Clinical Research Directory

ENERGIA: Personalized Exercise Program for Fatigue in Patients With Myeloproliferative Neoplasms and Chronic Myeloid Leukemia

This study evaluates whether a personalized, supervised exercise program can improve fatigue and physical function in patients with myeloproliferative neoplasms (MPN) and chronic myeloid leukemia (CML). Although many patients achieve good disease control with modern therapies, they often experience persistent symptoms such as fatigue that significantly affect daily life. Participants will take part in a 12-week exercise program that includes aerobic and resistance training, tailored to their individual fitness level and clinical condition. The program consists of two supervised sessions per week, along with additional home-based aerobic activity. Before and after the program, participants will undergo comprehensive assessments, including cardiopulmonary exercise testing, physical function tests, questionnaires on fatigue and quality of life, and blood sample collection. The study aims to determine whether this type of exercise program is feasible and safe, and whether it can reduce fatigue and improve physical capacity, quality of life, and biological markers related to inflammation and metabolism. Participants will also be followed after the intervention to evaluate whether the benefits are maintained over time.

TCRαβ-depleted Progenitor Cell Graft With Additional Memory T-cell DLI, Plus Selected Use of Blinatumomab, in Naive T-cell Depleted Haploidentical Donor Hematopoietc Cell Transplantation for Hematologic Malignancies

Patients less than or equal to 21 years old with high-risk hematologic malignancies who would likely benefit from allogeneic hematopoietic cell transplantation (HCT). Patients with a suitable HLA matched sibling or unrelated donor identified will be eligible for participation ONLY if the donor is not available in the necessary time. The purpose of the study is to learn more about the effects (good and bad) of transplanting blood cells donated by a family member, and that have been modified in a laboratory to remove the type of T cells known to cause graft-vs.-host disease, to children and young adults with a high risk cancer that is in remission but is at high risk of relapse. This study will give donor cells that have been TCRαβ-depleted. The TCR (T-cell receptor) is a molecule that is found only on T cells. These T-cell receptors are made up of two proteins that are linked together. About 95% of all T-cells have a TCR that is composed of an alpha protein linked to a beta protein, and these will be removed. This leaves only the T cells that have a TCR made up of a gamma protein linked to a delta protein. This donor cell infusion will be followed by an additional infusion of donor memory cells (CD45RA-depleted) after donor cell engraftment. This study will be testing the safety and effects of the chemotherapy and the donor blood cell infusions on the transplant recipient's disease and overall survival.

A First-in-Human Study of HLA-Partially to Fully Matched Allogenic Cryopreserved Deceased Donor Bone Marrow Transplantation for Patients With Hematologic Malignancies

The goal of this clinical trial is to determine the safety and feasibility of allogeneic transplantation with bone marrow from a deceased donor in patients with acute and chronic leukemias, myelodysplastic syndrome, and certain lymphomas. Patients will either receive myeloablative conditioning or reduced intensity conditioning regimen prior to the transplant. Patients will be followed for 56 days for safety endpoints and remain in follow-up for one year.

TACrolimus Targeted Immunosuppression Cessation in ALlogeneic HCT

The purpose of this study is to test the feasibility and safety of early cessation of tacrolimus following allogeneic hematopoietic cell transplantation (HCT). Post-HCT tacrolimus is given to prevent graft-vs-host-disease (GVHD), but with the use of post-transplant cyclophosphamide (PTCy), the modern approach to GVHD prevention, GVHD rates have reduced markedly.

Open-label Study of Asciminib for CML-CP or CML-AP Patients With T315I Mutation Who Are Resistant, Intolerant or Ineligible to Ponatinib.

The objective of this Phase II study is to assess the potential of asciminib in managing CML-CP or CML-AP in patient carrying the T315I mutation. The presence of this mutation introduces treatment difficulties due to the limited available options. The study seeks to collect additional data on the effectiveness and safety of asciminib for these patients. By determining the drug's capacity to manage the disease and enhance patients outcomes, the study is designed to fill the unmet medical need and potentially offer a new therapeutic path for patients at a treatment deadlock.

Quality of Life and Care Organization of Patients With Chronic Myeloid Leukemia in the Lombardy Hematology Network

The primary objective of the study is to assess the impact of the organizational model of the hematology center on the quality of life of patients with CML estimated through standardized tools (EORTC QLQ-30, CML24) and through the patient's opinion regarding aspects of the quality of care.

Improving Treatment Outcomes in Chronic Myeloid Leukaemia Patients Using Imatinib and Artesunate Combination Therapy

Chronic myeloid leukaemia (CML) is a blood cancer with an annual worldwide incidence of 1/100,000 population. Imatinib is used for the treatment of CML and has significantly improved the management of the disease. However, the incidence of treatment failure due to imatinib resistance has become a considerable burden (Sherbenou et al., 2007). Artesunate, an antimalarial drug, is reported to have anti-neoplastic effect either singly or in synergy with already established anti-neoplastic agents (Krishna et al., 2015). The aim of the study is to evaluate the clinical effectiveness of an Imatinib-artesunate combination compared to imatinib alone and its possibility as an alternative option in the management of sub-optimal response in CML patients especially in low- and middle- income country like Nigeria where second line tyrosine kinase inhibitor may be out of reach. The specific objectives are to: 1. Assess the safety of artesunate use beyond its traditional antimalarial dosing period in CML patients. 2. Compare treatment outcomes between patients on imatinib alone and patients on imatinib plus artesunate at 3, 6 and 12-months of follow-up. 3. Determine the effect of imatinib and artesunate combination on the achievement of major molecular remission in CML patients with sub-optimal response to imatinib. 4. Determine the effect of artesunate on imatinib pharmacokinetics following co-administration of the two drugs. The main questions it aims to answer is: * Does the use of artesunate in combination with imatinib in newly diagnosed CML patient give a better therapeutic outcome than using imatinib alone? * Does combining artesunate with imatinib in CML patients with sub-optimal response to imatinib improve patients' response to imatinib? * Does combining artesunate with imatinib in CML patients affect the pharmacokinetic parameter of imatinib? * Is it safe to take artesunate at 4mg/day (not exceeding 200mg/day) for a 14day cycle in CML patients as demonstrated in other forms of cancer? Participants will be assigned to one of the groups of the study and continue imatinib medication irrespective of the group assigned and come to clinic once a month for follow-up. Clinic visits will be immediately after a cycle of artesunate for groups B and C.

Identification of BCR::ABL1 Mutations by Digital PCR in CML

The goal of this study is to asses the ability of digital PCR (ddPCR) to detect actionable mutations in adult CML patients with failure of TKI therapy. The main objective of the study is it aims to answer is to assess whether ddPCR is at least as effective as NGS in detecting actionable (2GTKI-resistant) mutations. To accomplish this aim, samples of participants treated according to clinical practice, will be taken and analyzed for the presence of BCR::ABL1 KD mutations by ddPCR.

Provision of TCRγδ T Cells and Memory T Cells Plus Selected Use of Blinatumomab in Naïve T-cell Depleted Haploidentical Donor Hematopoietic Cell Transplantation for Hematologic Malignancies Relapsed or Refractory Despite Prior Transplantation

This study seeks to examine treatment therapy that will reduced regimen-related toxicity and relapse while promoting rapid immune reconstitution with limited serious graft-versus-host-disease (GVHD) and also improve disease-free survival and quality of life. The investigators propose to evaluate the safety and efficacy of selective naive T-cell depleted (by TCRɑβ and CD45RA depletion, respectively) haploidentical hematopoietic cell transplant (HCT) following reduced intensity conditioning regimen that avoids radiation in patients with hematologic malignancies that have relapsed or are refractory following prior allogeneic transplantation. PRIMARY OBJECTIVE: * To estimate engraftment by day +30 post-transplant in patients who receive TCRɑβ-depleted and CD45RA-depleted haploidentical donor progenitor cell transplantation following reduced intensity conditioning regimen without radiation. SECONDARY OBJECTIVES: * Assess the safety and feasibility of the addition of Blinatumomab in the early post-engraftment period in patients with CD19+ malignancy. * Estimate the incidence of malignant relapse, event-free survival, and overall survival at one-year post-transplantation. * Estimate incidence and severity of acute and chronic (GVHD). * Estimate the rate of transplant related mortality (TRM) in the first 100 days after transplantation.

Evaluation of CD47, "Do Not Eat Me" Signal Expression in Chronic Myeloid Leukemia

Chronic myeloid leukemia is a myeloid neoplasm characterized by the overproduction of mature granulocytes . Cluster of differentiation 47 (CD47) is a membrane protein, which is over-expressed by virtually all cancers and regulates many signaling systems associated with tumor growth and invasion. Following CD47 binding to the inhibitory receptor (signal regulatory protein, SIRPα) on macrophages, the CD47-receptor complex sends a "do not eat me" anti-phagocytic signal to prevent phagocytosis . This balance is tipped by cancer cells, which adopt the "self" signal and upregulate CD47 expression to evade immune surveillance and subsequent destruction. Elevated expression of CD47 has been observed in ovarian carcinoma cell lines , murine myeloid leukemias , leukemic stem cells and several solid tumors . Flow cytometry revealed high surface expression of CD47 on 73% of samples collected from the bone marrow of multiple myeloma (MM) patients . High CD47 expression on six different primary effusion lymphoma (PEL) cell lines compared to peripheral blood mononuclear cells (PBMC) was found . Additionally, in acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), and several non-Hodgkin's lymphoma (NHL) subtypes, increased CD47 expression is correlated with adverse clinical outcomes . Hematological malignancies, even at onset, present with widespread bone marrow and peripheral blood involvement and many are still without effective systemic curative therapies . Most CML patients have deep and durable responses when treated with BCR::ABL1 tyrosine kinase inhibitors, which might be influenced by long-term toxicities during the treatment . CD47 "don't eat me signal" expression not evaluated in CML. the aim of the study To detect CD47 expression by flow cytometry in CML patients. To study the correlation between BCR::ABL1 gene and CD47 expression in CML patients . Evaluation of the role CD47 as predictor of CML patient outcome

Long-term Risk of Second Primary Malignancies for Chronic Myeloid Leukaemia in the French Imatinib-based SPIRIT Trial

Imatinib is a tyrosine kinase inhibitor that has improved the prognosis of patients with chronic myeloid leukemia (CML). CML has become a chronic disease requiring long-term administration of imatinib. Late adverse effects were initially unknown. Since 2005, imatinib has been suspected to increase the risk of second primary malignancies (SPM). Through the French "STI571 Prospective Randomized Trial" (SPIRIT), we studied the incidence of SPM after more than 20 years of exposure, and treatment strategies for CML and SPM at their occurrence.

CD34+ (Malignant) Stem Cell Selection for Patients Receiving Allogenic Stem Cell Transplant

The purpose of this study is to learn more about the effects of (classification determinant) CD34+ stem cell selection on graft versus host disease (GVHD) in children, adolescents, and young adults. CD34+ stem cells are the cells that make all the types of blood cells in the body. GVHD is a condition that results from a reaction of transplanted donor T-lymphocytes (a kind of white blood cell) against the recipient's body and organs. Study subjects will be offered treatment involving the use of the CliniMACS® Reagent System (Miltenyi Biotec), a CD34+ selection device to remove T-cells from a peripheral blood stem cell transplant in order to decrease the risk of acute and chronic GVHD. This study involves subjects who are diagnosed with a malignant disease, that has either failed standard therapy or is unlikely to be cured with standard non-transplant therapy, who will receive a peripheral blood stem cell transplant. A malignant disease includes the following: Chronic Myeloid Leukemia (CML) in chronic phase, accelerated phase or blast crisis; Acute Myelogenous Leukemia (AML); Myelodysplastic Syndrome (MDS); Juvenile Myelomonocytic Leukemia (JMML); Acute Lymphoblastic Leukemia (ALL); or Lymphoma (Hodgkin's and Non-Hodgkin's).

EPIgenetics and in Vivo Resistance of Chronic Myeloid Leukemia Stem Cells to Tyrosine Kinase Inhibitors

Primary objective : To identify epigenetic dysregulations of in vivo TKI-resisting CML cells Hypothesis : An epigenetic dysregulation is involved in the in vivo survival of a CML cell subclone despite the use of TKIs

Chronic Myeloid Leukemia (CML) Real-Life Database

Establish the largest possible real-life cohort collecting long-term follow-up of a maximum number of CML patients in order to carry out observational studies: epidemiological, identification of subgroups according to their response to treatment, evaluation of new molecules in real life, therapeutic discontinuations, impact of the evolution of recommendations, etc.