Trials
Although therapies are successful in curing or prolonging the lives of many patients, they can cause considerable suffering (symptoms and side effects), health-related alterations in QoL (Quality of Life) and disturbances in psychosocial functioning.
Preserving and maintaining the patient’s well-being is the main goal of medical practice, and is crucial in the treatment of hematological patients.
Another important aspect to be considered in the treatment of hematological diseases is the issue of side effects that may result from therapy and that are often underestimated in routine hematological research and practice.
Ongoing trials
“Efficacy and safety of Luspatercept for the treatment of anemia due to myelodysplastic syndromes with del5q refractory/resistant/intolerant to previous treatments and requiring red blood cell transfusions.”
Eudract number 2021-001538-20
Phase II, multicenter, national, prospective, single-arm study.
Myelodysplastic syndromes, primarily affecting older adults, are a heterogeneous group of clonal disorders of hematopoietic stem cells characterized by ineffective hematopoiesis that manifest clinically as anemia, neutropenia, and/or thrombocytopenia of variable severity; these often result in RBC- transfusion dependent (TD) anemia, increased risk of infection, and/or hemorrhage, as well as a potential to progress to acute myeloid leukemia (AML).
Treatment goals for patients with lower-risk myelodysplastic syndromes (MDS) include transfusion independence (TI), improvement in hemoglobin (Hb) levels, and maintenance of or improvement in quality of life (QoL).
Therapy with Lenalidomide has been approved for MDS patients with del5q and RBC-TD. However, approximately one third of patients are refractory/resistant/intolerant to treatment and will require additional treatment options.
Unfortunately, patients with MDS with
del5q refractory/resistant/intolerant to lenalidomide are excluded from clinical trials that evaluate novel treatments for the anemia of RBC TD lower risk MDS. Therefore, treatment of anemia in such patients is an unmet need.
Luspatercept is indicated for the treatment of adult patients with transfusion-dependent anaemia associated with beta-thalassaemia and due to very low, low and intermediate-risk MDS with ring sideroblasts, who had an unsatisfactory response to or are ineligible for erythropoietin-based therapy. It is not indicated for other MDS subtypes.
The objective of the study is to evaluate the effect of Luspatercept on RBC TI (lack of transfusions for 8 consecutive weeks within the first 24 weeks) in subjects with MDS with del5q with IPSS-R very low,
low, or intermediate risk and < 5% bone marrow blasts, resistant/refractory/intolerant to
lenalidomide and RBC TD.
Observational study to evaluate patient-reported outcomes in Paroxysmal Nocturnal Hemoglobinuria”.
Observational non-interventional prospective multicenter international study.
Acquired aplastic anemia (AAA) and paroxysmal nocturnal hemoglobinuria (PNH) are interrelated rare diseases belonging to the group of bone marrow failure syndromes.
Given the complexity of PNH and the fact that PNH is not a malignant disease, the cancer-specific tools used so far have proved inappropriate to adequately assess PROs in this patient group.
The approval of new treatments for AAA / PNH require PRO for clinically meaningful results. The evaluation of the new tool can provide new information on clinically significant changes and unmet needs in PNH patients.
Recently, a new tool PRO specific for AAA / PNH (EORTC QLQ-AA / PNH) was created according to the EORTC guidelines and underwent an initial Phase 2 and 3 evaluation. This tool consists of 54 elements, translated into Italian and will be used to identify patients’ complaints. The tool can identify differences in QoL based on hemolysis and treatment response that can lead to the treatment choice and effectiveness.
“Eltrombopag for the treatment of thrombocytopenia due to low- and intermediate risk myelodysplastic syndromes”.
EUdraCT number: 2010-022890-33
https://www.clinicaltrialsregister.eu/ctr-search/search?query=EQOL-MDS
International multicenter, single-blind, randomized, placebo-controlled, study.
The aims of the study are to evaluate the efficacy and safety of Eltrombopag, a platelet-poietic factor, on the treatment of thrombocytopenia in patients with low and intermediate-1 risk MDS.
Specifically, it will be evaluated the proportion of patients achieving a complete response (CR) or
response (R) during the treatment period compared to the proportion of patients in the placebo group. Furthermore,
safety and tolerability in terms of frequency of adverse events (AE), over and serious
adverse events (SAE).
The patient enrollment phase was completed on 31 October 2021.
To see the preliminary result of the study, please see the following article:
Eltrombopag versus placebo for low-risk myelodysplastic syndromes with thrombocytopenia (EQoL-MDS): phase 1 results of a single-blind, randomized, controlled, phase 2 superiority trial. Lancet Haematol. 2017 Mar;4(3):e127-e136. doi: 10.1016/S2352-3026(17)30012-1. Epub 2017 Feb 3.
https://www.ncbi.nlm.nih.gov/pubmed/28162984,
Completed trials
“Observational study to evaluate patient-reported outcomes in Gaucher disease.”
Observational, national, multicenter, prospective study.
Gaucher Disease (GD) is an autosomal recessive disease caused by the deficiency of lysosomal β-glucocerebrosidase enzyme, which leads to storage of non-degraded substrate glucocerebroside and other glycolipids, thus causing damage in different organs.
Three major clinical types are identified:
type 1 – Non-neuronopathic Gaucher disease, type 2 – Acute neuronopathic Gaucher disease, type 3 – Chronic neuronopathic Gaucher disease.
Type 1 is the most common form.
Treatment consists of enzyme replacement therapy (ERT), indicated for patients with type 1 GD who exhibit clinical signs and symptoms of the disease.
Patient-reported outcomes – PROs (patient-reported outcomes) include all aspects of quality of life (QoL) and symptoms related to the disease and treatment.
The implementation of PROs in patients with GD is indispensable in the clinical context. There are many generic tools available to measure the impact of disease on patient QoL. However, there is no PROs measurement tool that has been developed specifically for GD patients. The development of such a tool is useful for physicians and paramedics to have a deeper understanding of the impact of the patient’s disease.
The original GD PRO questionnaire was translated into Italian according to ISPOR and FDA guidelines and has been validated during the study, in patients with symptomatic GD, naïve to treatment and started on the prescribed treatment.
A randomized study to evaluate the efficacy of 5-Aza for post-remission therapy of acute myeloid leukemia in elderly patients.
EUdraCT number: 2010-019710-24
https://www.clinicaltrialsregister.eu/ctr-search/trial/2010-019710-24/IT
Italian, randomized, prospective, open-label, multicenter, phase III study.
The object of the study was the evaluation of the effects of maintenance therapy with injectable Azacitidine for the complete remission in elderly patients suffering from acute myeloid leukemia.
This pathology is characterized by a poor response to treatments and by early relapses in patients which achieve remission.
This results in short survival. The patients enrolled, in complete remission after conventional induction and consolidation chemotherapy treatment, were randomized into two groups: one (experimental arm) which was treated with Azacitidine via s.c. or i.v. and with the best supportive therapy and the other who received only the best supportive therapy (control arm).
This trial aimed to evaluate the differences in disease-free survival overall survival, adverse events and quality of life between the two groups.
The final study results were presented during the European Hematological Congress EHA 2022.
Accuracy of alternative TP53 somatic mutational
and expression analyses for the prognostication
of myelodysplastic syndrome
National, multicenter, non-interventional, prospective, observational study.
In patients with MDS with del5q the prognosis of is variable and dependent on several
factors, such as blast count, transfusion dependence, thrombocytopenia, more than one
additional cytogenetic abnormalities, age and other biological variables. The dissemination of an accurate laboratory method for determining the prognosis of these patients is useful for the therapeutic choice, especially in patients affected by MDS with del5q with a severe prognosis.
The study aimed to evaluate the concordance between TP53 expression in IHC and in qPCR realtime method on BM blood sample, in terms of proportion of patients with concordance.
Were also evaluated the frequency of TP53 somatic mutations in the MDS sample by SNP single assay and the prognostic value on disease progression of the mutational status on BM blood
sample compared to the expression in IHC and in qPCR realtime relative method
on BM blood sample
The study has been formally closed on October 2019, due to futility.
Efficacy of eltrombopag plus lenalidomide combination therapy in patients with IPSS low and intermediate-risk myelodysplastic syndrome with isolated del5q:
a multicenter, randomized, double-blind, placebo-controlled study
EUdraCT number: 2015-000362-53
The present multicenter, international (Italy, France, Greece) randomized, double-blind, placebo controlled,
prospective, phase II study
Standard care is represented by Lenalidomide. Patients with this disease may develop at the onset thrombocytopenia or develop it during treatment with Lenalidomide. The use of the experimental drug Eltrombopag could prevent platelet count decrease.
The aim of the clinical trial was to evaluate the efficacy and safety of Eltrombopag for the treatment of thrombocytopenia in the patients taking lenalidomide for MDS treatment with isolated del5q. The primary objective is toassess the results of the Eltrombpag treatment for thrombocytopenia and hemorrhagic events in the experimental arm versus the placebo-controlled arm.
Furthermore, adverse events, cytogenetic responses and their duration, changes in hemoglobin levels and transfusion independence, survival and quality of life of the two groups were compared.
The study has been formally closed on Sept 2018, due to futility.
Lenalidomide for Myelodysplastic Syndromes: Efficacy, Safety, Cardiac Changes, and Quality of Life
EUdraCT number: 2008-000547-34
https://www.clinicaltrialsregister.eu/ctr-search/search?query=Quality+of+Life+(QOL)
The study aimed to evaluate the effect of lenalidomide on cardiac remodelling and its correlation with erythroid response in anemic patients with 5q-, low or intermediate-1 risk MDS, the safety and efficacy of Lenalidomide in terms of response (response / no response) for the treatment of anemia in patients with MDS, the changes in QoL in patients undergoing treatment.
Study results:
Oliva EN, Cuzzola M., Nobile F., et al. Changes in RPS14 expression levels during lenalidomide treatment in Low-and Intermediate-1-risk Myelodysplastic. European Journal of Haematology 85(3):231-5. 2010 September https://www.ncbi.nlm.nih.gov/pubmed/20491881
Oliva EN., Cuzzola M., Aloe Spiriti MA, et al., Biological Activity of lenalidomide in myelodysplastic sindromes with del5q: results of gene expression profiling from a multicenter phase II study. Ann Hematol. 2012 Sep 16. https://link.springer.com/article/10.1007/s00277-012-1569-0
Oliva EN., Latagliata R., Laganà C., et al. Lenalidomide in Low-and Intermediate-1 IPSS risk myelodysplastic syndromes with del(5q): an Italian phase II trial of health-related quality of life, safety, and afficacy. Leuk Lymphoma. 2013 Feb 25. https://www.ncbi.nlm.nih.gov/pubmed/23432724
“Lenalidomide for Myelodysplastic Syndromes: Efficacy, Safety, Cardiac Changes, and Quality of Life”
Numero Eudract 2008-000547-34
https://www.clinicaltrialsregister.eu/ctr-search/search?query=Quality+of+Life+(QOL)
Obbiettivo della sperimentazione è stato quello di valutare l’efficacia del trattamento con Lenalidomide in pazienti adulti con anemia dovuta a sindrome mielodisplastica a rischio basso o intermedio con anomalia citogenetica delezione del braccio corto del cromosoma 5. Oltre alla valutazione della risposta ematologica, citogenetica e molecolare e della tossicità, è stata valutata la risposta sulla qualità della vita.
La ricerca ha prodotto le seguenti pubblicazioni:
Oliva EN, Cuzzola M., Nobile F., et al. Changes in RPS14 expression levels during lenalidomide treatment in Low-and Intermediate-1-risk Myelodysplastic. European Journal Of Haematology 85(3):231-5. 2010 September https://www.ncbi.nlm.nih.gov/pubmed/20491881
Oliva EN., Cuzzola M., Aloe Spiriti MA, et al., Biological Activity of lenalidomide in myelodysplastic sindromes with del5q: results of gene expression profiling from a multicenter phase II study. Ann Hematol. 2012 Sep 16. https://link.springer.com/article/10.1007/s00277-012-1569-0
Oliva EN., Latagliata R., Laganà C., et al. Lenalidomide in Low-and Intermediate-1 IPSS risk myelodysplastic syndromes with del(5q): an Italian phase II trial of health-related quality of life, safety, and afficacy. Leuk Lymphoma. 2013 Feb 25. https://www.ncbi.nlm.nih.gov/pubmed/23432724
Evaluation of the quality of life in elderly patients with acute myeloblastic leukemia undergoing treatment.
Observational study supported by AIL (Italian Association for Acute Leukaemia)
In this study, elderly patients with acute myeloid leukemia since diagnosis were observed, with the aim of evaluating changes in the quality of life related to the disease and its treatments.
Study results:
Oliva EN, Nobile F., Alimena G., et al. (2011) Quality of life in elderly patients with acute myeloid leukemia: patients may be more accurate than physicians. Haematologica 2011) https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3084916
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