Track topics on Twitter Track topics that are important to you
This will be a phase I/II study of 5-azacitidine in combination with vorinostat in patients with relapsed or refractory DLBCL. Combination therapy with methyltransferase inhibitors and histone deacetylase inhibitors is highly synergistic in DLBCL cells, and both classes of drugs can also synergize powerfully with standard anti-lymphoma chemotheraputics such as doxorubicin in pre-clinical studies. We hypothesize that azacytidine + vorinostat combination therapy will be safe and effective in selected patients with relapsed or refractory DLBCL. We also hypothesize that patients demonstrating objective responses to this combination therapy display specific epigenetic signatures, and that a biomarker or gene classifier can be generated which will identify those patients likely to respond.
Eligible subjects will have biopsy proven relapsed or refractory DLBCL, have preserved hematologic and other organ function, and have either progressed following or be inappropriate candidates for autologous stem cell transplantation.
Patients will be treated with 5-azacitidine via subcutaneous administration and vorinostat orally at four different dose levels as described below:
- Dose level 1: azacitidine 55 mg/m2 on days 1-5 and oral vorinostat at 300 mg BID on Days 1-7.
- Dose level 2: azacitidine 75 mg/m2 on days 1-5 and oral vorinostat at 200 mg BID on Days 1-7.
- Dose level 3: azacitidine 55 mg/m2 on days 1-5 and oral vorinostat at 300 mg BID on Days 1-14.
- Dose level 4: azacitidine 75 mg/m2 on days 1-5 and oral vorinostat at 200 mg BID on Days 1-14.
Each cycle will be of 28 days and patients will be treated for up to 6 cycles.
Up to 8 patients will be enrolled at each dose level. If at any time 2 patients in a given cohort experience DLT, enrollment to that level will be discontinued.
Efficacy will be assessed by standard radiographic and other criteria at baseline and at the end of treatment to determine ORR. Patients will be followed for 2 years or until disease progression.
Tumor samples will be obtained for correlative studies at baseline through core needle or surgical biopsy, with an additional biopsy performed on day 15 of cycle 1 as a pharmacodynamic endpoint.
Allocation: Non-Randomized, Control: Active Control, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Weill Cornell Medical College
Not yet recruiting
Weill Medical College of Cornell University
Published on BioPortfolio: 2014-07-23T21:09:07-0400
This phase II trial is studying how well vorinostat works in treating patients with relapsed or refractory indolent non-Hodgkin's lymphoma. Drugs used in chemotherapy, such as vorinostat, ...
RATIONALE: Vorinostat may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. PURPOSE: This phase II trial is studying how well vorinostat works in tre...
RATIONALE: Bortezomib and vorinostat in the laboratory may stop the growth of lymphoma cells and make them more likely to die. Giving bortezomib together with vorinostat after an autologou...
RATIONALE: Vorinostat may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Biological therapies, such as lenalidomide, may stimulate the immune syste...
This study will provide vorinostat to advanced CTCL patients who have no other treatment options for their disease. Safety and efficacy will be evaluated.
Hypoxia promotes HCC progression and therapy resistance, and there is no systemic treatment for HCC patients after sorafenib resistance. Thus, it is urgent to develop potential therapeutic regimens fo...
The C3H10T1/2 cells are considered mesenchymal stem cells (MSCs) because they can be induced to become the progenitor cells for myocytes, adipocytes, osteoblasts, and chondrocytes by the DNA methyltra...
Inoculation of hamadryas baboons with blood of leukemia ill people-induced malignant non-Hodgkin's lymphoma in experimental animals for a very considerable latency period. At close contact of inoculat...
The latest revision of lymphoma's World Health Organization classification describes the new provisional entity "Burkitt-like lymphoma with 11q aberration" (BLL, 11q) as lacking MYC rearrangement, but...
A leukemia/lymphoma found predominately in children and young adults and characterized LYMPHADENOPATHY and THYMUS GLAND involvement. It most frequently presents as a lymphoma, but a leukemic progression in the bone marrow is common.
B-cell lymphoid tumors that occur in association with AIDS. Patients often present with an advanced stage of disease and highly malignant subtypes including BURKITT LYMPHOMA; IMMUNOBLASTIC LARGE-CELL LYMPHOMA; PRIMARY EFFUSION LYMPHOMA; and DIFFUSE, LARGE B-CELL, LYMPHOMA. The tumors are often disseminated in unusual extranodal sites and chromosomal abnormalities are frequently present. It is likely that polyclonal B-cell lymphoproliferation in AIDS is a complex result of EBV infection, HIV antigenic stimulation, and T-cell-dependent HIV activation.
A form of undifferentiated malignant LYMPHOMA usually found in central Africa, but also reported in other parts of the world. It is commonly manifested as a large osteolytic lesion in the jaw or as an abdominal mass. B-cell antigens are expressed on the immature cells that make up the tumor in virtually all cases of Burkitt lymphoma. The Epstein-Barr virus (HERPESVIRUS 4, HUMAN) has been isolated from Burkitt lymphoma cases in Africa and it is implicated as the causative agent in these cases; however, most non-African cases are EBV-negative.
Two or more distinct types of malignant lymphoid tumors occurring within a single organ or tissue at the same time. It may contain different types of non-Hodgkin lymphoma cells or both Hodgkin and non-Hodgkin lymphoma cells.
A pyrimidine analogue that inhibits DNA methyltransferase, impairing DNA methylation. It is also an antimetabolite of cytidine, incorporated primarily into RNA. Azacytidine has been used as an antineoplastic agent.
In a clinical trial or interventional study, participants receive specific interventions according to the research plan or protocol created by the investigators. These interventions may be medical products, such as drugs or devices; procedures; or change...
The development and maintenance of an organism is orchestrated by a set of chemical reactions that switch parts of the genome off and on at strategic times and locations. Epigenetics is the study of these reactions and the factors that influence them. ...