
Study of TCP-ATRA for Adult Patients With AML and MDS
Acute Myelogenous LeukemiaMyelodysplastic Syndromes1 moreAcute Myeloid Leukemia (AML) is a diverse disease that is fatal in the majority of patients. Acute promyelocytic leukemia (APL) however, a subtype of AML accounting for 5% of all cases, is very curable. APL cells are highly sensitive to the retinoid all-trans-retinoic acid (ATRA), which effectively differentiates the leukemic clone. Over 80% of APL patients can be cured with ATRA based therapies. For patients with non-APL AML, ATRA has little effect. Consequently, 85% of these patients will succumb to their disease despite conventional approaches. Little is known about mechanisms of resistance to ATRA in non-APL AML. This knowledge gap limits the use of ATRA in a disease that already has few effective therapies. The investigators' preliminary data suggest that non-APL AML cells can be re-sensitized to ATRA when combined with lysine-specific demethylase 1 (LSD 1) inhibitors. The investigators' publication in Nature Medicine showed that LSD1 inhibition with tranylcypromine (TCP), unlocked the ATRA-driven therapeutic response in non-APL AML. Notably, treatment with ATRA and TCP markedly diminished the engraftment of primary human AML cells in murine models, indicating that the combination may target leukemia-initiating cells (LIC). The investigators' data identify LSD1 as a therapeutic target and strongly suggest that it may contribute to ATRA resistance in non-APL AML. The investigators' central hypothesis is that ATRA combined with TCP will be safe and effective in a clinical population, and that this approach will suppress LICs and restore myeloid differentiation programs in patients with non-APL AML. Testing this hypothesis with the phase I clinical trial outlined in this protocol, will establish a new treatment paradigm in AML and extend the important anti-cancer effects of ATRA to all AML subtypes.

An Open Label Phase II Pharmacokinetic and Pharmacodynamic Assessment of the Potential for QTc Prolongation...
Acute Myeloid Leukemia (AML)Acute Lymphoblastic Leukemia (ALL)1 moreThe purpose of this study is to assess the effects of CPX-351 on cardiac repolarization, assess plasma drug levels, asses serum copper levels, and assess drug levels in urine. Efficacy and Safety will be assessed in all patients enrolled to the study.

Selinexor With Fludarabine and Cytarabine for Treatment of Refractory or Relapsed Leukemia or Myelodysplastic...
Acute Myeloid Leukemia (AML)Acute Lymphoblastic Leukemia (ALL)2 moreThe purpose of this study is to test the safety of selinexor (KPT-330) and to find the highest dose of selinexor (KPT-330) that can be given safely when it is combined with two chemotherapy drugs (fludarabine and cytarabine). This study will be done in two parts: Phase I and Phase II. The goal of Phase I is to find the highest tolerable dose of selinexor (KPT-330) that we can give to patients with leukemia or MDS, when it is combined with fludarabine and cytarabine. The goal of the subsequent Phase II portion of the study (insert NCT ID of SELHEM-2) is to give the highest dose of selinexor (KPT-330) in combination with fludarabine/cytarabine that was found in Phase I to be safe for children with leukemia or MDS. The investigators will examine the effect of this combination treatment. PRIMARY OBJECTIVE: Determine a tolerable combination of selinexor, fludarabine, and cytarabine in pediatric patients with relapsed or refractory hematologic malignancies included acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), mixed phenotype acute leukemia (MPAL) and myelodysplastic syndrome (MDS). SECONDARY OBJECTIVES: To characterize the pharmacokinetics of selinexor, when administered in tablet form, after the first dose and at steady-state, as well as in combination with fludarabine and cytarabine To estimate the overall response rate of selinexor given with fludarabine and cytarabine in patients with relapsed or refractory hematologic malignancies

Lenalidomide and Ibrutinib in Treating Patients With Relapsed or Refractory Chronic Lymphocytic...
Recurrent B-Cell Prolymphocytic LeukemiaRecurrent Chronic Lymphocytic Leukemia4 moreThis phase I trial studies the side effects and best dose of lenalidomide when given together with ibrutinib in treating patients with chronic lymphocytic leukemia or small lymphocytic lymphoma that has returned after a period of improvement (relapsed) or does not respond to treatment (refractory). Biological therapies, such as lenalidomide, may stimulate the immune system in different ways and stop cancer cells from growing. Ibrutinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving lenalidomide together with ibrutinib may work better in treating chronic lymphocytic leukemia or small lymphocytic lymphoma.

A Phase I Study of 5-Azacytidine in Combination With Chemotherapy for Children With Relapsed or...
Lymphoblastic LeukemiaAcute4 moreThis is a Phase I study with a conditional cohort expansion phase to evaluate the feasibility of, and to obtain preliminary efficacy data about, pretreatment with Azacytidine (AZA) for 5 days followed by fludarabine/cytarabine chemotherapy regimen in pediatric acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) patients who are refractory to primary treatment or who relapsed.

An Expanded Access, Open-Label Study of Obinutuzumab (GA101) Plus Chlorambucil in Patients With...
Chronic Lymphocytic LeukemiaThis is a multicenter, open-label, single-arm, expanded access treatment study designed to provide obinutuzumab to patients with previously untreated Chronic Lymphocytic Leukemia (CLL) in combination with chlorambucil and to evaluate the safety and efficacy of obinutuzumab administered in combination with chlorambucil. This study will enroll patients with previously untreated CD20-positive CLL requiring treatment according to the IWCLL guidelines (Hallek et al 2008), as assessed by the investigator.

Preventing Stem Cell Transplant Complications With a Blood Separator Machine
MDS (Myelodysplastic Syndrome)Myeloproliferative Disorder4 moreBackground: - Researchers are working to make stem cell transplant procedures safer and more effective. One complication of transplants is graft-versus-host disease (GVHD). This complication happens when certain white blood cells from the donor attack the recipient's own body. Researchers want to test a blood separator machine that may help remove more of the donor's white blood cells before transplant. They will study donors and recipients during stem cell transplant to see how well this process can prevent GVHD and other complications. Objectives: - To see if a new blood separator machine can improve outcomes of stem cell transplants. Eligibility: Individuals between 10 and 75 years of age who are having a stem cell transplant for leukemia or other blood-related cancers. Donors for the stem cell transplant. Design: Recipients and donors will be screened with a physical exam and medical history. Donors will have two blood collection procedures. The first will collect only white blood cells, and return the rest of the blood. After the first collection, participants will have filgrastim injections to help their stem cells enter their blood. Then, they will have a second blood collection for the stem cells. Recipients will have radiation and chemotherapy to prepare for the stem cell transplant. They will then have the stem cell transplant with the donor cells that have been treated with the blood separator machine. Recipients will be monitored closely after the procedure. They may receive some of their donor's white blood cells if needed to fight serious infections. Recipients will have the regular standard of care after their transplant. Blood samples will be taken and any side effects will be monitored and treated.

Safety Study of CPX-351 in Children With Relapsed Leukemia or Lymphoma
Acute Myeloid LeukemiaAcute Lymphoblastic Leukemia6 moreThe purpose of this study is to test the safety of a study drug called CPX-351. This drug has been tested in adults but not yet in children and adolescents. This study tests different doses of the drug to see which dose is safer in children and adolescents. Patients who have blood cancer are being asked to take part in this study . Blood cancers may include leukemia and lymphoma. Patients able to be in this study have already been treated with standard chemotherapy for their disease and the disease is still growing or has come back. CPX-351 is a drug that is not yet approved by the United States Food and Drug Administration (FDA) and is only used in research studies like this one. CPX-351 is made up of two chemotherapy drugs that patients may have already received called cytarabine and daunorubicin that are now packaged together. Another purpose of this study is to collect blood samples for special research studies. Researchers want to study how much of the CPX-351 is in the body over time. These studies are call pharmacokinetic studies or PK studies for short. PK studies require the collection of several blood samples before and after participants are given the study drug.

Pneumococcal Vaccine in Untreated CLL Patients
Chronic Lymphocytic LeukemiaThe purpose of the study is to determine whether patients with chronic lymphocytic leukaemia (CLL) will benefit from vaccination with a 13-valent conjugated pneumococcal vaccine, Prevenar13, compared with a conventional 23-valent capsular polysaccharide vaccine in terms of immune response.

A Phase II Study of Selinexor Plus Cytarabine and Idarubicin in Patients With Relapsed/Refractory...
Acute Myeloid Leukemia (Relapsed/Refractory)Acute Myeloid Leukemia (AML) is currently treated with chemotherapy by combining several drugs with different ways of inhibiting the cell growth. In this trial, standard chemotherapeutics that have proven their effectiveness for years, Ara-C and Idarubicin, will be combined with a new drug called Selinexor. Selinexor inhibits the growth of cancer cells by keeping certain proteins in the nucleus which control the cell growth.