A Study of Oral AMN107 in Adults With Chronic Myelogenous Leukemia (CML) or Other Hematologic Malignancies...
Chronic Myelogenous LeukemiaAcute Lymphoblastic Leukemia (Philadelphia Chromosome Positive)2 moreThe purpose of this trial is to assess the efficacy, safety, tolerability, biologic activity, and pharmacokinetics of AMN107 in six groups of patients with one of the following conditions: Relapsed/refractory Ph+ Acute lymphoblastic leukemia (ALL) (arm 1) Group A - Imatinib failure only (arms 2, 3 and 4) imatinib-resistant or intolerant CML - Chronic Phase (CP) imatinib-resistant or intolerant CML - Accelerated Phase (AP) imatinib-resistant or intolerant CML - Blast Crisis (BC) Group B - Imatinib and other TKI failure (arms 2, 3 and 4) imatinib-resistant or intolerant CML - Chronic Phase (CP) imatinib-resistant or intolerant CML - Accelerated Phase (AP) imatinib-resistant or intolerant CML - Blast Crisis (BC) Hypereosinophilic syndrome/chronic eosinophilic leukemia (HES/CEL) (arm 5) Systemic mastocytosis (Sm) (arm 6)
Non-myeloablative Allogeneic Transplantation for the Treatment of Multiple Myeloma
Blood CancerMultiple MyelomaMixed chimerism transplantation is an approach to allogeneic transplants that attempts to decrease regimen-related toxicity by using non-myeloablative preparatory regimens; establish mixed chimerism using low dose total body irradiation along with immunosuppression using cyclosporine and mycophenolate mofetil; suppress graft-vs-host and host-vs-graft reactions to allow a mixed chimeric state to be established, encourage tolerance and prevent graft-vs-host disease (GvHD) during the mixed chimerism period and use donor lymphocyte infusions to convert the patient to a full chimera while developing a graft-vs-tumor effect.
Study of ABT-751 in Patients With Refractory Hematologic Malignancies
Hematological MalignanciesABT-751 is a new antitumor drug that that interferes with cell division. The goal of this clinical research study is to find the highest safe dose of ABT-751 that can be given as a treatment for refractory hematologic malignancies. The safety and side effects of ABT-751 will also be studied.
Fludarabine Phosphate, Low-Dose Total Body Irradiation, and Donor Stem Cell Transplant in Treating...
Accelerated Phase Chronic Myelogenous LeukemiaAdult Acute Lymphoblastic Leukemia in Remission43 moreThis clinical trial studies fludarabine phosphate, low-dose total body irradiation, and donor stem cell transplant in treating patients with hematologic malignancies or kidney cancer. Giving chemotherapy drugs, such as fludarabine phosphate, and total-body irradiation before a donor peripheral blood stem cell transplant helps stop the growth of cancer cells. It may also stop the patient's immune system from rejecting the donor's stem cells. The donated stem cells may replace the patient's immune cells and help destroy any remaining cancer cells (graft-versus-tumor effect). Giving an infusion of the donor's T cells (donor lymphocyte infusion) after the transplant may help increase this effect. Sometimes the transplanted cells from a donor can also make an immune response against the body's normal cells. Giving cyclosporine before the transplant and cyclosporine and mycophenolate mofetil after the transplant may stop this from happening.
A Safety Evaluation of Drotrecogin Alfa (Activated) in Patients With Blood Cancer, Severe Infection...
SepsisHematologic Neoplasms2 moreThe purpose is to determine how Drotrecogin Alfa (activated) will affect patients with blood cancers who develop severe sepsis within 60 days of starting chemotherapy in preparation for bone marrow transplant (BMT).
Modified Stem Cell Transplant Procedure to Treat Patients With Blood and Immune System Cancers
Hematologic NeoplasmsThis study will investigate the safety and effectiveness of a modified stem cell transplant procedure for treating cancers of the blood and immune system. Patients with cancers and pre-cancerous conditions originating in blood or immune system cells can sometimes benefit greatly from, and even be cured by, transplants of stem cells (cells produced by the bone marrow that mature into blood cells). In addition to producing new bone marrow and restoring normal blood production and immunity, the donated cells fight any residual tumor cells that might have remained in the body, in what is called a graft-versus-tumor effect. However, severe problems, and sometimes death, may follow these transplants as a result of the high-dose chemotherapy and radiation that accompany the procedure. Also, donated immune system cells called T cells sometimes attack healthy tissues in a reaction called graft-versus-host-disease (GVHD), damaging organs such as the liver, intestines and skin. This study will use the following strategies to try to reduce these risks: induction chemotherapy to reduce patient's immunity in an attempt to prevent rejection of the donated stem cells; reduced-intensity conditioning chemotherapy that is easier for the body to tolerate and involves a shorter period of complete immune suppression; donation of immune cells called T helper type 2 (Th2) cells instead of T cells to try to reduce the risk of serious GVHD; treatment with methotrexate and cyclosporine to try to reduce the risk of serious GVHD. Patients between 12 and 75 years of age with non-Hodgkin's lymphoma, Hodgkin's lymphoma, multiple myeloma, chronic lymphocytic leukemia, chronic myelogenous leukemia, acute myelogenous leukemia, acute lymphocytic leukemia, myelodysplasia, idiopathic myelofibrosis, polycythemia vera, or chronic myelomonocytic leukemia may be eligible for this study. Candidates will have a medical history, physical and dental examinations, blood and urine tests (including a blood test for genetic match with the donor), lung and heart function tests, and X-ray studies. A bone marrow biopsy may be done to evaluate disease status. Patients with lymphoma may have a nuclear medicine test called a positron emission tomography (PET) scan. Participants will have a central venous line (large plastic tube) placed into a major vein. This tube can stay in the body and be used during the entire treatment period to deliver the donated stem cells and give medications, including chemotherapy and other drugs, antibiotics and blood transfusions, and to withdraw blood samples. Treatment will start with induction chemotherapy, which will include the drugs fludarabine, cyclophosphamide, etoposide, doxorubicin, vincristine, and prednisone. Some patients may also receive an antibody called rituximab. Patients will receive one to three cycles of this treatment, depending on their response to the drugs. (One cycle consists of 5 days on drug therapy followed by a 16-day rest period.) Several days before the transplant procedure, patients will start conditioning chemotherapy with cyclophosphamide and fludarabine. Three days after the conditioning therapy is completed, the stem cells will be infused. To help prevent GVHD, patients will take four doses of methotrexate (by vein) shortly after the transplant, and cyclosporine (by mouth or by vein) for about 6 months after the transplant. The average hospital stay for stem cell transplantation is 3 to 4 weeks. After discharge, patients will return for frequent follow-up visits for 3 months. Monthly visits will be scheduled for the next 3 months, then every 3 months for the next 18 months, and less frequently for a total of at least 5 years post-transplant. These visits will include bone marrow aspirates and biopsies, blood draws, and other tests to monitor disease status.
A Phase 1, Dose Finding Study of CC-90002 in Subjects With Advanced Solid and Hematologic Cancers...
Hematologic NeoplasmsCC-90002-ST -001 is an open-label, Phase 1, dose escalation clinical study in subjects with advanced, refractory solid and hematologic cancers.
Studyof Allogeneic Hematopoietic Stem Cell Transplantation From One Haplotype Mismatch Related Donor...
Hematologic NeoplasmsAllogeneic (Allo) hematopoietic stem cell transplantation (HSCT) is a recognized curative procedure for hematological malignancies. It is now well known that this property is related to the graft-versus-tumor (GVT) effect developed from the immunocompetent cells contained in or generating from the donor graft. For years, however, and despite this unique antitumoral activity, Allo-HSCT has been restricted to a limited number of patients due to two major limitations: the toxicity of the procedure and the absence of a donor for every single patients. More recently the stage has dramatically changed with respect to these two restraints. Over the last decade, many studies have established the feasibility of Allo-HSCT in older patients but the availability of MRD is even less frequent in elderlies, likely related to medical contraindication for graft donation or sibling deaths. UD are routinely used but associated with a high incidence of GVHD. As compared to younger populations, unrelated cord-blood HSCT is seldom performed in this population and numbers decrease with age due to the feared risk of supposed increased lethal infectious complications related to the effect of the delayed immune reconstitution in elderlies. Thus the need for alternative donors allowing for a safe and efficient transplantation is still unmet. In consequence, overall, despite the fact that Allo-HSCT feasibility has been established in the oldest patients, all these lacks contribute eventually to maintain a low rate of allo-HSCT performed in a population with the higher incidence of hematologic malignancies that usually present with the poorest prognosis. Thus it is critical developing innovative efficient therapeutic strategies answering this unmet-medical need. In this perspective, Haplo-HSCT could represent a part of the answer in this aged population. It offers the potential advantage to offer a rapid donor determination for virtually every single patient. In addition, our data suggest that in elderlies haplo-HSCT using T-repleted graft, RIC and PT-HDCy presents low NRM and retains an antitumor effect despite low GVHD incidences. They also suggest that haplo-HSCT may conduct to better outcome than URD-HSCT as an alternative to MRD-HSCT. It may also be associated with lower costs (no graft purchase and low post-transplant complications rate) and better QOL likely related to low cGVHD-rate. In addition the conduct of such trial at a time when the diffusion of the strategy in this population is just starting is really crucial before widespread uncontrolled dissemination. The investigators propose to address this question by prospectively comparing these 2 strategies in elderly patients without MRD, in terms of efficacy, safety and including the prospective evaluation study of quality-of-life (QOL). They will conduct a national, multicenter, open-label, comparative, randomized phase III trial in patients with hematological malignancies justifying an allo-HSCT from an alternative donor when a MRD has not been identified. When MRD search is recognized to be a failure, patients will be included in the clinical trial after informed consent and randomized in the two strategies based on donor search: Reference group: Unrelated Donor group Investigational group: Haplo Donor Group Investigators will use a composite end-point embracing the three main causes of failure: death, relapse and severe cGVHD (as a surrogate endpoint for QOL). We will analyze the HSCT usual objectives as GHVD, NRM, relapse and survival. A specific study of patients' health related quality of life will also be conducted using the FACT-BMT questionnaire. In addition, the success of the two strategies in term of transplant completion (donor determination, transplant realization and time to do so) will be compared.
Nonmyeloablative Hematopoietic Cell Transplantation (HCT) for Patients With Hematologic Malignancies...
LeukemiaMDS2 moreThe purpose of this study is to determine whether stem cells collected from a donor's blood stream will be as safe and effective as using bone marrow collected from a donor's pelvic bone.
Study of Orally Administered AG-881 in Patients With Advanced Hematologic Malignancies With an IDH1...
Acute Myeloid Leukemia (AML)Myelodysplastic Syndrome1 moreThe purpose of this Phase I, multicenter study is to evaluate the safety, pharmacokinetics, pharmacodynamics and clinical activity of AG-881 in advanced hematologic malignancies that harbor an IDH1 and/or IDH2 mutation