Study Evaluating Safety and Efficacy of JCAR017 in Subjects With Relapsed or Refractory Chronic...
LeukemiaLymphocytic4 moreThis is a Phase 1/2, open-label, multicenter study to determine the efficacy and safety of JCAR017 in adult subjects with relapsed or refractory CLL or SLL. The study will include a Phase 1 part to determine the recommended dose of JCAR017 monotherapy in subjects with relapsed or refractory CLL or SLL, followed by a Phase 2 part to further assess the efficacy and safety of JCAR017 monotherapy treatment at the recommended dose. A separate Phase 1 cohort will assess the combination of JCAR017 and concurrent ibrutinib. Another separate Phase 1 cohort will assess the combination of JCAR017 and concurrent venetoclax. In all subjects, the safety, efficacy, and pharmacokinetics (PK) of JCAR017 will be evaluated.
Ibrutinib as Early Therapy in Chronic Lymphocytic Leukemia (CLL)
Malignant Neoplasms Stated as Primary Lymphoid HaematopoieticChronic Lymphocytic Leukemia1 moreThe standard approach to managing chronic lymphocytic leukemia (CLL) and small lymphocytic leukemia (SLL) is to wait until you have symptoms before treatment is given. The goal of this clinical research study is to learn if providing earlier treatment for CLL or SLL with ibrutinib in patients who do not have symptoms will be more effective than waiting until symptoms develop. This is an investigational study. Ibrutinib is FDA approved and commercially available for the treatment of patients with CLL or SLL. It is considered investigational to give ibrutinib to CLL and SLL patients before symptoms develop. The study doctor can describe how the study drug is designed to work. Up to 50 participants will be enrolled in this study. All will take part at MD Anderson.
Total Therapy XVII for Newly Diagnosed Patients With Acute Lymphoblastic Leukemia and Lymphoma
Acute Lymphoblastic LeukemiaAcute Lymphoblastic LymphomaThe overarching objective of this study is to use novel precision medicine strategies based on inherited and acquired leukemia-specific genomic features and targeted treatment approaches to improve the cure rate and quality of life of children with acute lymphoblastic leukemia (ALL) and acute lymphoblastic lymphoma (LLy). Primary Therapeutic Objectives: To improve the event-free survival of provisional standard- or high-risk patients with genetically or immunologically targetable lesions or minimal residual disease (MRD) ≥ 5% at Day 15 or Day 22 or ≥1% at the end of Remission Induction, by the addition of molecular and immunotherapeutic approaches including tyrosine kinase inhibitors or chimeric antigen receptor (CAR) T cell / blinatumomab for refractory B-acute lymphoblastic leukemia (B-ALL) or B-lymphoblastic lymphoma (B-LLy), and the proteasome inhibitor bortezomib for those lacking targetable lesions. To improve overall treatment outcome of T acute lymphoblastic leukemia (T-ALL) and T-lymphoblastic lymphoma (T-LLy) by optimizing pegaspargase and cyclophosphamide treatment and by the addition of new agents in patients with targetable genomic abnormalities (e.g., activated tyrosine kinases or JAK/STAT mutations) or by the addition of bortezomib for those who have a poor early response to treatment but no targetable lesions, and by administering nelarabine to T-ALL and T-LLy patients with leukemia/lymphoma cells in cerebrospinal fluid at diagnosis or MRD ≥0.01% at the end of induction. To determine in a randomized study design whether the incidence and/or severity of acute vincristine-induced peripheral neuropathy can be reduced by decreasing the dosage of vincristine in patients with the high-risk CEP72 TT genotype or by shortening the duration of vincristine therapy in standard/high-risk patients with the CEP72 CC or CT genotype. Secondary Therapeutic Objectives: To estimate the event-free survival and overall survival of children with ALL and to assess the non-inferiority of TOTXVII compared to the historical control given by TOTXVI. To estimate the event-free survival and overall survival of children with LLy when ALL diagnostic and treatment approaches are used. To evaluate the efficacy of blinatumomab in B-ALL patients with end of induction MRD ≥0.01% to <1% and those (regardless of MRD level or TOTXVII risk category) with the genetic subtypes of BCR-ABL1, ABL-class fusion, JAK-STAT activating mutation, hypodiploid, iAMP21, ETV6-RUNX1-like, MEF2D, TCF3-HLF, or BCL2/MYC or with Down syndrome, by comparing event-free survival to historical control from TOTXVI. To determine the tolerability of combination therapy with ruxolitinib and Early Intensification therapy in patients with activation of JAK-STAT signaling that can be inhibited by ruxolitinib and Day 15 or Day 22 MRD ≥5%, Day 42 MRD ≥1%, or LLy patients without complete response at the End of Induction and all patients with early T cell precursor leukemia. Biological Objectives: To use data from clinical genomic sequencing of diagnosis, germline/remission and MRD samples to guide therapy, including incorporation of targeted agents and institution of genetic counseling and cancer surveillance. To evaluate and implement deoxyribonucleic acid (DNA) and ribonucleic acid (RNA) sequencing-based methods to monitor levels of MRD in bone marrow, blood, and cerebrospinal fluid. To assess clonal diversity and evolution of pre-leukemic and leukemic populations using DNA variant detection and single-cell genomic analyses in a non-clinical, research setting. To identify germline or somatic genomic variants associated with drug resistance of ALL cells to conventional and newer targeted anti-leukemic agents in a non-clinical, research setting. To compare drug sensitivity of ALL cells from diagnosis to relapse in vitro and in vivo and determine if acquired resistance to specific agents is related to specific somatic genome variants that are not detected or found in only a minor clone at initial diagnosis. Supportive Care Objectives To conduct serial neurocognitive monitoring of patients to investigate the neurocognitive trajectory, mechanisms, and risk factors. To evaluate the impact of low-magnitude high frequency mechanical stimulation on bone mineral density and markers of bone turnover. There are several Exploratory Objectives.
A Study of Cirmtuzumab and Ibrutinib in Patients With B-Cell Lymphoid Malignancies
B-cell Chronic Lymphocytic LeukemiaSmall Lymphocytic Lymphoma2 moreThis is Phase 1b/2 study to investigate the safety and effectiveness of the investigational drug, cirmtuzumab, when given in combination with ibrutinib in patients with B-cell lymphoid malignancies. Cirmtuzumab is a monoclonal antibody that attaches to a protein (called ROR 1) that is found on hematologic tumor cells. ROR1 has been shown to play a role in cell signaling that cause leukemia and lymphoma cells to grow and survive. ROR1 is rarely found on healthy cells.
Assessing the Ability of Combination Treatment With Venetoclax to Permit Time Limited Therapy in...
Chronic Lymphocytic LeukemiaSmall Lymphocytic LymphomaThis phase III trial studies how well ibrutinib and obinutuzumab with or without venetoclax work in treating patients with chronic lymphocytic leukemia. Ibrutinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Obinutuzumab is a monoclonal antibody. It binds to a protein called CD20, which is found on B cells (a type of white blood cell) and some types of cancer cells. This may help the immune system kill cancer cells. Venetoclax is in a class of medications called B-cell lymphoma-2 (BCL-2) inhibitors. It may stop the growth of cancer cells by blocking Bcl-2, a protein needed for cancer cell survival. Giving ibrutinib, obinutuzumab, and venetoclax may work better than giving ibrutinib and obinutuzumab in treating patients with chronic lymphocytic leukemia.
Blinatumomab Plus HLA-Mismatched Cellular Therapy for Relapsed/Refractory CD19+ ALL
B-Cell Acute Lymphoblastic LeukaemiaALL2 moreSingle center Phase 1 dose escalation trial of the combination of standard-of-care blinatumomab plus Haplo-Mismatched Cellular Therapy (HMCT). HMCT refers to the infusion of donor peripheral blood mononuclear cells collected via pheresis from a haploidentical family member - the procedure is analogous to giving a donor lymphocyte infusion outside of the setting of an allogeneic stem cell transplant; also known as 'microtransplantation'. The HMCT is an unselected mix of lymphocytes and leukocytes, but the product dose escalation will be done based on the T cell content. Ten recipients are planned. Each subject will be administered one infusion of HMCT during the first cycle of blinatumomab and two infusions during cycle two of blinatumomab; the CD3+ cell dose of the HMCT infusion is governed by dose escalation / de-escalation following a Bayesian method.
Ribociclib in Combination With Everolimus and Dexamethasone in Relapsed ALL
Acute Lymphoblastic Leukemia ALLThis research study is evaluating a drug called ribociclib (LEE011) given in combination with everolimus and other standard of care chemotherapy drugs as a possible treatment for relapsed or refractory ALL. The names of the drugs involved in this study are: ribociclib everolimus dexamethasone
Bendamustine/Rituximab Followed by Venetoclax and Rituximab for Treatment of Chronic Lymphocytic...
Chronic Lymphocytic LeukemiaThe purpose of this study is to determine the efficacy of bendamustine and rituximab (BR) followed by venetoclax for 12 months. The total time on therapy is 15 months. Bendamustine and rituximab is a commonly used treatment for CLL. Venetoclax is an oral drug that blocks a protein called BCL-2 which is present on CLL cells. It is approved for patients with relapsed (the cancer has come back) or refractory (the cancer did not respond) CLL who harbor a deletion in the short arm of chromosome 17 [del(17p)]. When this drug is used by itself, many patients needed to be admitted to the hospital to monitor for a complication known as tumor lysis syndrome. This is an oncologic emergency that is caused by massive destruction of tumor cells with the release of large amounts of electrolytes and other molecules into the blood that can lead to renal failure and potentially death.
Donor Stem Cell Transplantation Using α/β+ T-lymphocyte Depleted Grafts From HLA Mismatched Donors...
Acute Lymphoid Leukemia (ALL)Acute Myeloid Leukemia (AML)4 moreThis study is being done to learn whether a new method to prevent rejection between the donor immune system and the patient's body is effective.
CART22 Alone or in Combination With huCART19 for ALL
Chemotherapy Resistant Acute Lymphoblastic LeukemiaRefractory Acute Lymphoblastic LeukemiaThis is a single center, open-label, phase 1 study to determine the safety and feasibility of infusing CART22-65s with or without huCART19 after administration of lymphodepleting chemotherapy in adult patients with relapsed or refractory B-ALL.