Randomized Study of ON 01910.Na in Refractory Myelodysplastic Syndrome Patients With Excess Blasts
Summary
The primary objective of this study is to compare overall survival (OS) in patients receiving ON 01910.Na + best supportive care (BSC) to OS of patients receiving BSC in a population of patients with myelodysplastic syndrome (MDS) with excess blasts (5% to 30% bone marrow blasts) who have failed azacitidine or decitabine treatment. This patient population has no available therapy and a short life expectancy (approximately 4 months). The high level of bone marrow activity of ON 01910.Na documented in Phase 1 and 2 studies has the potential to delay substantially the transition of MDS to Acute Myeloid Leukemia(AML), a very significant and severe complication, which shortens survival of these MDS patients.
Description
This is a Phase III open-label, randomized, controlled, multicenter study (up to 50 centers). Approximately 270 patients with MDS classified as RAEB-1 and RAEB-2 using the WHO classification and as RAEB-t and chronic myelomonocytic leukemia (CMML) using the FAB classification who failed, became intolerant to, or progressed after treatment with 5-azacitidine or decitabine administered during the past 2 years, will be randomized in a 2:1 ratio into the following 2 treatment regimens:
- Best Supportive Care (BSC) + ON 01910.Na 1800 mg/24 hr administered as a 72-hr continuous intravenous (CIV) infusion on Days 1, 2, and 3 of a 2-week cycle (N = approximately 180 patients)
- BSC (N = approximately 90 patients).
Patients will be stratified at entry by bone marrow (BM) blasts (5% to 19% vs. 20% to 30%). After completing the first eight 2-week cycles (i.e., after 16 weeks of treatment), the frequency of further 72-hr CIV infusions will be decreased to an administration on Days 1, 2, and 3 of a 4-week cycle.
Patients will remain treated on study until 2006 International Working Group (IWG) progression criteria are met (i.e., 50% increase of BM blasts or worsening of cytopenias) or until death from any cause, whichever comes first.
Patients who progress to Acute Myeloid Leukemia (AML) while on study should be offered either standard treatment for AML or enrollment in an appropriate investigational study if they are eligible. These treatments with their start and end dates should be documented and patient survival time will be documented for all randomized patients.
Cross-over of BSC patients to ON 01910.Na after progression will not be allowed. However, patients in the BSC-only group will be allowed, as medically justified, access to low-dose cytarabine 20 mg/m2 subcutaneously (SC) once daily for the first consecutive 14 days of each 28-day cycle, up to 4 cycles, until progression or unacceptable toxicity develops. Low-dose cytarabine will be delayed as needed until recovery of blood counts. All study participants will be allowed, as medically justified, access to RBC and platelet transfusions and to growth factors (erythropoietin, Filgrastim [G-CSF]). Hydroxyurea will be allowed to manage blastic crisis with hyperleukocytosis when patients transition to leukemia.
Study Design
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Conditions
Myelodysplastic Syndromes
Intervention
ON 01910.Na
Location
Virginia G. Piper Cancer Center
Scottsdale
Arizona
United States
85258
Status
Recruiting
Source
Onconova Therapeutics, Inc.
Results (where available)
Links
- Source: http://clinicaltrials.gov/show/NCT01241500
- Information obtained from ClinicalTrials.gov on May 15, 2013
Medical and Biotech [MESH] Definitions
Myelodysplastic-myeloproliferative Diseases
Clonal myeloid disorders that possess both dysplastic and proliferative features but are not properly classified as either MYELODYSPLASTIC SYNDROMES or MYELOPROLIFERATIVE DISORDERS.
Hematopoietic Cell Growth Factors
These growth factors comprise a family of hematopoietic regulators with biological specificities defined by their ability to support proliferation and differentiation of blood cells of different lineages. ERYTHROPOIETIN and the COLONY-STIMULATING FACTORS belong to this family. Some of these factors have been studied and used in the treatment of chemotherapy-induced neutropenia, myelodysplastic syndromes, and bone marrow failure syndromes.
Myelodysplastic Syndromes
Clonal hematopoietic stem cell disorders characterized by dysplasia in one or more hematopoietic cell lineages. They predominantly affect patients over 60, are considered preleukemic conditions, and have high probability of transformation into ACUTE MYELOID LEUKEMIA.
Hematologic Neoplasms
Neoplasms located in the blood and blood-forming tissue (the bone marrow and lymphatic tissue). The commonest forms are the various types of LEUKEMIA, of LYMPHOMA, and of the progressive, life-threatening forms of the MYELODYSPLASTIC SYNDROMES.
Aortic Arch Syndromes
Conditions resulting from abnormalities in the arteries branching from the ASCENDING AORTA, the curved portion of the aorta. These syndromes are results of occlusion or abnormal blood flow to the head-neck or arm region leading to neurological defects and weakness in an arm. These syndromes are associated with vascular malformations; ATHEROSCLEROSIS; TRAUMA; and blood clots.
Clinical Trials
Phase I Study of ON 01910.Na in Refractory Leukemia or Myelodysplastic Syndrome (MDS)
This is an open-label, Phase I study to determine the highest amount of the study drug, ON 01910.Na, that can be safety given to patients with high risk myelodysplastic syndromes (MDS) or...
For MDS patients who have not responded to or have progressed after an initial response to DNA methyltransferase inhibitors (DNMTI) and are not stem cell transplant candidates, therapeutic...
Safety and Pharmacokinetic Study of Oral ON 01910.Na in Patients With Myelodysplastic Syndrome
In other clinical studies, ON 01910.Na has been safely given intravenously to Patients with advanced cancers. However, to treat some Patients, it may be better if ON 01910.Na could be give...
This study will explore the efficacy and safety of a regimen of ON 01910.Na as a 48-hour continuous intravenous infusion once a week for 3 weeks of a 4-week cycle in MDS patients with Tris...
Study of 48-Hour Infusion of ON 01910.Na in Patients With MDS or AML
The primary objective of this study is to evaluate the efficacy and safety of ON 01910.Na Concentrate when it is administered as an intravenous continuous infusion (IVCI) over 48 hours onc...
PubMed Articles
How to manage lower-risk myelodysplastic syndromes.
Patients with lower-risk myelodysplastic syndromes (MDSs), usually defined as having an International Prognostic Scoring System score of 1.0 or less, and/or
Clonal architecture of secondary acute myeloid leukemia.
The myelodysplastic syndromes are a group of hematologic disorders that often evolve into secondary acute myeloid leukemia (AML). The genetic changes that underlie progression from the myelodysplastic...
The genetic basis of phenotypic heterogeneity in myelodysplastic syndromes.
Myelodysplastic syndromes (MDS) are malignant clonal disorders of haematopoietic stem cells and their microenvironment, affecting older individuals (median age ∼70 years). Unique features that are a...
Cyclin D proteins are elevated in many cancer cells, and targeted deletion of cyclin D1 gene in the mammary tissues protects mice from breast cancer. Accordingly, there is an increasing awareness of t...
ABSTRACT As with most genetic cancer predisposition syndromes, inherited susceptibility to myelodysplastic syndrome (MDS) and acute leukemia (AL) is likely to be more common than previously appreciate...
