Belimumab in Patients With Chronic Lymphocytic Leukemia
Chronic Lymphoid Leukemia in RelapseThis study is a phase II trial of belimumab in combination with rituximab/venetoclax in patients with refractory or relapsed chronic lymphocytic leukemia (CLL). Treatment of CLL has drastically changed in the past years as new therapeutic agents have gained clinical approval. The combination rituximab/venetoclax over a course of two years is approved as second line therapy especially in patients with high risk CLL (del17p), showing high remission rates and achievement of MRD (minimal residual disease) negativity. The next goals in CLL therapy are now to increase the rate of MRD negativity and to achieve an earlier MRD negativity during the course of treatment to allow for a reduction of treatment time and therefore treatment-induced toxicities. In line with other hematologic diseases, progression free survival depends on remission status, especially MRD negativity, after last treatment as MRD positivity after therapy indicates the persistence of treatment resistant CLL cells. One mechanism of therapy resistance has been described as reduced sensitivity to rituximab-induced antibody dependent cell-mediated cytotoxicity (ADCC) by natural killer (NK) cell production of B-lymphocyte stimulator (BlyS, also called BAFF), which can be bound by belimumab, a human anti-BAFF antibody. Moreover, recombinant human (rh)BAFF can dose dependently reverse cytotoxic effects of venetoclax, which could also be restored by the application of belimumab. This led to the conceptualization of this clinical trial, in which belimumab is applied as a weekly subcutaneous injection in combination with standardrituximab/venetoclax treatment for up to 24 months in relapsed and refractory CLL patients. By removing BAFF from the CLL microenvironment we aim to increase the efficacy of rituximab/venetoclax treatment to achieve higher and earlier MRD negativity rates and allow for an abbreviated treatment.
CPX-351 and Glasdegib for Newly Diagnosed Acute Myelogenous Leukemia With MDS Related Changes or...
Acute Myelogenous Leukemia (AML) Due to TherapyAcute Myeloid Leukemia With Myelodysplasia-Related ChangesThis is a phase 2 single-arm, open-label clinical trial determining efficacy of CPX-351 in combination with Glasdegib in subjects with Acute Myelogenous Leukemia with myelodysplastic syndrome related changes or therapy-related acute myeloid leukemia.
A Study of Gilteritinib (ASP2215) Combined With Chemotherapy in Children, Adolescents and Young...
Acute Myeloid Leukemia (AML)Acute Myeloid Leukemia With FMS-like Tyrosine Kinase 3 (FLT3) Mutation / Internal Tandem Duplication (ITD)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 1 or 2 treatment cycles in phase 1 or 2 will have the option to participate in long term treatment (LTT) with gilteritinib (for up to 2 years).
Donor Stem Cell Transplant With Treosulfan, Fludarabine, and Total-Body Irradiation for the Treatment...
Acute LeukemiaAcute Lymphoblastic Leukemia18 moreThis phase II trial studies how well a donor stem cell transplant, treosulfan, fludarabine, and total-body irradiation work in treating patients with blood cancers (hematological malignancies). Giving chemotherapy and total-body irradiation before a donor stem cell transplant helps stop the growth of cells in the bone marrow, including normal blood-forming cells (stem cells) and cancer cells. It may also stop the patient's immune system from rejecting the donor's stem cells. When the healthy stem cells from a donor are infused into the patient, they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. The donated stem cells may also replace the patient's immune cells and help destroy any remaining cancer cells.
The Study for CML Who Failed Prior TKIs or With T315I Mutation or Ph+ ALL Who Failed Prior TKIs...
Chronic Myeloid LeukemiaAcute Lymphoblastic LeukemiaThis protocol will allow ponatinib with refractory Chronic Myeloid Leukemia or Ph+ Acute Lymphoblastic Leukemia
Galinpepimut-S Versus Investigator's Choice of Best Available Therapy for Maintenance in AML CR2/CRp2...
Acute Myeloid LeukemiaTo assess the safety and efficacy of galinpepimut-S (GPS) compared with investigator's choice of best available therapy (BAT) on overall survival (OS) in subjects with acute myeloid leukemia (AML) who are in second or later complete remission (CR2) or second or later complete remission with incomplete platelet recovery (CRp2).
Trial Testing Safety of IL-21 NK Cells for Induction of R/R AML
Allogeneic Stem Cell Transplant RecipientBlasts 10 Percent or More of Bone Marrow Nucleated Cells2 moreThis phase I trial studies the side effects of donor natural killer (NK) cell therapy in treating patients with acute myeloid leukemia that has come back (recurrent) or has not responded to treatment (refractory). Natural killer cells are a type of immune cell. Immunotherapy with genetically modified NK cells from donors may induce changes in the body's immune system and may interfere with the ability of cancer cells to grow and spread.
CAR-T CD19 for Acute Myelogenous Leukemia With t 8:21 and CD19 Expression
Acute Myeloid LeukemiaChimeric antigen receptor (CAR-T) engineered T cells against the CD19 protein have been shown to be effective against acute lymphoma and lymphocytic leukemia and are approved by the US (FDA), European (EMA) and Health Basel. However, little information exists on using CD19CAR for treatment of recurrent or irresponsible to previous treatment acute myeloid leukemia. The proposed study will include patients with recurrent disease or those with disease irresponsible to common treatments and they will be treated with CAR-T CD19.
Study of HQP1351 in Subjects With Refractory CML and Ph+ ALL
LeukemiaMyeloid5 moreA multi-center, open-label, randomized, phase Ib study to evaluate the pharmacokinetics (PK) of HQP1351 and to determine the recommended phase 2 dose (RP2D) of HQP1351 in subjects with CML chronic phase (CP), accelerated phase (AP), or blast phase (BP) or with Ph+ ALL, who have experienced resistance or intolerance to at least two tyrosine kinase inhibitors (TKIs) or in subjects with Ph+ B-cell precursor (BCP) ALL or lymphoid blast phase CML (CML LBP), who have experienced resistance or intolerance to at least one second or later generation TKI.
CD19+Targeted CAR-T Cell Therapy for Relapsed/Refractory CD19+ B Cell Leukemia and Lymphoma
LeukemiaLymphoma10 moreThis is a single arm study to evaluate the efficacy and safety of CD19-targeted CAR-T cells therapy for patients with relapsed/refractory CD19+ B Cell Leukemia and Lymphoma.