Essential Thrombocythemia

Researchers are studying the use of unlicensed cryopreserved cord blood units CBUs for transplantation in both children and adults with blood cancers and other related disorders. This observational study involves patients with hematologic malignancies and various inherited and acquired disorders affecting the blood and immune system. The main goal is to monitor how well neutrophil recovery occurs after transplantation using these unlicensed CBUs in multiple institutions. Participants receive unlicensed cryopreserved CBUs as part of their transplant treatment. The study includes patients of any age receiving these CBUs for approved indications. The protocol focuses on the access and distribution of these unlicensed units rather than a specific treatment intervention. The study gathers data from recipients who receive these CBUs, tracking outcomes after transplantation. Participants are monitored for neutrophil recovery at 60 and 100 days after transplant, defined by a neutrophil count of at least 500mm3. Researchers also collect information on infection transmission, infusion reactions, survival rates at one year, and incidence of acute and chronic graft versus host disease. Platelet recovery is also evaluated. Safety and efficacy outcomes are followed over time to better understand the effects of unlicensed CBUs in this patient population.

Researchers are evaluating IM-1021, an antibody-drug conjugate, in a Phase 1 study involving participants with advanced B-cell lymphomas and solid tumors. This first-in-human, open-label study aims to assess the safety, tolerability, pharmacokinetics, and preliminary anti-tumor activity of IM-1021. The study includes a dose escalation phase to find safe and tolerable doses and an expansion phase to further evaluate these doses in specific cancer types. The study has two parts Part A focuses on escalating doses of IM-1021 given intravenously to determine safety and recommended dosing schedules, including the possibility of alternative dosing. Part B involves expanding participant groups to further test safety and early effectiveness of IM-1021 at doses chosen from Part A. Participants receive the study drug intravenously on an intermittent basis throughout these phases. Participants will undergo multiple assessments including monitoring for treatment-related adverse events, pharmacokinetic blood tests, and evaluations of anti-tumor effects from week 6 until disease progression or study discontinuation. Safety and tolerability will be tracked from the first dose until about 37 days after the last dose. The study duration spans from screening, treatment, and follow-up with data collection continuing up to the study end in 2029.

Researchers are evaluating cytokine induced memory-like natural killer CIML NK cells combined with IL-2 in patients aged 12 years and older who have Acute Myeloid Leukemia AML, Myelodysplastic Syndromes MDS, Myeloproliferative Neoplasms MPN, or Juvenile Myelomonocytic Leukemia JMML that returned after stem cell transplantation. This Phase I clinical trial aims to test the safety and find the appropriate dose for this investigational treatment, which has not been approved by the FDA for relapsed disease. Participants receive intravenous infusions of CIML NK cells on day 0. Before this, patients are given chemotherapy drugs fludarabine daily for three doses starting on day -5 and cyclophosphamide on days -5 and -4 to prepare the body. The study includes both adult and pediatric patients who have relapsed after haploidentical or HLA-matched stem cell transplants. The treatment is followed for safety and response over several weeks. During the study, participants will be monitored closely for safety for six weeks and assessed for treatment response after 28 days. Further follow-ups include checking for leukemia-free survival and overall survival at 100 days and one year, as well as monitoring for acute and chronic graft-versus-host disease over several months to one year. The trial involves regular evaluations including bone marrow tests, blood tests, and clinical assessments to track disease status and side effects throughout participation.

Researchers are comparing INCA033989 with the best available therapy for adults who have essential thrombocythemia ET with a CALR mutation and have previously received cytoreductive treatment. The study aims to evaluate the effects of these treatments on this specific patient group. It is a Phase 3 clinical trial sponsored by Incyte Corporation to assess treatment responses and safety. Participants will be randomly assigned to receive either INCA033989 administered intravenously or the best available therapy chosen by their doctor. The treatments are given according to the study protocol. The study focuses on treatment outcomes over a period of weeks, including response durability and symptom changes, with assessments at specified timepoints. During the study, participants will have regular visits to monitor their clinical and hematologic responses, symptoms, and any side effects. Researchers will collect data on mutation levels, symptom questionnaires, and fatigue assessments up to 48 weeks. Safety monitoring will continue for 60 days following the last dose. The total duration of participation may extend up to several months as outlined by the trial schedule.

Researchers are evaluating drug combinations to prevent graft-versus-host disease GVHD in people who have received stem cell transplants from unrelated donors with different blood types. This platform protocol focuses on safety and effectiveness of post-transplant cyclophosphamide PTCy based GVHD prevention after mismatched unrelated donor hematopoietic cell transplants in patients with malignant blood diseases. The study compares new drug combinations to a standard treatment. Participants receive one of the drug combinations after transplant, including investigational arms named ACCEL-001 and ACCEL-002, or the shared comparator control group. Conditioning regimens vary and may include combinations of drugs such as busulfan, fludarabine, melphalan, cyclophosphamide, and total body irradiation before transplant. The donor stem cell graft infusion occurs on Day 0, followed by specific post-transplant medications like cyclophosphamide, tacrolimus, mycophenolate mofetil, abatacept, and ruxolitinib, with supportive care for infection prevention and other complications. During the study, participants have regular doctor visits for check-ups and routine tests, complete surveys on physical and emotional health, and provide blood and stool samples. Researchers monitor outcomes including graft-versus-host disease-free, relapse-free survival one year after transplant, infection rates, survival, graft failure, and immune recovery. Safety is closely tracked, including monitoring for cytokine release syndrome and infections. The study lasts for at least one year post-transplant, with detailed data collection on treatment response and side effects.

Researchers are studying the treatment of accelerated or blast phase Philadelphia chromosome-negative myeloproliferative neoplasms MPNs, a type of blood cancer, by comparing two drug regimens. This phase II trial evaluates whether combining ASTX727, which includes the drugs cedazuridine and decitabine, with iadademstat is more effective than ASTX727 alone. ASTX727 works by helping bone marrow produce normal blood cells and attacking abnormal ones, while iadademstat may stop tumor growth by blocking enzymes needed for cell growth. Patients are randomly assigned to one of two treatment groups. One group takes ASTX727 orally once daily for five days in a 28-day cycle. The other group takes ASTX727 on the same schedule plus iadademstat orally on days 1-5, 8-12, 15-19, and 22-26 of each 28-day cycle. Treatment cycles continue unless the disease progresses or side effects are unacceptable. During the study, patients provide buccal swabs, blood samples, and bone marrow samples for analysis. Participants are monitored throughout treatment with various tests including blood and bone marrow examinations. After stopping treatment for reasons other than disease progression, patients have follow-up visits every three months if they stop due to progression, follow-up occurs every six months. Researchers measure the rate of complete acute leukemia response within four treatment cycles and track event-free survival, overall survival, and stem cell transplantation rates over up to two years.

Researchers are evaluating the safety, tolerability, pharmacokinetics, and preliminary effectiveness of BL-M24D1 in patients with relapsed or refractory multiple myeloma and other blood cancers. This open, multicenter, non-randomized Phase I clinical trial aims to gather early data on how this investigational drug behaves and affects patients who have limited treatment options after standard therapies have failed or are unavailable. The study has two parts a dose escalation phase Phase Ia and an expansion cohort phase Phase Ib. Participants receive BL-M24D1 through intravenous infusion over a 2-week cycle. If clinical benefit is observed, patients may continue receiving additional cycles until disease progression, intolerable side effects, or other reasons lead to stopping treatment. During the trial, participants undergo regular assessments including monitoring for dose-limiting toxicities within 28 days after the first dose and evaluation of the maximum tolerated dose. Over approximately 24 months, researchers will track treatment-emergent side effects, pharmacokinetic measures like drug concentration and clearance, immune responses to the drug, and clinical responses such as objective response rate and duration of response. The study includes safety follow-up and long-term monitoring.

Researchers are evaluating GLB-001, an oral drug, in patients with relapsed, refractory, or intolerant myeloid malignancies including polycythemia vera, essential thrombocythemia, myelofibrosis, various myelodysplastic syndromes, and acute myeloid leukemia. This phase 1, open-label study aims to assess the safety, tolerability, how the drug moves through and affects the body, and early signs of efficacy. The study includes three parts dose escalation, dose exploration, and dose expansion to find the best dose for future studies. The study involves giving GLB-001 orally to participants in three phases. Phase 1a uses a dose-escalation design to evaluate safety and tolerability in patients with polycythemia vera or essential thrombocythemia. Phase 1b also uses dose escalation to study safety in patients with myelofibrosis, myelodysplastic syndromes, and acute myeloid leukemia. Phase 1c expands dosing to further assess tolerability, efficacy, and to select the recommended dose for phase 2 trials. Dose levels and treatment schedules are adjusted based on participant response and safety. Participants will undergo assessments to monitor dose-limiting toxicities within 28 days of the first dose and longer-term safety up to three years. Researchers will evaluate drug levels in the body and clinical responses to treatment over periods ranging from weeks to years depending on the disease type and study phase. Major organ functions, blood tests, adverse events, and response to treatment will be closely monitored throughout the study. Participants must agree to follow the visit schedule and study requirements during their involvement.

Researchers are evaluating two different approaches to prevent chronic graft-versus-host disease GVHD in people with blood cancers who are receiving allogeneic hematopoietic stem cell transplantation allo-HCT. The study aims to determine which prevention method is more effective at reducing chronic GVHD up to one year after transplantation. This is a phase 2 clinical trial focused on prevention in this patient population. Participants will receive one of two regimens an experimental group receiving an intermediate dose of post-transplant cyclophosphamide PTCY combined with tacrolimus, mycophenolate mofetil MMF, and the drug ruxolitinib taken twice daily or a standard group receiving a full dose of PTCY with tacrolimus and MMF. Tacrolimus dosing starts on day 5 after transplant, with tapering schedules depending on the group. MMF is given from day 5 to day 35. The study compares these two approaches for preventing chronic GVHD. During the study, participants will be monitored up to one year after transplant to assess chronic GVHD-free survival as the primary outcome. Researchers will also track the incidence of moderate to severe infections over one year. Safety, treatment adherence, and clinical responses will be evaluated through routine medical visits and assessments during this period. The total participation time spans the transplant procedure and one year of follow-up.

Researchers are studying the effects of multiple doses of venetoclax on how the body processes ethinyl estradiol and levonorgestrel in female participants who have various types of blood cancers, specifically different subtypes of non-Hodgkins lymphoma. This Phase 1 trial aims to understand the pharmacokinetics of these drugs when given together to help guide treatment decisions. Participants receiving clinical benefit without disease progression may continue venetoclax treatment in a separate extension study. The study involves administering ethinyl estradiollevonorgestrel tablets on the first day of the first and third periods, while venetoclax tablets are given starting on the first day of the second period and then daily thereafter. This design allows researchers to evaluate the interaction between the drugs over approximately 59 days after the initial dose. The trial does not include masking or placebo controls. During the study, participants undergo monitoring to measure key drug parameters such as the time to reach maximum concentration Tmax, maximum concentration Cmax, half-life t12, and overall drug exposure AUC for both venetoclax and ethinyl estradiollevonorgestrel. These assessments help understand how the drugs behave in the body. Safety and disease status are also monitored, and participants may continue treatment in an extension phase if benefiting from the therapy. The total study duration includes follow-up up to about 59 days after the initial dose.