Active clinical trials for "Leukemia"

To evaluate if hyper-fractionated TBI or TMLI followed by Treg/Tcon adoptive immunotherapy improve cGvHD/disease free survival after allogeneic HSCT in patients affected by high-risk acute leukemias or other hematologic malignancy where HSCT is indicated.

Nilotinib vs imatinib in patients with newly diagnosed CML-CP

Long-term follow-up studies have demonstrated significant late toxicities of total body irradiation (TBI), which are most marked in children radiated at a young age. Growth failure, decline in cognitive function, and endocrine abnormalities have all been described. Good outcomes can be achieved with alkylating agents only as a preparative regimen. This plan will use a combination of busulfan and cyclophosphamide (Bu/Cy) with or without antithymocyte globulin (ATG) to reduce the late toxicities of therapy that includes TBI.

Decitabine can up-regulate a series of immune associated proteins, including cancer testis antigens (CTA), major histocompatibility complex (MHC), co-stimulatory molecules and adhesion molecules, which suggests a potential benefit for a following adoptive T cell therapy. In addition, decitabine induce FOXP3 expression in CD4+ T cells and convert CD4+ T cells into T regulatory cells(Tregs). As a result, Graft versus host disease(GVHD) can be reduced by treatment of decitabine.

The cure rate for childhood acute lymphoblastic leukemia (ALL) has increased significantly in recent decades and expected cure rates now exceed 85%. In recent years, Tyrosine Kinase Inhibitor(TKI) has improved outcome of Philadelphia chromosome positive (Ph+)ALL . But in some high risk groups, The prognosis of patients is still very bad and the relapse rate is high. Clearly, new therapies are urgently needed to prevent and /or treat relapsed ALL.

Acute leukemias are a heterogeneous group of hematologic malignancies. They result from clonal expansion of immature cells whose number is greater than 20% in bone marrow. Childhood acute leukemias are the most common pediatric malignancies. In Europe and the United states, they represent about 35% of childhood cancers. 80% of them are acute lymphoblastic leukemia (ALL) and 15-20% of acute myeloid leukemia (AML). Current treatments allow a cure in about 80% of ALL, while this level is only 50% in AML.Acute leukemia diagnosis is based on the multidisciplinary exploration of leukemia cells by different techniques: Cellular: cytology, immunophenotyping and cytochemistry Cytogenetic: conventional (karyotype) and molecular (FISH) cytogenetic Molecular: RT-PCR and RQ-PCR Cytogenetic studies are performed at time of acute leukemia diagnosis. Indeed, the WHO 2008 classification of acute leukemia is based largely on the presence of recurrent cytogenetic and molecular abnormalities. The most frequent chromosomal aberrations have been associated with specific clinical and biological characteristics and are now used as diagnosis and prognostic markers. These chromosomal abnormalities affect genes involving in the leukemogenesis process. These rearrangements are of several types: Fusion genes causing : Repression of transcriptional activity of genes involved in differentiation of hematopoietic cells (AML1-ETO, PML-RARA…) Deregulation of signal transduction pathway (eg BCR-ABL chimeric protein with constitutive tyrosine kinase activity) Changing in the state of chromatin condensation resulting changes of transcription (MLL gene rearrangements in 11q23, MOZ en 8p11…) Deregulation of genes expression: chromosomal rearrangements can sometimes induce deregulation of adjacent genes to the breakpoint. For example, inv(3)(q21q26) or t(3;3)(q21;q26) induce over expression of transcriptional factor EVI-1. Loss of function due to deletion of variable size in genomic regions containing genes with a role in the differentiation, apoptosis, or cell proliferation (eg IKZF1, PAX5…) In addition to the karyotype, which allows to have a global view of the genome; FISH, a targeted technique, is used to highlight invisible abnormalities on karyotype (cryptic abnormalities) or the time of karyotype failure. However, conventional and molecular cytogenetic techniques do not highlight any abnormalities (eg different partners involved in the formation of fusion genes in particular for MLL gene rearrangement, mutations) hence our interest in next generation sequencing.Indeed, the high throughput targeted sequencing messenger RNAs (RNA-seq) has the avantage of allow identification of different types of mutations in a single test, with exception of epigenetic mutations. The importance of RNAs sequencing rather than DNA genomic is the one hand, a very significant decrease in the volume of sequences to analyze because transcribed mRNA genes represent about 5% of the genome size and secondly, a better identification of chimeric genes. The RNA-seq has used as a research tool in hematologic malignancies. The purpose of this project is to use innovative technology to develop a new diagnostic and prognostic new tool in hematological malignancies. 50 acute leukemias will be tested and results will be analyzed according to three criteria: Quantity, quality and relevance of information provided for the diagnosis, monitoring and therapeutic management compared to a conventional strategy Period required to obtain results and methods to decrease the analysis time so that results can be integrated into therapeutic decisions. Economic evaluation, which will calculate the cost of this diagnosis option and assess the cost/benefit ratio In future, other innovative approaches will be implemented (study of imbalances genomic abnormalities by array-CGH, transcriptome analysis with micro-array, and study of methylome) to identify the "molecular signature" of each leukemia and set of informative abnormalities for diagnosis, prognosis and treatment of disease and monitoring of residual disease.

The goal: to evaluate the role of high dose ara-c plus idarubicin and mitoxantrone consolidation followed by maintenance in the setting of high total cumulative anthracyclines dose(720-660 mg/m2).

This study will compare the clinical outcomes of transplants from family-mismatched/haploidentical donors (FMT) with transplants from 8/8-matched unrelated donor (MUT), which is a current gold standard donors when lacking of HLA-matched-siblings Primary objectives: Overall survival of FMT may be similar to that of MUT Secondary objectives: i. Comparison of disease-free survival, relapse, non-relapse mortality, immune reconstitution cytomegalovirus infection, and acute or chronic graft-versus-host disease between FMT and MUT. ii. Investigation of possible biomarkers related with above events after transplantation

The purpose of this study is to evaluate the interest of maintenance treatment with interleukin-2 by randomizing the patients being not allogeneic transplanted in complete remission after induction and consolidation chemotherapy concerning the event free survival.

The MAC-HAPLO-MUD trial is a randomized prospective phase III trial comparing HLA 10/10 matched unrelated donor and haploidentical allogeneic hematopoietic stem cell transplantation after myeloablative conditioning regimen in patients, age 15 years or older, with Acute Myeloid Leukemia (AML) or Acute Lymphoblastic Leukemia (ALL) or Myeloproliferative Syndrome (SMP) or Myelodysplastic Syndromes (SMD) and requiring allogeneic hematopoietic stem cell transplantation. Primary endpoint is the 1-year progression free survival without acute grade II-IV GvHD and without moderate and severe chronic GvHD.