Posted 2 years ago by Wales Gene Park
The current national acute lymphoblastic leukaemia (ALL) trial in adults investigated whether a low (reduced) intensity chemotherapy regimen prior to transplant could improve the outcome of patients with ALL who are over 40 years of age. The results (60% 2 year survival) are very encouraging but patients who come to transplant with small amounts of 'residual' disease had less good outcomes. The goal of this trial is to see if a slightly stronger chemotherapy regimen (involving total body irradiation, (TBI)) can improve results by reducing the chance of the disease coming back (relapsing) without increasing the chance of not surviving the transplant. Up to 242 patients will be 'randomised' to the trial to receive either the established chemotherapy of fludarabine and melphalan or cyclophosphamide and TBI to compare the outcomes between the two treatment regimens. Other measures to reduce relapse will be the earlier use of donor white cell infusions...
Posted 10 months ago by Wales Gene Park
Summary: Myelofibrosis (MF) is a cancer of the bone marrow that disrupts the production of blood cells. Symptoms of MF include anaemia (low red cell levels), weakness, tiredness and often an enlarged spleen. Standard treatment can involve chemotherapy, radiotherapy, a stem cell transplant or treatment with a drug called ruxolitinib. Ruxolitinib targets the specific cells that play a part in the development of MF, and is the only drug licenced to treat MF. Previous research has shown that ruxolitinib is good at reducing symptoms of MF and decreasing the size of the spleen. However, the majority of patients do not show a complete response to ruxolitinib, meaning that another treatment needs to be added to ruxolitinib to improve the outcome for patients. This study will test whether combining ruxolitinib with another drug called a bromodomain and extra terminal inhibitor (BETi) is safe for MF. Research has suggested that combining these...
Posted 1 year ago by Wales Gene Park
Brief Summary To collect and describe demographics, disease-management, and treatment outcomes of Myelodysplastic Syndromes (MDS) patients who are newly diagnosed and classified according to the World Health Organization (WHO) criteria. To perform observational studies concerning relevant scientific research questions in MDS using clinical data and biological samples, and to present relevant research outcomes in the fields of diagnosis and prognostication, health related quality of life issues, health economics, and risk stratification for newly developed classes of drugs. To disseminate results of the studies to all stakeholders involved. Methodology Data on patients with MDS will be collected prospectively at diagnosis and at 6-months intervals after diagnosis. The data will be gathered by seventeen (or more) countries that are represented within the LeukemiaNet MDS Working Party and will be combined in one central European Database. Data analyses will be conducted by the Data Management Centre at the University of York in various...
Posted 10 months ago by Wales Gene Park
Brief Summary The purpose of the phase 1 portion (dose escalation) of the study will be to establish an optimally safe and biologically active recommended phase 2 dose (RP2D) and/or to determine maximum tolerated dose (MTD) for gilteritinib in sequential combination with fludarabine, cytarabine and granulocyte colony-stimulating factor (FLAG). The purpose of the phase 2 portion (dose expansion) is to determine complete remission (CR) rates and composite complete remission (CRc) rates after two cycles of therapy. The study will also assess safety, tolerability and toxicities of gilteritinib in combination with FLAG, evaluate FLT3 inhibition, assess pharmacokinetics (PK), perform serial measurements of minimal residual disease, obtain preliminary estimates of 1-year event free survival (EFS) and overall survival (OS) rate and assess the acceptability as well as palatability of the formulation. One cycle is defined as 28 days of treatment. A participant completing 2 cycles in phase 1 or 2 will have...
Posted 1 year ago by Wales Gene Park
Brief Summary This is a phase 1B, multi-center, dose-finding study of glofitamab administered in combination with obinutuzumab (Gazyva; [G]), rituximab (R) and standard doses of CHOP (G/R-CHOP or R-CHOP) in participants with r/r NHL and G/R CHOP or Pola-R-CHP in participants with untreated diffuse large B-cell lymphoma (DLBCL). Evaluating the safety, preliminary activity, pharmacokinetic (PK), and pharmacodynamic effects of this combination will be the main objectives of this study. The study is divided in two parts: Part I: Dose finding in participants with r/r NHL; test use of G vs R in Cycle 1 Part II: Dose Expansion. The maximum tolerated dose or optimal biological dose (MTD or OBD) will be further assessed in participants with untreated DLBCL (>18 years of age with an age-adjusted International Prognostic Index (IPI) of 2-5). Glofitamab will be studied in combination with R-CHOP and Pola-R-CHP.
Posted 1 year ago by Wales Gene Park
Brief Summary A Phase 3b, open-label, single-arm, rollover study to evaluate the long-term safety of luspatercept, to the following subjects: Subjects receiving luspatercept on a parent protocol at the time of their transition to the rollover study, who tolerate the protocol-prescribed regimen in the parent trial and, in the opinion of the investigator, may derive clinical benefit in the opinion of the investigator from continuing treatment with luspatercept. Placebo arm subjects from parent protocol (at the time of unblinding or in follow-up) crossing over to luspatercept treatment (provided subjects have met all requirements for entering the rollover study as per the parent protocol). Subjects in the follow-up phase previously treated with luspatercept or placebo in the parent protocol will continue into long-term post-treatment follow-up in the rollover study until the follow-up commitments are met (unless they meet requirements as per parent protocol to cross-over to luspatercept treatment). The study design...
Posted 1 year ago by Wales Gene Park
Brief Summary This study is a multicenter, open-label study of polatuzumab vedotin administered by intravenous (IV) infusion in combination with rituximab, gemcitabine and oxaliplatin (R-GemOx) in participants with relapsed or refractory diffuse large B-cell lymphoma (DLBCL). The study comprises of two stages: a safety run-in stage and a randomized controlled trial.
Posted 4 years ago by Wales Gene Park
Conditions where lymphocytes have become cancerous are called lymphoproliferative disorders and include Chronic lymphocytic leukaemia (CLL) Mantle cell lymphoma Follicular lymphoma Hairy cell leukaemia Splenic lymphoma with villous lymphocytes Doctors want to find out more about these cancerous cells. In this study you will give samples of blood and any extra bone marrow or tissue you may have removed during routine procedures. You will also give a sample of spit (saliva). Researchers will look at both abnormal and normal cells in these samples. They will look for genes, including a particular gene called the ‘immunoglobulin gene’ that help the cancer cell to survive. And, for other gene and chromosome changes that may in future help them predict the outcome of these diseases. The aim of this study is to understand more about how changes to certain genes, proteins and sugars could affect how these diseases develop. This may help develop...
Posted 1 year ago by Wales Gene Park
Brief Summary Trial Subjects (patients), will receive single infusions of pembrolizumab every 3 weeks until disease progression or unacceptable toxicity develops. They will receive radiotherapy at week 12. Detailed Description Trial Subjects (patients) who are deemed eligible for the trial will be administered a single infusion of pembrolizumab (200mg) every 3 weeks. At week 12, patients will be planned to start radiotherapy at a dose of 12 Gray (Gy) in 3 fractions which will be given concomitantly with pembrolizumab. Patients who progress on pembrolizumab before week 12 will start radiotherapy as soon as possible after progression. Following completion of radiotherapy, patients will continue receiving pembrolizumab at 3 weekly intervals for a maximum of 2 years until disease progression or unacceptable toxicity develops. Patients on pembrolizumab will be seen every 3 weeks until 2 years after study entry, while Patients who progressed/ stopped pembrolizumab will be seen annually for survival/disease status...
Posted 1 year ago by Wales Gene Park
Brief Summary A Phase 3, multicenter, open-label, randomized study to evaluate the efficacy and safety of fedratinib compared to best available therapy (BAT) in subjects with DIPSS (Dynamic International Prognostic Scoring System)-intermediate or high-risk primary myelofibrosis (PMF), post-polycythemia vera myelofibrosis (post-PV MF), or post-essential thrombocythemia myelofibrosis (post-ET MF) and previously treated with ruxolitinib. The primary objective of the study is to evaluate the percentage of subjects with at least 35% spleen volume reduction in the fedratinib and the BAT arms. Detailed Description This Phase 3, multicenter, randomized, two-arm, open-label study will include subjects with intermediate or high-risk (as per the DIPSS score) primary myelofibrosis (PMF), postpolycythemia vera myelofibrosis (post-PV MF), or post-essential thrombocythemia myelofibrosis (post-ET MF). This study will be conducted in compliance with International Council for Harmonisation (ICH) Good Clinical Practices (GCPs). Study design includes: A 28-day Screening Period 2:1 Randomization to fedratinib or best available therapy (BAT) Stratification...
Posted 2 years ago by Wales Gene Park
The main purpose of this study is : To establish which number of doses of gemtuzumab ozogamicin (up to a maximum of 3 doses) is tolerated and can be safety delivered in combination with cytarabine plus mitoxantrone or liposomal daunorubicin in induction To compare mitoxantrone (anthracenedione) & cytarabine with liposomal daunorubicin (anthracycline) & cytarabine as induction therapy. (Randomisation 1 (R1) closed early to recruitment on 8th September 2017, due to liposomal daunorubicin manufacturing issues resulting in unavailability of the drug.) To compare a single dose of gemtuzumab ozogamicin with the optimum tolerated number of doses of gemtuzumab ozogamicin (identified by the dose-finding study) when combined with induction chemotherapy. To compare two consolidation regimens: high dose cytarabine (HD Ara-C) and fludarabine & cytarabine (FLA) in standard risk patients. To compare the toxicity and effectiveness of two haemopoietic stem cell transplant (HSCT) conditioning regimens of different intensity: conventional myeloablative conditioning (MAC) with...
Acute Myeloid Leukaemia (AML) / Noah's Ark Children's Hospital for Wales
Posted 1 year ago by Wales Gene Park
Brief Summary This trial is to investigate the combination of selumetinib and dexamethasone in the treatment of acute lymphoblastic leukaemia (ALL) in both adults and children. Phase I is to find the most suitable dose of selumetinib to safely give with dexamethasone. Phase II will use this dose to find out how well the combination works. Detailed Summary Acute lymphoblastic leukaemia (ALL) is the most common childhood cancer worldwide. The overall newly diagnosed ALL cure rate is approaching 90% however children with relapsed ALL often do not survive. The frequency of ALL in adults is significantly lower however more challenging to treat compared to childhood ALL. Adult ALL is more resistant to chemotherapy and patient have reduced treatment tolerance (particularly the elderly population) therefore overall survival rates are low. Therefore there is a need to develop more effective treatment which improves survival rates for this patient population. Those eligible in...
Posted 2 years ago by Wales Gene Park
The primary objectives of this study are: To confirm the safety and tolerability of magrolimab monotherapy in a relapsed/refractory (R/R) acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) population, and of magrolimab in combination with azacitidine in previously untreated participants with AML or MDS and participants with R/R AML and MDS To evaluate the efficacy of magrolimab monotherapy in R/R AML/MDS, and of magrolimab in combination with azacitidine in previously untreated participants with AML/MDS, or R/R AML/MDS as measured by complete remission (CR) rate for participants with AML and higher-risk MDS, and duration of complete response for participants with AML and higher-risk MDS, and duration of CR for participants with AML and higher-risk MDS To evaluate the safety, tolerability, and efficacy of magrolimab monotherapy or combination with azacitidine in low-risk MDS participants as measured by red blood cell (RBC) transfusion independence rate
Posted 1 year ago by Wales Gene Park
Brief Summary OxPLoreD is an observational cohort study to identify clinical, genomic and immunological predictive markers of progression to malignant disease. Open to individuals diagnosed in the last 3 years with high count MBL, Binet Stage A CLL, Immunoglobulin G/A/M (IgG, IgA, IgM) MGUS, asymptomatic WM not requiring treatment and smouldering myeloma not requiring treatment. Detailed Description The purpose of the study is to monitor patients with early stage lymphoproliferative disorders not meeting criteria for treatment, including early stage Chronic Lymphocytic Leukaemia (CLL), Monoclonal B-cell Lymphocytosis (MBL), Monoclonal Gammopathy of Uncertain Significance (MGUS), asymptomatic Waldenstroms Macroglobulinaemia (WM) and Smouldering Myeloma (SM). Each of these disorders has a pre-cancerous phase when abnormalities can be seen in the blood, however treatment may not be required. A minority of people with early stage lymphoproliferative disorders will go on to need treatment for blood or bone marrow cancer. Currently the investigators do not have...
Posted 10 months ago by Wales Gene Park
Brief Summary: A Phase 3, randomized, blinded study comparing pelabresib (CPI-0610) and ruxolitinib with placebo and ruxolitinib in myelofibrosis (MF) patients that have not been previously treated with Janus kinase inhibitors (JAKi). Pelabresib is a small molecule inhibitor of bromodomain and extra-terminal (BET) proteins.
Posted 2 years ago by Wales Gene Park
The purpose of this study is to test the safety and efficacy of AUTO4 a CAR T cell treatment targeting TRBC1 in patients with relapsed or refractory TRBC1 positive selected T-Non-Hodgkin Lymphoma.
Posted 2 years ago by Wales Gene Park
This study will evaluate a new maintenance therapy with the aim of improving the outcome of patients with acute myeloid leukaemia (AML) and myelodysplasia (MDS) after stem cell transplantation.
Posted 10 months ago by Wales Gene Park
Brief Summary: A phase III, randomised, open-label, Multicenter International Trial comparing ruxolitinib with either HydRoxycarbamIDe or interferon Alpha as first-line ThErapy for high-risk polycythemia vera (MITHRIDATE) Detailed Summary: The interventions are Arm A: Ruxolitinib and Arm B: Best Available Therapy (Hydroxycarbamide OR Interferon Alpha, any formulation permitted), which will be selected by the Investigator prior to randomisation. Randomisation will be in a 1:1 ratio and will be performed using a bespoke computer randomisation system developed by the Cancer Research UK Clinical Trials Unit (CRCTU) employing a stratified minimisation method. Patients will be stratified by: 1. Country of Origin: UK, France 2. Elected standard of care therapy: IFN, HC 3. Age: <60, ≥ 60 4. Prior thrombosis: No, Yes 5. Length of time from diagnosis: <5: ≥5 years 6. Cardiovascular risk factors, (including the following: arterial hypertension, diabetes, dyslipidemia, tobacco use, obesity): No, Yes Randomisation will be in a 1:1...
Posted 1 year ago by Wales Gene Park
Brief Summary Phase 1/2 study to determine safety, tolerability, pharmacokinetics, and anti-leukemic activity of Vodobatinib (K0706) in treatment-refractory/intolerant CML Detailed Description Part A ( for Healthy volunteers) of the study is completed Part B dose-escalation study is completed. Recruitment in dose-expansion is ongoing in India and Korea Part C study in subjects with treatment-refractory/intolerant is enrolling globally.
Posted 1 year ago by Wales Gene Park
Brief Summary Phase 1/2 study to determine safety, tolerability, pharmacokinetics, and anti-leukemic activity of Vodobatinib (K0706) in treatment-refractory/intolerant CML Detailed Description Part A ( for Healthy volunteers) of the study is completed Part B dose-escalation study is completed. Recruitment in dose-expansion is ongoing in India and Korea Part C study in subjects with treatment-refractory/intolerant is enrolling globally.
Posted 2 years ago by Wales Gene Park
The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics, and efficacy of ponatinib in children aged 1 to < 18 years with advanced leukemias, lymphomas, and solid tumors.
Posted 1 year ago by Wales Gene Park
Brief Summary The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics, and efficacy of ponatinib in children aged 1 to < 18 years with advanced leukemias, lymphomas, and solid tumors.
Posted 1 year ago by Wales Gene Park
Brief Summary The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics, and efficacy of ponatinib in children aged 1 to < 18 years with advanced leukemias, lymphomas, and solid tumors.
Posted 2 years ago by Wales Gene Park
The purpose of this first in human study is to assess safety, tolerability, Pharmacokinetic (PK) and preliminary clinical activity and to estimate the Maximum Tolerated Doses (MTD(s))/ Recommended Phase 2 Doses (RP2D(s)) of S65487 as single agent administered intravenously (i.v.) in adult patients with refractory or relapsed Acute Myeloid Leukemia (AML), Non-Hodgkin Lymphoma (NHL), Multiple Myeloma (MM) or Chronic Lymphocytic Leukemia (CLL).