Clinical Research Directory

Maintenance Treatment With Imetelstat in Patients With High-Risk Myeloid Neoplasms After Allo-SCT

The purpose of this clinical trial is to learn if imetelstat is safe to use in participants with high-risk myeloid malignancies who have received an allogenic hematologic stem cell transplantation (allo-SCT). Participants will receive imetelstat by intravenous infusion once every 28 days for up to one year.

A Study to Investigate APL-4098 Alone and in Combination in Adults With AML or MDS

This is an open-label, Phase 1 study to determine the safety, tolerability, and efficacy of APL-4098 alone, and in combination with azacitidine, and in combination with azacitidine plus venetoclax for the treatment of acute myeloid leukemia (AML), myelodysplastic syndrome (MDS)/AML and MDS-excess blasts (EB).

CLL-1/CD70 Dual-Target CAR-T Cell Therapy for Acute Myeloid Leukemia

This is a single-center, open-label, single-arm, prospective, investigator-initiated dose-escalation study to evaluate the safety, tolerability, and preliminary efficacy of an autologous CLL-1/CD70 dual-target CAR-T cell injection in patients with relapsed or refractory (R/R) acute myeloid leukemia (AML; acute promyelocytic leukemia excluded). After leukapheresis for CAR-T cell manufacture, participants receive lymphodepleting conditioning (fludarabine 30 mg/m\^2/day plus cyclophosphamide 300 mg/m\^2/day on Days -5 to -3), followed by a single intravenous infusion of CLL-1-CD70 CAR-T cells. Dose escalation follows a traditional 3+3 design with planned dose levels of 0.5 x 10\^6, 1 x 10\^6, and 2 x 10\^6 CAR-T cells/kg, guided by dose-limiting toxicities (DLTs) assessed during Days 1-28 after infusion. The primary endpoint is safety and tolerability, as assessed by treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs), including cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), hematologic toxicity, organ toxicity, infections, hemophagocytic lymphohistiocytosis/macrophage activation syndrome (HLH/MAS), and tumor lysis syndrome (TLS). Efficacy will be evaluated by the composite complete remission rate (CRc, defined as the proportion of patients achieving CR, CRh, or CRi) at prespecified time points according to the European LeukemiaNet (ELN) 2022 criteria, overall survival (OS), event-free survival (EFS), duration of response (DOR), and cumulative incidence of relapse (CIR) over a 1-year follow-up period. Immune reconstitution following CAR-T cell infusion will also be assessed at prespecified time points. CAR-T cellular kinetics in peripheral blood (CAR transgene copies, Cmax, Tmax, and AUC0-28d) will also be evaluated.

Pyronaridine in Acute Myeloid Leukemia (AML)

A Phase 2a clinical trial on up to n=200 male and female subjects 18 years and over who were diagnosed with acute myeloid leukemia (AML) or acute lymphoblastic leukemia (ALL). Subjects are randomised in approximately a 1:1 ratio to receive standard of care treatment plus either pyronaridine (PND) or placebo. Quality of life parameters are measured. Visits include physical examinations, and blood draws for complete blood count with differential (CBC) and complete metabolic panel (CMP). Survival of subjects is tracked in Year 2.

A Study of Cladribine, Low Dose Cytarabine, and Venetoclax in Treatment of Relapsed/Refractory or Secondary Acute Myeloid Leukemia

Acute myeloid leukemia (AML) is a bone marrow cancer that is challenging to treat. It is the most common type of acute leukemia, particularly in adults. There are around 20,000 cases of acute myeloid leukemia diagnosed in the United States every year. Despite the recent significant progress in the understanding of acute myeloid leukemia leading to the development of new therapies, significant challenges remain. The initial treatment for acute myeloid leukemia involves using therapies aimed at reducing the disease burden in the bone marrow to the lowest possible level (a state known as disease remission). This is usually followed by consolidation treatment aimed at curing the disease. The initial treatment involves high intensity chemotherapy in younger adults who can tolerate these therapies and low intensity therapies for older adults or those with other medical conditions that prohibit them from receiving high intensity chemotherapy. The consolidation therapy involves either more chemotherapy or a bone marrow transplant. In the recent years, a treatment regimen consisting of two drugs; Azacytidine and Venetoclax has become the standard of care for low intensity therapy intended for older adults. Despite significant improvement in outcomes of acute myeloid leukemia in older adults after the introduction of Azacytidine/Venetoclax, yet 40% of patients who receive this treatment will either be refractory to it or relapse after an initial remission. Those whose leukemia relapses after Azacytidine/Venetoclax treatment are left with very few treatment options and have a dismal prognosis. Based on previous laboratory studies, certain subtypes of acute myeloid leukemia tend to not respond as well to Azacytidine/Venetoclax therapy and have a better chance of responding to the treatment regimen the investigators are proposing in this study. The study treatment regimen consists of 3 drugs; Cladribine, low dose Cytarabine and Venetoclax. Demonstrating efficacy of the study regimen in treatment of relapsed/refractory acute myeloid leukemia, after prior Venetoclax therapy, will provide another treatment option for those with a relapsed/refractory disease who wish to continue receiving therapy.

A Study of Venetoclax in Combination With Low Dose Cytarabine Versus Low Dose Cytarabine Alone in Treatment Naive Patients With Acute Myeloid Leukemia Who Are Ineligible for Intensive Chemotherapy

The primary objective of this study is to evaluate if venetoclax when co administered with low-dose cytarabine (LDAC) improves overall survival (OS) versus LDAC and placebo, in treatment-naïve patients with acute myeloid leukemia (AML).

A Study of Gilteritinib in Combination With Ivosidenib or Enasidenib in People With Acute Myeloid Leukemia (AML)

The researchers are doing this study to see if the combination of gilteritinib with ivosidenib or enasidenib is a safe and effective treatment for people with relapsed/refractory AML with FLT3/IDH1 or FLT3/IDH2 gene mutations. The researchers will also look for the highest dose of the combination of gilteritinib with ivosidenib or enasidenib that causes few or mild side effects. When the highest safe dose is found, they will test that dose in new groups of participants.

Niclosamide in Pediatric Patients With Relapsed and Refractory AML

Protocol is designed to evaluate a niclosamide dose escalation scale in combination with cytarabine as a therapeutic modality for pediatric subjects with relapsed/refractory acute myeloid leukemia.

Improving Delivery of Aging-Related Supportive Care for Older Adults With Acute Myeloid Leukemia

The goal of this clinical trial is to test a way of delivering supportive care to adults 60 years and older who are starting venetoclax-based treatment for newly diagnosed acute myeloid leukemia (AML). Older adults with AML often have aging-related needs, such as problems with mobility, nutrition, mood, memory, or medications, that are not always addressed in a consistent way. In this study, a health questionnaire and short in-person checks (a geriatric assessment) are used to find these needs early, and matching supportive care orders are prepared in the electronic health record and sent to the treating doctor, who decides whether to place each one. This approach is called Active Default. The main questions the study aims to answer are: * How often are the prepared supportive care orders signed by treating doctors (implementation fidelity)? * Can each step of the process, from completing the assessment to receiving supportive care services, be carried out as planned? Participants will: * Complete questionnaires and short in-person checks of walking, balance, strength, memory, mood, and medications at the start of treatment * Receive supportive care services (for example physical therapy, nutrition, or social work) if their doctor approves the prepared orders * Answer phone check-ins over 90 days and repeat two short checks at about two months * Be invited to one optional interview about their experience Healthcare providers involved in participants' care will be invited to complete a one-time survey and an optional interview about the approach.

Studies to Assess Ziftomenib in Combination With Ven+Aza or 7+3 in Patients With Untreated NPM1-m or KMT2A-r AML

Ziftomenib is an investigational drug in development for the treatment of patients with acute myeloid leukemia (AML) with eligible genetic alterations. Ziftomenib is a type of therapy known to target the menin pathway in cancer cells. This protocol has 2 separate studies that will investigate the benefits and risks of adding ziftomenib to standard-of-care (SOC) AML treatments in patients with certain genetic mutations who have not received any treatment for their AML. In the first study, the Nonintensive Therapy Study, older patients or those with serious medical problems will receive the SOC therapies venetoclax (ven) and azacitidine (aza), plus either ziftomenib or a placebo. In the second study, the Intensive Therapy Study, medically fit patients will receive (a) the SOC therapies cytarabine and daunorubicin, plus either ziftomenib or a placebo during a first treatment phase called induction, (b) cytarabine plus either ziftomenib or a placebo during a second treatment phase called consolidation, and (c) ziftomenib or a placebo during a third treatment phase called maintenance. The physician will determine which study is the appropriate treatment for the patient, but neither the patient nor their physician will know whether the patient has been assigned to receive ziftomenib or a placebo. This design is called "double-blinded".

Luveltamab Tazevibulin (STRO-002) in Infants and Children < 12 Years of Age With Relapsed/Refractory CBFA2T3::GLIS2 AML

This trial will evaluate whether luveltamab tazevibulin is well tolerated and active against a rare form of AML carrying a particular genetic abnormality called CBFA2T3::GLIS2 that arises in infants and children. To be treated in this trial children must have a leukemia which did not respond or recurred after prior treatment. Luveltamab tazevibulin is an antibody-drug conjugate, which brings tazevibulin, an anticancer drug, to a molecule called FOLR1, present on the surface of CBFA2T3::GLIS2 AML cells.

Biomarkers in Patients With Anemia-Induced Thrombocytopenic Bleeding

This pilot study aims to gather preliminary evidence on how different hemoglobin levels impact blood biomarkers related to bleeding. The feasibility of conducting a future larger clinical trial will also be assessed. Red blood cell transfusions are part of the standard of care for patients with leukemia. This study evaluates two transfusion strategies: one that maintains hemoglobin levels above the standard-of-care threshold, reflecting current routine practice; and another that maintains hemoglobin levels above 110 g/L, which is closer to the normal hemoglobin range. The normal hemoglobin range is 120-160 g/L for females and 140-180 g/L for males. Raising hemoglobin levels closer to normal values may reduce bleeding risk.

Efficacy of Hypomethylating Agents vs. Intensive Chemotherapy in Acute Myeloid Leukemia Using 5hmC as a Blood-Based Minimal Residual Disease Marker

This is a therapeutic intervention trial evaluating the clinical utility of a novel blood-based epigenetic biomarker-genome-wide 5-hydroxymethylcytosine (5hmC) in cell-free DNA (cfDNA)-for assessing measurable residual disease (MRD) in patients with newly diagnosed acute myeloid leukemia (AML). The study compares the efficacy of hypomethylating agent (HMA)-based therapy versus intensive induction chemotherapy, using the 5hmC biomarker to guide post-induction treatment decisions. Approximately 112 adult patients will be enrolled and assigned to treatment arms based on a stratified sampling scheme. Blood samples will be collected at defined intervals to assess MRD status. Primary endpoints include minimal residual disease (MRD) negativity rate, duration of remission, event-free survival (EFS), and overall survival (OS).

Monitoring, Detoxifying, and Rebalancing Metals During Acute Myeloid Leukemia (AML) Therapy, a Phase 2 Randomized Study

The goal of this clinical research study is to learn if metal detoxification (with calcium disodium edetate \[Ca-EDTA\] and dimercaptosuccinic acid \[DMSA\]) during standard therapy can help improve outcomes in patients with intermediate-risk, high-risk, or secondary AML compared to standard therapy alone. Researchers think lowering the level of metals found in the blood/bone marrow may help to control the disease and/or improve the response to chemotherapy.

Darzalex Faspro (Daratumumab and Hyaluronidase-fihj) Before Standard Desensitization and Allogeneic Bone Marrow or Peripheral Blood Stem Cell Transplantation in Adult Patients at High-risk for Primary Graft Failure Secondary to Donor Specific Antibodies

This research is being done to investigate the safety and effectiveness of Darzalex Faspro (daratumumab and hyaluronidase-fihj) (a monoclonal antibody that targets plasma cells that make antibodies) and whether it can lower donor specific antibodies (DSA) levels to low enough levels to permit patients to proceed with allogeneic peripheral blood transplant (alloBMT). Those being asked to participate have high DSA levels that puts those being asked to participate at high risk of rejecting the available donor's blood stem cells and making those being asked to participate ineligible to receive a stem cell transplant.

Ivosidenib as Post-HSCT Maintenance for AML

This is a Phase 2 study of the study drug, ivosidenib (a mutant IDH1 inhibitor), compared to placebo, given to patients with IDH1-mutant acute myeloid leukemia (AML) after hematopoietic stem cell transplantation (HCT).

CLL-1-Targeted In Vivo CAR-T Cell Immunotherapy for Relapsed/Refractory Acute Myeloid Leukemia

This is a single-center, open-label, single-arm, phase 1 dose-escalation study to evaluate the safety, tolerability, preliminary efficacy, and cellular kinetics of SL1CC Injection, an in vivo CAR-T therapy targeting CLL-1, in patients with relapsed or refractory acute myeloid leukemia (R/R AML; acute promyelocytic leukemia excluded). SL1CC Injection is administered as a single intravenous infusion without lymphodepleting conditioning. Dose escalation follows a traditional 3+3 design with planned dose levels of 1 × 10\^9, 3 × 10\^9, and 6 × 10\^9 transducing units (TU), guided by the occurrence of dose-limiting toxicities (DLTs). Treatment-emergent adverse events and serious adverse events, including cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), hematologic toxicity, organ toxicity, and other immune therapy-related toxicities, will be assessed. Preliminary antitumor activity, assessed by composite complete remission (CR/CRi) and measurable residual disease (MRD) status according to the European LeukemiaNet (ELN) 2022 criteria, and the expansion and persistence of CAR-T cells in peripheral blood will also be evaluated.

Effectiveness and Safety of ONUREG (Oral Azacitidine) in Chinese Patients With Acute Myeloid Leukemia

The purpose of this study is to assess real-world effectiveness and safety of oral azacitidine in adults diagnosed with acute myeloid leukemia (AML) in Hong Kong

A Study of Pevonedistat and Venetoclax Combined With Azacitidine to Treat Acute Myeloid Leukemia (AML) in Adults Unable to Receive Intensive Chemotherapy

The main aim is to see how the combination of pevonedistat + venetoclax + azacitidine compares to venetoclax + azacitidine in adults recently diagnosed with AML who are unable to be treated with intensive chemotherapy. Participants will receive either pevonedistat + venetoclax + azacitidine or venetoclax + azacitidine in 28-day treatment cycles. Bone marrow samples (biopsy) will be collected throughout the study. Pevonedistat will be given as an intravenous (IV) infusion and Azacitidine will be given through IV or subcutaneous (under the skin). Study treatments may continue as long as the participant is receiving benefit from it. Participants may choose to stop treatment at any time.

Liposomal Mitoxantrone Plus Azacitidine and Venetoclax in Newly Diagnosed Elderly or Unfit AML

This prospective, open-label, multicenter phase Ib trial will evaluate the safety, tolerability, and RP2D of the VAM regimen (liposomal mitoxantrone + azacitidine \[AZA\] + venetoclax \[VEN\]) in elderly or unfit patients with newly diagnosed AML. A standard 3+3 dose escalation will enroll 12-30 patients, testing liposomal mitoxantrone at 8, 12, 16, and 20 mg/m². VEN duration (9 vs. 14 days) will be determined at the 8 mg/m² dose level, after which only liposomal mitoxantrone will be escalated while AZA and VEN will remain fixed. Induction therapy will consist of up to two 28-day cycles. Responders achieving CR/CRi/MLFS will be eligible for up to 4 consolidation cycles (total ≤6 cycles), after which they will proceed to maintenance with either AZA+VEN or observation.

Safety and Efficacy of RVU120 for Treatment of Relapsed/Refractory AML

The goal of this study is to assess the safety, tolerability, anti-tumor activity (efficacy), pharmacokinetics (PK), and pharmacodynamics (PD) of the agent RVU120 when administered to adult patients with relapsed or refractory acute myeloid leukemia (AML) or relapsed or progressing high-risk myelodysplastic syndrome (HR-MDS) and who have no alternative therapies available. The study consists of two parts. Part 1 will assess the safety and tolerability of the dosages given and the level of anti-tumor activity or clinical response. Based on the results from part 1 the study will continue to enrol patient into Part 2 which will continue to evaluate safety and tolerability and anti-tumor activity in a larger number of patients.

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.

Monocentric Phase 1 Study With Escalation of Doses of Tocilizumab in Combination With Chemotherapy (Idarubicin and Cytarabine) in Patients With Acute Myeloblastic Leukemia (AML)

This is a phase 1 dose escalation study testing the addition of an anti-IL6 (tocilizumab) to standard induction chemotherapy for high-risk AML.

A Study of Gilteritinib, Venetoclax and Azacitidine as a Combined Treatment for People Newly Diagnosed With Acute Myeloid Leukemia

People with acute myeloid leukemia (AML) are usually treated with chemotherapy. Some people with AML have a changed FLT3 gene which causes leukemia cells to grow faster. Therefore, chemotherapy is less suitable to treat AML in people with the changed FLT3 gene. Gilteritinib, given with venetoclax and azacitidine, is a potential new treatment for people with AML with the changed FLT3 gene. They cannot have chemotherapy due to old age or other conditions. Before these combined 3 medicines are available as a treatment, the researchers need to understand how they are processed by and act upon the body when given together. In this study, they do this to find a suitable dose for venetoclax and to check for potential medical problems from the treatment. In this study, people newly diagnosed with AML who have the changed FLT3 gene and cannot have chemotherapy can take part. The main aims of this study are: to find suitable doses of gilteritinib, venetoclax and azacitidine as a combined treatment; to learn how they are processed by and act upon the body; to learn the remission rate; to check for medical problems during this treatment. In the study, people will visit the study clinic many times. The first visit is to check if they can take part. People will be asked about their medical history, have a medical examination, and have their vital signs checked. Also, they will have an ECG to check their heart rhythm and have some blood and urine samples taken for laboratory tests. They will have a chest X-ray and a bone marrow sample will be taken. The changed FLT3 gene will be confirmed, either by the bone marrow or a blood sample. This study will be in 2 phases. In Phase 1, different small groups of people will take venetoclax tablets containing lower to higher doses in the combined treatment. The doses of gilteritinib and azacytidine will be unchanged. This is done to find a suitable dose of venetoclax to use in phase 2 of the study. People will take tablets of gilteritinib and venetoclax once a day on a 28-day cycle. They will be given azacytidine as an infusion or an injection just under the skin. This will be for 7 days at the beginning of each 28-day cycle. They will continue cycles of treatment throughout this phase of the study. In Phase 2, more people newly diagnosed with AML with the changed FLT3 gene will take part. They will be treated with the suitable doses of the combined treatment worked out from Phase 1. Treatment will be on a 28-day cycle. People will continue on cycles of treatment throughout this phase of the study. Researchers will work out the remission rate from this phase of the study. In each phase of the study, people can continue with up to 12 cycles of treatment if they can manage any medical problems. People will visit the study clinic many times during their first treatment cycle, and less often during the next cycles. During these visits, medical problems will be recorded and some blood samples will be taken for laboratory tests. On some visits, people will also have their vital signs checked. Bone marrow samples will be taken during cycle 1, and at the beginning of cycle 3. More samples will be taken during the study from people who are not in remission. When people have finished treatment, those who have responded well to treatment and are in remission will be invited to continue with up to 24 more cycles of gilteritinib plus azacitidine. All people taking part in the study will visit the study clinic for an end-of-treatment visit. During this visit, medical problems will be recorded and some blood samples will be taken for laboratory tests. People will have a medical examination, an ECG, and will have their vital signs checked. Also, a bone marrow sample will be taken. There will be a follow-up visit 30 days later to check for medical problems. Then people will visit the clinic or get a phone call every 3 months for up to 3 years. This is to give an update on their current treatment for AML. Some people can have a stem cell transplant during the study if they meet certain study rules. They will pause their study treatment during the stem cell transplant process and continue study treatment afterwards.