Personalized Kinase Inhibitor Therapy Combined With Chemotherapy in Treating Patients With Newly...
Acute Lymphoblastic LeukemiaAcute Myeloid LeukemiaThis phase IB trial studies the feasibility of using a functional laboratory based study to determine how well the test can be used to select personalized kinase inhibitor therapy in combination with standard chemotherapy in treating patients with newly diagnosed acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL). It also evaluates safety and potential efficacy. Kinase inhibitor is a type of substance that blocks an enzyme called a kinase. Human cells have many different kinase enzymes, and they help control important cell functions. Certain kinases are more active in some types of cancer cells and blocking them may help keep the cancer cells from growing. Testing samples of blood from patients with AML and ALL in the laboratory with kinase inhibitors may help determine which kinase inhibitor has more activity against cancer cells and which one should be combined with standard of care chemotherapy. Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving a personalized kinase inhibitor therapy combined with standard chemotherapy may be a better treatment for AML and ALL.
Pilot Study of Redirected Autologous T Cells Engineered to Contain Humanized Anti-CD19 in Patients...
Acute Lymphocytic LeukemiaDiffuse Large Cell LymphomaThis is a pilot study to evaluate humanized CD19 redirected autologous T cells (or huCART19 cells) in patients with relapsed or refractory CD19+ leukemia and lymphoma that was previously treated with cell therapy. This study is targeting pediatric patients aged 1-24 years with CD19+ B cell malignancies with no available curative treatment options (such as autologous or allogeneic stem cell transplantation) who have a limited prognosis with currently available therapies and were previously treated with a B cell directed engineered cell therapy product.
Phase I Study of MLN 9708 in Addition to Chemotherapy for the Treatment of Acute Lymphoblastic Leukemia...
Acute Lymphoblastic LeukemiaLymphoblastic Lymphoma2 moreThis research study is evaluating a combination of drugs considered standard treatment for children and young adults with acute lymphoblastic leukemia (ALL), in combination with a new drug called MLN 9708. Additionally, the study is also evaluating if bone marrow or stem cell transplantation, which will be given to some participants, helps to prevent ALL from returning.
Phase I Study of Adoptive Immunotherapy With Enriched and Expanded Autologous Natural Killer (NK)...
Acute Lymphoblastic LeukemiaComplete Hematologic Remission (CHR)1 moreThe present study aims at studying how safe and tolerable a new therapy for patients with Acute Lymphoblastic Leukemia (ALL) is. This new therapy consists of an immunotherapy, that is an approach focusing on the immune system, and it targets ALL patients in complete remission but who may still have the disease at a cellular level (this is called 'minimal residual disease'). For any further information, please, discuss with your treating physician.
Phase I/II Trial of Early Infusion of Rapidly-generated Multivirus Specific T Cells (MVST) to Prevent...
Chronic Lymphocytic LeukemiaCML (Chronic Myelogenous Leukemia)3 moreAllogeneic hematopoetic stem cell transplantation (SCT) is frequently complicated by life threatening viral reactivation. Conventional antiviral therapy is suboptimal for cytomegalovirus (CMV), adenovirus (AdV) and Epstein-Barr virus (EBV) and nonexistent for BK virus (BKV). An alternative approach to prevent viral reactivation is to infuse virus-specific cytotoxic T cells (CTL) prepared from the donor early after SCT. Such multivirus-specific CTL cells (MVST) have been successfully used in a number of centers to prevent or treat CMV, Ad and EBV. Activity of BKV-reactive cells has not been studied. Multi virus-specific T cells (MVST) are donor lymphocytes that are highly enriched for viral antigens and expanded in vitro before infusion into the transplant recipient. Viral reactivation is a particular problem inT cell depleted SCT. Median time to CMV reactivation is estimated as 28 days post T-depleted transplant, but infusion of MVST within the immediate post-SCT period has not been previously studied. This protocol will be the first of a planned series of cellular therapies to be layered on our existing T lymphocyte depleted transplant platform protocol 13-H-0144. The aim of this study is to determine the safety and efficacy of very early infusion of MVST directed against the four most common viruses causing complications after T-depleted SCT. GMP-grade allogeneic MVST from the stem cell donor will be generated using monocyte-derived donor dendritic cells (DCs) pulsed with overlapping peptide libraries of immunodominant antigens from CMV, EBV, Ad, and BKV and expanded in IL-7 and IL-15 followed by IL-2 for 10-14 days. A fraction of the routine donor leukapheresis for lymphocytes obtained prior to stem cell mobilization will be used to generate the MVST cells. MVST passing release criteria will be cryopreserved ready for infusion post SCT. Eligible subjects on NHLBI protocol 13-H-0144 will receive a single early infusion of MVST within 30 days (target day +14, range 0-30 days) post SCT. Phase I safety monitoring will continue for 6 weeks. Viral reactivation (CMV, EBV, Ad, BK) will be monitored by PCR by serial blood sampling. The only antiviral prophylaxis given will be acyclovir to prevent herpes simplex and varicella zoster reactivation. Subjects with rising PCR exceeding threshold for treatment, or those with clinically overt viral disease will receive conventional antiviral treatment. Patients developing acute GVHD will receive standard treatment with systemic steroids. These patients are eligible for reinfusion of MVST when steroids are tapered. The clinical trial is designed as a single institution, open label, non-randomized Phase I/II trial of MVST in transplant recipients, designed as 3-cohort dose escalation Phase I followed by a 20 subject extension Phase II at the maximum tolerated dose of cells. Safety will be monitored continuously for a period of 6 weeks post T cell transfer. The primary safety endpoint will be the occurrence of dose limiting toxicity, defined as the occurrence of Grade IV GVHD or any other SAE that is deemed to be at least probably or definitely related to the investigational product. The primary efficacy endpoint for the phase II will be the proportion of CMV reactivation requiring treatment at day 100 post transplant. Secondary endpoints are technical feasibility of MSVT manufacture, patterns of virus reactivation by PCR, and clinical disease from EBV, Ad, BK, day 100 non-relapse mortality.
Pevonedistat With VXLD Chemotherapy for Adolescent/Young Adults With Relapsed/Refractory ALL or...
Refractory Acute Lymphoblastic LeukemiaRelapsed Acute Lymphoblastic LeukemiaThe investigators postulate that Pevonedistat will be effective in patients with relapsed/refractory acute lymphoblastic leukemia (ALL) when combined with a standard backbone ALL chemotherapy regimen.
Safety of Expanded Haploidentical Natural Killer Cells for Leukemia
LeukemiaAcute Myeloid2 moreThe purpose of this study is to estimate the safety of ex vivo expanded haploidentical natural killer (NK) cells for patients with leukemia.
Palbociclib and Dexamethasone in Treating Participants With Relapsed or Refractory B-Cell Acute...
Recurrent B Acute Lymphoblastic LeukemiaRefractory B Acute Lymphoblastic LeukemiaThis phase I trial studies the side effects and best dose of palbociclib when given together with dexamethasone in treating participants with B-cell acute lymphoblastic leukemia that has come back after a period of improvement or does not respond to treatment. Palbociclib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Dexamethasone is a steroid medication that is used in combination with other medications to treat B-cell acute lymphoblastic leukemia. Giving palbociclib together with dexamethasone may work better in treating patients with B-cell acute lymphoblastic leukemia.
CCCG Relapsed Acute Lymphoblastic Leukemia 2017 Study in Children
Acute Lymphoblastic Leukemiain RelapseRelapsed acute lymphoblastic leukaemia (ALL) has a poorer outcome than newly diagnosed ALL patients with only about 40% overall survival after re-treatment. The study CCCG Relapsed ALL 2017 study will adopt the UK R3 study stratification and treatment backbone with two new agents added. There will be a 4-week induction, followed by two consolidation courses. High-risk patients will receive allogeneic stem cell transplant. While intermediate and standard risk groups will continue maintenance treatment for another 2 years or one year. New agents will be added aiming at improving survival outcome. Study of adding anti-CD20 antibody (rituximab) with chemotherapy: CD20 is found to be expressed in 40-50% of B-lineage ALL, and rituximab has been studied in adult ALL with superior survival (75% vs 47%,). There is little experience of using rituximab in pediatric ALL thus a CCCG Relapsed ALL 2017 Study will perform the study assessing the remission rate and MRD response of CD20+ ALL treated with rituximab. Six doses of rituximab and will be monitored the week 5 MRD and relapse rate as study outcome. (This arm was terminated in October 2020 after interim analysis showing lack of efficacy) Adding bortezomid during the induction: The very early or early bone marrow relapse has low remission rate. Previous case studies showed that Bortezomib, a proteasome inhibitor, may achieve remission in refractory ALL, 80% remission in B-ALL with combination of chemotherapy and bortezomib. Thus adding bortezomib, may improve the remission rate, thus bridging to allogeneic stem cell transplant. Adding bortezomib in the relapsed chemotherapy protocol may increase the toxicity and even treatment related mortality. In this protocol, we suggested to add during the induction therapy.
MRD/Risk-oriented Therapy of Adult Ph- ALL Including Pegylated Asparaginase and Lineage-targeted...
Untreated Philadelphia Positive Acute Lymphoblastic LeukemiaDe Novo2 moreThis study will be conducted in different centres and will study adult patients with Philadelphia chromosome-negative (Ph-) acute lymphoblastic leukemia (ALL). The study treatment will include a induction/consolidation therapy incorporating pegylated Asparaginase (Peg-ASP) and lineage-targeted high-dose methotrexate plus other antileukemic drugs, for the achievement of an early negative minimal residual disease (MRD) status. The MRD study supports a risk/MRD-oriented final consolidation phase.