to assess Myeloma MRD with a validated assay. We have established a project to use this assay to assess level of Multiple Myeloma in peripheral blood samples collected early during the commencement of therapy. Initial data suggests that this will demonstrate which patients are destined to respond poorly early, so that changes to therapy can be made to improve outcomes. This is being performed as a collaborative project across 4 hospitals in NSW. 

We have also studied the immune system of Myeloma patients using Single Cell Next-Generation Sequencing, revealing the T cell compartment in the bone marrow in greater detail than seen before (manuscript in preparation). This will help us to understand how Myeloma evades immune control. 

The Institute of Haematology at RPA also has a number of laboratory studies into benign haematology. These include the novel characterisation of myeloid cells in patients with thalassaemia, defining the platelet proteome in type 2 diabetes mellitus and the evaluation of thrombophilia studies in patients with ischaemic strokes.

The ALLG is currently preparing to open an AML platform trial which will examine the role of novel combinations of targeted therapy guided by a comprehensive measurable residual disease (MRD) monitoring program. Prof Harry Iland is the chair of the MRD reference committee for the study which has the potential to dramatically change the way in which patients with AML are managed during remission.

The advent of next generation sequencing (massively parallel sequencing) has changed the diagnostic paradigm for patients with haematological malignancies. The Molecular Haematology laboratory at RPAH has conducted an extensive validation program of a myeloid gene panel with the goal of achieving NATA accreditation, and those activities supported the unit's participation in a joint ALLG / RCPAQAP initiative assessing candidate gene panel testing for AML which was published in Pathology.