Study of Cordycepin Plus Pentostatin in Patients With Refractory TdT-Positive Leukemia
Summary
This is a two-part, open-label, Phase I/II study in subjects with relapsed or refractory TdT-positive leukemia for which no standard therapies are expected to result in durable remission.
Description
In the first phase the Study Objectives are to:
- Define the maximally tolerated dose (MTD) and recommended dose (RD) for administration of cordycepin as a 1-hour IV infusion, administered 1 hour following administration of an IV bolus of pentostatin, in subjects with refractory TdT-positive leukemia;
- Determine plasma ADA levels prior to pentostatin infusion and at 60 and 120 minutes after administration of pentostatin;
- Determine the single and multiple dose pharmacokinetics (PK) of cordycepin given 1 hour after a fixed dose of pentostatin;
- Assess cordycepin pharmacodynamics by measurement of blast cell apoptosis from peripheral blood smears;
- Measure and quantitate any clinical responses in refractory TdT-positive leukemia patients following cordycepin/pentostatin administration.
In the second phase, the Study Objectives are to assess the safety, PK, and clinical outcomes of cordycepin in combination with pentostatin, at the RD, in a 20 subject cohort
Study Design
Control: Dose Comparison, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Conditions
Refractory TdT-Positive Leukemia
Intervention
Cordycepin plus Pentostatin
Location
Dana Farber Cancer Institute
Boston
Massachusetts
United States
02115
Status
Recruiting
Source
OncoVista, Inc.
Results (where available)
Links
- Source: http://clinicaltrials.gov/show/NCT00709215
- Information obtained from ClinicalTrials.gov on July 15, 2010
Medical and Biotech [MESH] Definitions
Pentostatin
A potent inhibitor of ADENOSINE DEAMINASE. The drug induces APOPTOSIS of LYMPHOCYTES, and is used in the treatment of many lymphoproliferative malignancies, particularly HAIRY CELL LEUKEMIA. It is also synergistic with some other antineoplastic agents and has immunosuppressive activity.
Leukemia, Myeloid, Accelerated Phase
The phase of chronic myeloid leukemia following the chronic phase (LEUKEMIA, MYELOID, CHRONIC-PHASE), where there are increased systemic symptoms, worsening cytopenias, and refractory LEUKOCYTOSIS.
Anemia, Refractory, With Excess Of Blasts
Chronic refractory anemia with granulocytopenia, and/or thrombocytopenia. Myeloblasts and progranulocytes constitute 5 to 40 percent of the nucleated marrow cells.
Leukemia, Myelogenous, Chronic, Bcr-abl Positive
Clonal hematopoetic disorder caused by an acquired genetic defect in PLURIPOTENT STEM CELLS. It starts in MYELOID CELLS of the bone marrow, invades the blood and then other organs. The condition progresses from a stable, more indolent, chronic phase (LEUKEMIA, MYELOID, CHRONIC PHASE) lasting up to 7 years, to an advanced phase composed of an accelerated phase (LEUKEMIA, MYELOID, ACCELERATED PHASE) and BLAST CRISIS.
Philadelphia Chromosome
An aberrant form of human CHROMOSOME 22 characterized by translocation of the distal end of chromosome 9 from 9q34, to the long arm of chromosome 22 at 22q11. It is present in the bone marrow cells of 80 to 90 per cent of patients with chronic myelocytic leukemia (LEUKEMIA, MYELOGENOUS, CHRONIC, BCR-ABL POSITIVE).
Clinical Trials
RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells. PURPOSE: Ph...
RATIONALE: Drugs used in chemotherapy, such as pentostatin, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Monocl...
Pentostatin for High Risk and Refractory Chronic Graft Versus Host Disease in Children
This is a multicenter trial through the Pediatric Blood and Marrow Transplant Consortium. The Primary hypothesis of this study is that because of its effect as a potent immunosuppressive...
This study aims to assess the rate of complete and overall response using rituximab and pentostatin with and without cyclophosphamide, to monitor and assess toxicity of this regimen, and t...
Pentostatin in Treating Patients With Refractory Chronic Graft-Versus-Host Disease
RATIONALE: Pentostatin may be effective in treating chronic graft-versus-host disease by stopping the immune system from rejecting donor stem cells or donor white blood cells. PURPOSE: Th...
PubMed Articles
BACKGROUND AND OBJECTIVE: Pentostatin is an irreversible inhibitor of adenosine deaminase and has been used to prevent graft-versus-host disease (GVHD) and to treat both acute and chronic GVHD. Dose r...
Cordycepin, a nucleoside isolated from Cordyceps sinensis, is an inhibitor of polyadenylation and has an antitumor effect. We used CGTH W-2, a follicular thyroid carcinoma cell line, to study the mech...
Cordycepin (3'-deoxyadenosine) is the main functional component of Cordycepins militaris, a renowned traditional Chinese medicine, which has been shown to possess anti-tumor, anti-inflammatory, anti-d...
The in Vivo and in Vitro Stimulatory Effects of Cordycepin on Mouse Leydig Cell Steroidogenesis.
Cordycepin, a pure compound of Cordyceps sinensis (CS), is known as an adenosine analog. We have found that CS stimulated Leydig cell steroidogenesis. Here we investigated the in vivo and in vitro eff...
