AML (Acute Myeloid Leukemia)

Purpose/Specific Aims The study will determine if there is a reduction in malignant cell burden when patients with relapsed and/or refractory acute myeloid leukemia (AML) or multiple myeloma (MM) consume tea made from the dried leaves of Annona muricata (Soursop). The study goal is to determine the safety and anti-neoplastic efficacy of Annona muricata tea when taken in escalating frequency over a period of 21 days by patients with relapsed/refractory AML or MM for whom there are no standard therapeutic options.

A open-label drug-drug interaction (DDI) study to evaluate the effects of olutasidenib on the pharmacokinetics (PK) of a CYP450 and OATP1B1 probe substrate cocktail in participants with IDH1 mutation-positive malignancies.

The goal of this study is to evaluate the safety of CHM-029, an investigational oral medicine, and to evaluate its activity in treating certain types of acute myeloid leukemia (AML) in adults. The main questions the study aims to answer are: * What is an appropriate dose of CHM-029? * What side effects may occur with CHM-029? * How does the body process CHM-029? Researchers will evaluate increasing dose levels of CHM-029 to better understand its safety and how the body responds to treatment. Participants will visit the study clinic regularly for safety assessments, blood tests, electrocardiograms (ECGs), and bone marrow evaluations to monitor their health and response to treatment.

Acute myeloid leukaemia (AML) is a clonal haematological malignancy characterised by arrested myeloid differentiation and uncontrolled proliferation of blast cells in the bone marrow and peripheral blood. It is the most common acute leukaemia in adults and carries a high disease-related mortality. Globally, the median age of diagnosis is approximately 68 years; however, a significant proportion of patients are diagnosed below the age of 50 years, constituting the 'young fit' population for whom aggressive curative-intent therapy is most appropriate. The epidemiology of AML in South Asia and Pakistan remains incompletely characterised. Published single-centre and multi-centre data from Pakistan suggest that AML represents a major proportion of haematological malignancies presenting to tertiary centres. AFBMTC, as the largest haematology and transplant centre in Pakistan, has accumulated over 2,000 HSCT procedures since 2001 and has established the necessary infrastructure for prospective clinical research in this disease. Cytogenetic and molecular classification of AML profoundly influences prognosis and treatment decisions. The European LeukemiaNet (ELN) 2022 risk stratification framework categorises AML into Favourable, Intermediate, and Adverse risk groups based on chromosomal abnormalities and somatic mutations including NPM1, FLT3-ITD, IDH1/2, RUNX1, ASXL1, TP53, and others. This framework underpins post-remission pathway assignment in the current protocol.

The rationale to conduct this RWE study is to provide data to support the safety of CD34 selected grafts versus T replete PBSC transplants to address concerns about increased TRM in CD34 selected graft recipients.

A Phase 1b, open-label, multicenter, dose escalation and dose expansion study to evaluate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of intravenously (IV) administered CLN-049 in combination with azacitidine (Aza) and venetoclax (Ven) in patients with newly diagnosed (ND) AML.

Protocol Title: A Prospective, Randomized Controlled Study of Venetoclax Plus 3-Day Decitabine (DEC3-VEN) Versus Venetoclax Plus "2+6" DA Versus "3+7" DA Regimen in Adult Patients with Newly Diagnosed Acute Myeloid Leukemia (AML) Objective: This is a prospective, open-label, randomized, multicenter, phase II trial designed to compare the efficacy and safety of three induction regimens-Venetoclax plus 3-day Decitabine (DEC3-VEN), Venetoclax plus "2+6" DA, and standard "3+7" DA-in adult patients with newly diagnosed, intensifiable AML. Study Design: The study employs a prospective, randomized, controlled, multicenter design. A total of 291 eligible patients will be enrolled across approximately 10 centers in China and randomized in a 2:2:1 ratio to the three treatment arms. Key Eligibility Criteria: Inclusion: Aged 16-65 with newly diagnosed non-APL AML (excluding favorable CBF-AML), eligible for intensive chemotherapy, ECOG ≤2, and adequate organ function. Exclusion: Prior AML treatment, secondary AML, active severe infection, significant cardiac comorbidity, or known hypersensitivity to the study drugs. Interventions: Induction: Arm A (VEN+"2+6"DA): Venetoclax (D1-8), Daunorubicin (D2-3), Cytarabine (D2-7). Arm B (DEC3-VEN): Venetoclax (D1-14), Decitabine (D4-6). FLT3/ITD+ patients add Sorafenib or Gilteritinib (D8-14). Arm C ("3+7"DA): Daunorubicin (D1-3), Cytarabine (D1-7). Consolidation (2 cycles): Arms A/B: Venetoclax + Intermediate-Dose Cytarabine. Arm C: High-Dose Cytarabine. Consolidation (Subsequent cycles): All arms receive multiple cycles of DA or HA regimens. Maintenance (6-8 cycles): Arms A/B: Venetoclax + Azacitidine. Arm C: Azacitidine. Main Outcome Measures: Primary Endpoint: Composite Complete Remission Rate (CR + CRi) after induction. Secondary Endpoints: Overall Survival (OS), CR rate, MRD-negative rate, Relapse-Free Survival (RFS), Event-Free Survival (EFS), and safety. Keywords: Acute Myeloid Leukemia, Venetoclax, Decitabine, Consolidation Therapy, Maintenance Therapy, Randomized Controlled Trial.

This is a Phase 1, open label, dose-escalation study to evaluate the safety, expansion, persistence, and preliminary clinical activity of lentivirally transduced autologous T cells expressing anti-CD64 chimeric antigen receptors (CAR) expressing tandem CD3ζ and 4-1BB (CD3ζ/4-1BB) costimulatory domains in subjects with refractory or relapsed (R/R) acute myeloid leukemia (AML). This CAR T cell product will be referred to as "CD64 CAR T" which is CD64 directed, autologous, genetically modified CAR T cells. The primary objective of the study is to identify the safety profile and maximum tolerated dose (MTD) of CD64 CAR T in subjects with R/R AML as determined by the defined DLTs using a standard Bayesian Optimal Interval (BOIN) design.

This study aims to explore a superior first-line induction remission regimen by incorporating Chidamide into the modified VAH chemotherapy combined with targeted therapy regimen, leveraging its dual epigenetic modulation mechanism.

This study aims to investigate the clinical efficacy of haploidentical-cord blood hematopoietic stem cell transplantation in patients with acute myeloid leukemia (AML) and high-risk myelodysplastic syndromes (MDS), and to analyze the impact of different engraftment patterns (haploidentical engraftment versus cord blood engraftment) on clinical outcomes. By comparing the efficacy of haploidentical-cord blood transplantation in different subtypes of AML and MDS, this research will explore its unique advantages and comparative effectiveness relative to conventional transplantation strategies, so as to provide new evidence for clinical practice. Specific research objectives I. To evaluate the efficacy of haploidentical-cord blood hematopoietic stem cell transplantation for AML and high-risk MDS, including the speed of hematopoietic recovery, immune tolerance, and long-term survival rates. II. To compare the effects of different engraftment patterns (haploidentical engraftment vs. cord blood engraftment) on quality of life, immune tolerance, early complications, and long-term prognosis. III. To identify the clinical advantages and indications of haploidentical-cord blood transplantation through data analysis, and to provide a theoretical basis for clinical decision-making. Novelty of the Study I. Innovation in Hematopoietic Stem Cell Infusion Schedule The present study employs a sequential infusion strategy: haploidentical stem cells are infused on Day 0, and umbilical cord blood cells are infused on Day +6 after transplantation.In contrast to the conventional approach used at most domestic and international centers (including the uzhou Protocol), in which both stem cell sources are infused simultaneously on Day 0, the current protocol delays cord blood infusion. This design confers potential advantages for immune reconstitution and long-term cord blood engraftment. II. Unique Myeloablative Conditioning Regimen The conditioning regimen used in this study is as follows: Fludarabine 25 mg/m² for 5 days, Cytarabine 2 mg/m² for 5 days, intravenous Busulfan 3.2 mg/kg for 3 days, ATG 5 mg/m² for 2 days, Melphalan 60 mg/m² for 2 days, and CTX 50.0 mg/kg daily for 2 days. (For patients in complete remission (CR) with negative MRD before transplantation, Fludarabine and Cytarabine are administered for 3 days instead of 5 days.) Distinct from regimens at other centers, our team administers cyclophosphamide within the critical window after haploidentical stem cell infusion but before cord blood infusion, establishing a novel sequential conditioning model. This approach balances myeloablative intensity and immunomodulation, creating a favorable environment for subsequent long-term cord blood engraftment. III. Engraftment Outcomes and Clinical Value Preliminary clinical experience demonstrates that haplo-cord sequential transplantation following the FA5Cy2Bu3 conditioning regimen combined with low-dose ATG/PTCY can achieve long-term cord blood engraftment in approximately 50% of patients. By comparison, other domestic protocols (e.g., the Suzhou Protocol) rarely result in sustained cord blood engraftment. Achievement of long-term cord blood engraftment is clinically meaningful for reducing relapse rates, lowering the incidence and severity of graft-versus-host disease (GVHD), and improving patient prognosis. These outcomes represent a key advantage of the present protocol.

This study will explore the efficacy and safety of ivosidenib as maintenance therapy in patients with IDH1-mutated AML and high-risk MDS who are ineligible for transplantation, along with accompanying molecular biomarker research. Patients who meet the eligibility criteria will receive ivosidenib treatment until disease progression or unacceptable toxicity. This study will provide an effective maintenance treatment option for transplant-ineligible patients with IDH1-mutated AML and high-risk MDS.

The study is a multicentric, interventional study that evaluates the efficacy of allogeneic HLA-matched allo-HSCT consisting of myeloablative conditioning coupled with donor Treg/Tcon adoptive immunotherapy for high-risk AML patients.

This is a multicenter, prospective, single-arm clinical study designed to evaluate the efficacy and safety of the VA-CIG regimen (venetoclax combined with azacitidine, idarubicin, low-dose cytarabine and granulocyte colony-stimulating factor \[G-CSF\]) as induction therapy for previously untreated patients with fit acute myeloid leukemia (AML) who are eligible for intensive chemotherapy. This study aims to evaluate the efficacy and safety of the VA-CIG regimen in the target patient population.

Cancer treatments such as chemotherapy often affect healthy cells as well as the cancer cells and this can lead to side-effects such as low blood counts - anaemia. This can cause severe fatigue, shortness of breath and brain fog and may need regular blood transfusions. Their quality of life (QoL) is often very poor during treatment because of these side effects, and it is hard to deal with. Doctors use blood tests to decide whether a patient is well enough for treatment and when to start treatment. However, blood tests do not tell us how a person feels, and it is not the same in everyone. We need a better way for doctors to monitor patients' QoL and these symptoms so that they are physically and emotionally able to continue their treatment. It is hard for doctors to accurately assess this through speaking to their patients and doctors do not record or discuss these effects of treatment very well with patients. The aim of this study is to better understand how people feel during their treatment and how we can best use blood transfusions to maintain QoL. 80 adult patients who are starting blood cancer treatments will be asked to answer questionnaires about how they are feeling and their symptoms during their treatment. Participants will be asked to wear a smartwatch to measure their physical activity levels. Activity data collected will then be compared with their reported QoL and blood counts to help us understand when patients can tolerate difficult treatments the best and how blood transfusions affect this. Patients, their family and carers will be invited to take part in an interview to understand their views on how we can improve their care, QoL and access to transfusions. A better understanding of the impact of low blood counts on QoL can help us use blood transfusions to benefit patients' lives. This work will better match transfusions to individual peoples' needs and therefore 'personalise' blood transfusion care.

This international, multicenter, randomized (1:1), open-label phase II/III trial will evaluate the efficacy and safety of gilteritinib combined with azacitidine and venetoclax (experimental arm) versus standard "7+3" induction plus a FLT3inhibitor (quizartinib or midostaurin) (control arm) in newly diagnosed FLT3-ITD mutated AML patients eligible for intensive chemotherapy.

This study is a clinical trial designed to evaluate the safety and efficacy of a new type of CAR-T cell therapy for patients with relapsed/refractory acute myeloid leukemia (AML). The treatment involves modifying the patient's own T cells to target and eliminate leukemia cells more effectively. This is a cutting-edge therapy using anti-CLL1-CD33-NKG2D Bicephali CAR-T cells. The primary goal of this study is to determine whether this treatment can improve survival and reduce the symptoms of AML in patients whose disease has not responded to standard treatments. Participants will be closely monitored for side effects and the overall effectiveness of the treatment. Eligibility for this study includes patients who have been diagnosed with relapsed or refractory AML and have not had success with previous therapies. Participation in this study will provide access to an experimental treatment that may offer benefits beyond current treatment options, but also comes with risks. Patients, their families, and healthcare providers will be provided with full information about the procedure, potential benefits, and risks, and they will have the opportunity to ask questions before deciding whether to participate.

This study aims to evaluate whether an innovative combination therapy (CLL1 CAR-T sequential allogeneic hematopoietic stem cell transplantation) is safe, feasible and effective for the treatment of relapsed/refractory acute myeloid leukemia (R/R AML).

A study to evaluate the safety and preliminary efficacy of CLL-1-targeted CAR-T cell therapy in children aged 3 to 18 years with relapsed or refractory acute myeloid leukemia (r/r AML).

This study is a Phase II clinical trial designed to evaluate the efficacy and safety of Chidamide as maintenance therapy in high-risk acute myeloid leukemia (AML) patients following stem cell transplantation. Trial Design: The trial is a single-arm, open-label study. The experimental group plans to enroll 67 patients, while the control group (observation only) also plans to enroll approximately 67 patients, with randomization. All patients must have received induction chemotherapy prior to enrollment and may or may not have received consolidation therapy. The chemotherapy regimen was determined by the treating physician. Patients had received induction and/or consolidation therapy, achieved remission, and underwent stem cell transplantation. Study Objectives: The study aims to assess the impact of Chidamide maintenance therapy on recurrence-free survival (RFS), overall survival (OS), and the duration of complete remission. The study will also evaluate the tolerability and toxicity profile of this regimen, as well as the effect of maintenance therapy on the dynamics of minimal residual disease (MRD).

Safety and Feasibility of a Venetoclax- Augmented Treosulfan-Based Reduced Intensity Conditioning Before Allogeneic Stem Cell Transplantation in AML, MDS/AML and Higher Risk MDS

The goal of this observational study is to evaluate the changes in lipid profile parameters (total cholesterol, triglycerides, HDL-C, and LDL-C) in adult AML patients before and after intensive induction chemotherapy. The main questions it aims to answer are: * Are there correlations between metabolic changes (in lipid profile and BMI) and treatment outcomes, including remission status and incidence of chemotherapy-related complications? * Can the baseline lipid profile and BMI serve as prognostic markers for response to induction chemotherapy.? Participants will be observed before and after induction chemotherapy regarding their lipid profile, and BMI, observing any correlations between the different results with any complications, and with remission status.

This is a clincal trial initiated by investigator to evaluate the safety and efficacy of anti-CD123 CAR-NK in the treatment of patients with relapsed/refractory acute myeloid leukemia or blastic plasma cell like dendritic cell tumors.