
Dasatinib and Low Intensity Chemotherapy for Ph+ Acute Lymphoblastic Leukemia
LeukemiaLymphoblastic1 moreThe use of imatinib in combination or in association with chemotherapy is now considered as the gold standard for the treatment of Ph+ ALL. The complete remission (CR) rate is 90% versus 20% to 40% with chemotherapy alone. The combination of imatinib, vincristine and dexamethasone is a well tolerated regimen in aged patients and is also associated with a high CR rate of 80% to 90% in patient aged 55 years and over. However, despite high CR rates, the progression free survival rate at 12 months of patients treated with the combination of imatinib and chemotherapy is 30% to 50%. Relapses remain frequent and only patients intensified with allogenic haematopoietic stem cell transplantation are in long term remission. This strategy is not fully applicable to most patients aged 55 years and over. Relapses after or during imatinib therapy in patients with Ph+ ALL are associated with BCR-ABL tyrosine kinase domain mutation in 80% of cases, predominantly of the p-loop. The exact incidence of the T315I mutation is controversial and can be estimated to be near 50%. Conversely, the detection of the T315I or F317 mutation in a patient is a very strong predictor of relapse. Dasatinib is a potent SCR and BCR-ABL tyrosine kinase inhibitor with preserved in vitro activity in most of the BCR-ABL mutated cell lines, except for the T315I and F317 mutations. This is also the case in vivo, with patients harbouring BCR-ABL TK domain mutations remaining sensitive to dasatinib. The CHR rate in Ph+ ALL resistant to imatinib is 33% and the median progression-free survival is 3.7 months. Progression free survival (PFS) rate at 12 months is 22%. The goal of this trial is to evaluate the efficacy and the tolerance of the combination of dasatinib with chemotherapy in the front-line setting as induction and consolidation therapy in Ph+ ALL patient aged 55 years and over. A European consensus has been reached to adopt a common chemotherapeutic schedule for patients aged 55 years and over. This schedule will be used in this trial with the addition of dasatinib as concomitant therapy during induction and alternating with chemotherapy during consolidation and maintenance. A CR rate of 90% and a progression free survival of 60% at 12 months are expected. The patients will be prospectively monitored for minimal residual disease and mutation.

Safety Study of BTK Inhibitor, DTRMWXHS-12, Used Singly or in Combination, in CLL and B-cell Lymphomas...
Chronic Lymphocytic LeukemiaB-Cell LymphomaThis study will evaluate the safety, antitumor activity and preliminary pharmacokinetics of an investigational drug product, DTRMWXHS-12, in patients with chronic lymphocytic leukemia or other B-cell lymphomas. DTRMWXHS-12 will be evaluated as a single agent, and in combination. This study will be conducted in two parts: phase Ia and Ib. Both parts will explore escalating doses of DTRMWXHS-12. The phase Ia study will evaluate DTRMWXHS-12 monotherapy. The phase Ib study will evaluate DTRMWXHS-12 combinations.

Blinatumomab in Combination With AMG 404 for the Treatment of Adults With Relapsed or Refractory...
Acute Lymphoblastic LeukemiaThe primary objective of this phase 1b study is to evaluate the safety and tolerability of blinatumomab and AMG 404 in combination in adults with R/R B-ALL and to estimate the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) of AMG 404 when combined with continuous intravenous infusion (cIV) blinatumomab.

TC-110 T Cells in Adults With Relapsed or Refractory Non-Hodgkin Lymphoma or Acute Lymphoblastic...
Non Hodgkin LymphomaAcute Lymphoblastic Leukemia4 moreTC-110 T cells are a novel cell therapy that consists of autologous genetically engineered T cells expressing a single-domain antibody that recognizes human CD19, fused to the CD3-epsilon subunit which, upon expression, is incorporated into the endogenous T cell receptor (TCR) complex. This is a Phase 1/2 open-label study to evaluate the safety of autologous genetically engineered TC-110 T cells in patients with aggressive NHL (DLBCL, PMBCL, TFL), high-risk indolent NHL (including MCL), or adult ALL.

Muscle Dysfunction in Patients With Hematological Diseases Referred to Stem Cell Transplant
Hematologic DiseasesChronic Myeloid Leukemia6 morePURPOSE: To investigate the effect of the disease and HSCT on muscle dysfunction and to investigate the prognostic role of muscle dysfunction at critical decision points in patients with hematological diseases referred to hematopoietic stem cell transplant (HSCT). HSCT: Patients diagnosed with malignant hematological diseases who are referred to myeloablative HSCT, to a myeloablative "reduced toxicity conditioning" regime with Fludarabine and Treosulfane (FluTreo) or to non-myeloablative HSCT.

A Roll-over Study to Provide Continued Treatment With Lyophilized Pegaspargase (S95014) in Pediatric...
Acute Lymphoblastic LeukemiaThe purpose of this study is to provide treatment with lyophilized S95014 in pediatric patients with ALL who completed the CL2-95014-002 study during the induction phase and who are clinically benefitting from S95014 without major toxicity.

Inotuzumab Ozogamicin and Chemotherapy in Treating Patients With Recurrent or Refractory B-cell...
Recurrent B Acute Lymphoblastic LeukemiaRecurrent B Lymphoblastic Lymphoma2 moreThis phase I trial studies the best dose of inotuzumab ozogamicin in combination with chemotherapy in treating patients with B-cell acute lymphoblastic leukemia that has come back (recurrent) or that does not respond to treatment (refractory). Inotuzumab ozogamicin is a monoclonal antibody, called inotuzumab, linked to a toxic agent called ozogamicin. Inotuzumab attaches to CD22 positive cancer cells in a targeted way and delivers ozogamicin to kill them. Drugs used in chemotherapy, such as etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin, 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 inotuzumab ozogamicin in combination with chemotherapy may kill more cancer cells than with chemotherapy alone in treating patients with recurrent or refractory B-cell acute lymphoblastic leukemia.

Outcomes in Pediatric and Young Adult B-Cell Malignancies After Commercially Available Immunotherapy...
Lymphoid LeukemiaTo use a consistent and standardized platform to retrospectively and prospectively study children and young adults with B cell malignancies receiving Immunotherapy, blinatumomab and/or inotuzumab ozogamicin.

Sequential Regimen of Bendamustin-Debulking Followed by Ofatumumab and Ibrutinib in CLL Patients...
Chronic Lymphocytic LeukemiaA prospective, open-label, multicentre phase-II trial to evaluate the efficacy and safety of a sequential regimen of bendamustine followed by ofatumumab and ibrutinib followed by ibrutinib and ofatumumab maintenance in CLL patients.

Phase I/II Study of Bosutinib in Combination With Inotuzumab Ozogamicin in CD22-positive PC Positive...
B Acute Lymphoblastic Leukemia With t(9;22)(q34.1;q11.2); BCR-ABL1Blast Phase Chronic Myelogenous Leukemia9 moreThis phase I/II trial studies the side effects and best dose of bosutinib when given together with inotuzumab ozogamicin and to see how well it works in treating patients with acute lymphoblastic leukemia or chronic myeloid leukemia that has come back or does not respond to treatment. Bosutinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Immunotoxins, such as inotuzumab ozogamicin, are antibodies linked to a toxic substance and may help find cancer cells that express CD22 and kill them without harming normal cells. Giving bosutinib together with inotuzumab ozogamicin may be a better treatment for acute lymphoblastic leukemia or chronic myeloid leukemia.