Fludarabine and Total-Body Irradiation Followed By Donor Stem Cell Transplant and Cyclosporine and...
Accelerated Phase Chronic Myelogenous LeukemiaAcute Undifferentiated Leukemia181 moreThis clinical trial studies the side effects and best dose of giving fludarabine and total-body irradiation (TBI) together followed by a donor stem cell transplant and cyclosporine and mycophenolate mofetil in treating human immunodeficiency virus (HIV)-positive patients with or without cancer. Giving low doses of chemotherapy, such as fludarabine, and TBI before a donor bone marrow or peripheral blood stem cell transplant helps stop the growth of cancer or abnormal cells and helps 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). Sometimes the transplanted cells from a donor can also make an immune response against the body's normal cells. Giving cyclosporine (CSP) and mycophenolate mofetil (MMF) after the transplant may stop this from happening.
Imatinib Mesylate in Treating Patients With Advanced Cancer and Liver Dysfunction
Accelerated Phase Chronic Myelogenous LeukemiaAcute Undifferentiated Leukemia84 moreDrugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Phase I trial to study the effectiveness of imatinib mesylate in treating patients who have advanced cancer and liver dysfunction
Stem Cell Transplantation for Patients With Hematologic Malignancies
Acute Lymphoblastic LeukemiasAcute Myelocytic Leukemia6 moreChildhood leukemias which cannot be cured by chemotherapy alone may be effectively treated by allogeneic bone marrow transplantation. Moreover, for patients with chronic myelogenous leukemia (CML), allogeneic hematopoietic stem cell transplantation (HSCT) is the only proven curative modality of treatment. Patients who have received hematopoietic stem cells from an HLA matched sibling donor have proven to be less at risk for disease relapse and regimen related toxicity. However, about 70% of patients in need of HSCT do not have an HLA matched sibling donor. This necessitates the search for alternative donors, which may increase the risk of a poor outcome. The nature of the hematopoietic stem cell graft has been implicated as a primary factor determining these outcomes. The standard stem cell graft has been unmanipulated bone marrow, but recently several advantages of T-lymphocyte depleted bone marrow and mobilized peripheral blood progenitor cells (PBPC) have been demonstrated. However, T-cell depletion may increase the risk of infectious complications and leukemic recurrence while an unmanipulated stem cell graft may increase the risk of graft vs. host disease (GVHD). A key element in long range strategies in improving outcomes for patients undergoing matched unrelated donor (MUD) HSCT is to provide the optimal graft. The primary objective of this clinical trial is to estimate the incidence of acute GVHD in pediatric patients with hematologic malignancies who receive HSCT with an unmanipulated marrow graft. The results of this study can be used as the foundation for future trials related to engineering unrelated donor graft.
Stem Cell Transplantation as Immunotherapy for Hematologic Malignancies
LeukemiaAcute Lymphoblastic Leukemia7 moreBlood and marrow stem cell transplant has improved the outcome for patients with high-risk hematologic malignancies. However, most patients do not have an appropriate HLA (immune type) matched sibling donor available and/or are unable to identify an acceptable unrelated HLA matched donor through the registries in a timely manner. Another option is haploidentical transplant using a partially matched family member donor. Although haploidentical transplant has proven curative in many patients, this procedure has been hindered by significant complications, primarily regimen-related toxicity including GVHD and infection due to delayed immune reconstitution. These can, in part, be due to certain white blood cells in the graft called T cells. GVHD happens when the donor T cells recognize the body tissues of the patient (the host) are different and attack these cells. Although too many T cells increase the possibility of GVHD, too few may cause the recipient's immune system to reconstitute slowly or the graft to fail to grow, leaving the patient at high-risk for significant infection. For these reasons, a primary focus for researchers is to engineer the graft to provide a T cell dose that will reduce the risk for GVHD, yet provide a sufficient number of cells to facilitate immune reconstitution and graft integrity. Building on prior institutional trials, this study will provide patients with a haploidentical graft engineered to specific T cell target values using the CliniMACS system. A reduced intensity, preparative regimen will be used in an effort to reduce regimen-related toxicity and mortality. Two groups of patients were enrolled on this study. One group included those with high-risk hematologic malignancies and the second group included participants with refractory hematologic malignancies or undergoing a second transplant. The primary aim of the study was to estimate the relapse rate in the one group of research participants with refractory hematologic malignancies or those undergoing second allogeneic transplant. Both groups will be followed and analyzed separately in regards to the secondary objectives. This study was closed to accrual on April 2006 as it met the specific safety stopping rules regarding occurrence of severe graft vs. host disease. Although this study is no longer open to accrual, the treated participants continue to be followed as directed by the protocol.
Liposomal Daunorubicin and SU5416 in Treating Patients With Hematologic Cancer That Has Not Responded...
Chronic Myelomonocytic LeukemiaPreviously Treated Myelodysplastic Syndromes3 morePhase I/II trial to study the effectiveness of liposomal daunorubicin and SU5416 in treating patients who have hematologic cancer that has not responded to initial therapy. Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. SU5416 may stop the growth of hematologic cancer by stopping blood flow to the cancer
A Phase II Trial of SGI-110 in Patients With IPSS High and Int 2 Myelodysplastic Syndrome, Acute...
MDSTreatment of patients with WHO defined IPSS int 2 and high risk MDS , AML with 20-30% marrow blasts and CMML type 2, after failure of azacitidine or decitabine exposure for at least 6 courses, or relapse after initial response.
Phase I Clinical Study of CWP232291 in Acute Myeloid Leukemia Patients
Acute Myeloid LeukemiaChronic Myelomonocytic Leukemia2 moreCWP232291 blocks proliferation of cancer cells via activation of caspases. Active caspase have been shown to target beta-catenin, the hallmark of canonical Wnt signaling, for degradation through caspase-directed cleavage. CWP232291 targets beta-catenin for degradation and thereby inhibits the expression of cell cycle and anti-apoptotic genes such as cyclin D1 and survivin.
Donor Peripheral Blood Stem Cell Transplant and Pretargeted Radioimmunotherapy in Treating Patients...
Chronic Myelomonocytic LeukemiaMyelodysplastic/Myeloproliferative Neoplasm8 moreThis phase I trial studies pretargeted radioimmunotherapy and donor peripheral blood stem cell transplant employing fludarabine phosphate and total-body irradiation (TBI) to treat patients with high-risk acute myeloid leukemia, acute lymphoblastic leukemia, or myelodysplastic syndrome. Giving chemotherapy drugs, such as fludarabine phosphate, and TBI before a donor peripheral blood stem cell transplant helps stop the patient's immune system from rejecting the donor's stem cells. Radiolabeled monoclonal antibodies can be combined with fludarabine phosphate and TBI to find cancer cells and kill them without harming normal cells. Pretargeted radioimmunotherapy (PRIT) allows for further improved targeting of tumor cells over standard directly labeled antibodies.
Study for Epidemiology and Characterization of Myelodysplastic Syndromes (MDS) and Juvenile Myelomonocytic...
Myelodysplastic SyndromesJuvenile Myelomonocytic LeukemiaThe aim of the study is to improve the accuracy of diagnosis for children and adolescents with MDS by a standardized review of morphology and standardized cytogenetic and molecular analysis. The primary objectives of the study are: To evaluate the frequency of the different subtypes of MDS in childhood and adolescence by a standardized diagnostic approach To evaluate the frequency of cytogenetic and molecular abnormalities: Specifically using array-CGH to evaluate the frequency of subtle chromosomal imbalances, i.e. gains and losses of defined chromosomal regions, and amplifications. Specifically using mFISH to identify unknown chromosomal aberrations, particularly subtle translocations involving new candidate genes, and to better define chromosomal breakpoints. The secondary objectives of the study are: To assess survival for children and adolescents with MDS and JMML To evaluate relapse rate, morbidity and mortality in children with MDS and JMML treated by HSCT
A Study of Withdrawal of Immunosuppression and Donor Lymphocyte Infusions Following Allogeneic Transplant...
Acute LeukemiaAcute Myeloid Leukemia8 moreThere is no curative therapy once acute leukemia patients relapse after transplant. Patients who develop clinically significant graft versus host disease (GVHD) have a lower rate of relapse than those who do not develop GVHD. We are initiating this study of post-transplant fast withdrawal of immunosuppression and donor lymphocyte infusions, with a goal of achieving full donor chimerism in children with hematologic malignancies. If our hypothesis that full donor chimerism results in leukemia-free survival is correct, using immune modulation to achieve full donor chimerism should decrease relapse rate and thus increase survival. The goal of this Phase II study is to identify if achieving full donor chimerism in whole blood CD3+ and leukemia-specific (CD14/15+, CD19+, CD33+ and CD34+) subset may decrease the risk of relapse of patients undergoing allogeneic transplant for hematologic malignancy.