ON 01910.Na for Intermediate1-2, or High Risk Trisomy 8 Myelodysplastic Syndrome (MDS)

This study has been completed.
Onconova Therapeutics, Inc.
Information provided by (Responsible Party):
Peter L Greenberg, Stanford University
ClinicalTrials.gov Identifier:
First received: March 28, 2011
Last updated: February 2, 2012
Last verified: February 2012

This is a phase 2 single arm study in which fourteen MDS patients with Trisomy 8 or classified as Intermediate-1, 2, or High risk who meet all other inclusion/exclusion criteria will receive ON 01910.Na 1800 mg/24h as an intravenous continuous infusion (IVCI) over 72 hours every other week for the first four 2-week cycles and every 4 weeks afterwards.

Condition Intervention Phase
Myelodysplastic Syndromes
Myelodysplastic Syndromes (MDS)
Acute Myeloid Leukemia (AML)
Drug: ON 01910.Na Concentrate
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 2, Single-Arm Study To Assess The Efficacy and Safety Of 72-Hour Continuous Intravenous Dosing Of ON 01910.Na Administered Once Every 2 Weeks in Myelodysplastic Syndrome Patients With Trisomy 8 or Classified as Intermediate-1, 2 or High Risk

Resource links provided by NLM:

Further study details as provided by Stanford University:

Primary Outcome Measures:
  • Response as defined per the 2000 International Working Group (IWG) Criteria in patients with MDS. [ Time Frame: 6-12 months ] [ Designated as safety issue: No ]

Enrollment: 14
Study Start Date: May 2009
Study Completion Date: February 2011
Primary Completion Date: January 2011 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: ON 01910.Na Concentrate
    ON 01910 Na 1800 mg/24h
    Other Name: Estybon
Detailed Description:

Primary Objective The primary objective of this study is to evaluate the efficacy and safety of ON 01910.Na CIV 1800 mg/24h for 72-hour infusion administered every other week for 8 weeks and every 4 weeks afterwards in achieving by week 29 a complete or partial response or hematological improvement as defined per the 2006 International Working Group (IWG) Criteria in Myelodysplastic Syndrome (MDS) patients with Trisomy 8 or classified as Intermediate-1, 2, or High risk.

Secondary Objectives

The secondary objectives are to assess:

  • Time and duration of bone marrow response
  • Complete or partial response according to International Working Group (IWG) 2006 criteria
  • Improvement of dyspoiesis as evaluated by the change in aneuploidy in bone marrow
  • Change in International Prognostic Scoring System (IPSS)
  • Responses in absolute neutrophil count, according to IWG 2006 criteria
  • Responses in platelet count, according to IWG 2006 criteria
  • Erythroid responses, according to IWG 2006 criteria
  • Time to progression
  • Overall survival at 29 and 53 weeks
  • Proportion of patients transitioning to acute myeloid leukemia (AML) at 29 and 53 weeks
  • Exploratory biomarkers on bone marrow aspirates (described in a separate companion protocol)

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

Inclusion Criteria:- > 18 years

  • Diagnosis of MDS via bone marrow aspirate and biopsy according to WHO Criteria and FAB Classification
  • Anemia requiring transfusion support with at least one unit of packed red blood cells per month for greater than or equal to 2 months or Hemoglobin < 10 g/dL OR Thrombocytopenia (platelet count < 100,000/ul) OR Neutropenia (absolute neutrophil count < 1,500/ul)
  • Failed to respond to, relapsed following, or opted not to participate in bone marrow transplantation
  • Off all other treatments for MDS (including filgrastim (G-CSF) and erythropoietin) for at least four weeks. As an exception, filgrastim (G-CSF) can be used before, during and after the protocol treatment for patients with documented febrile neutropenia (<500/ul)
  • ECOG Performance Status 0, 1 or 2
  • Adequate contraceptive [including prescription oral contraceptives (birth control pills), contraceptive injections, intrauterine device (IUD), double-barrier method (spermicidal jelly or foam with condoms or diaphragm), contraceptive patch, or surgical sterilization] before entry and throughout the study for female patients of reproductive potential
  • Female patient with reproductive potential must have a negative serum beta-HCG pregnancy test at screening
  • Willing to adhere to the prohibitions and restrictions specified in this protocol
  • Patient (or his/her legally authorized representative) must have signed an informed consent document indicating that he/she understands the purpose of and procedures required for the study and is willing to participate in the study

Exclusion Criteria:- Anemia due to factors other than MDS (including hemolysis or gastrointestinal bleeding)

  • Proliferative (WBC >= 12,000/mm^3) chronic myelomonocytic leukemia
  • Any active malignancy within the past year except basal cell or squamous cell skin cancer or carcinoma in situ of the cervix or breast
  • History of HIV-1 seropositivity
  • Uncontrolled intercurrent illness including, but not limited to symptomatic congestive heart failure, unstable angina pectoris or cardiac arrhythmia
  • Active infection not adequately responding to appropriate therapy.
  • Total bilirubin > 1.5 mg/dL not related to hemolysis or Gilbert's disease, ALT or AST > 2 X ULN
  • Serum creatinine > 1.5 mg/dL or calculated creatinine clearance < 60 ml/min/1.73 m^2
  • Ascites requiring active medical management including paracentesis, or hyponatremia (defined as serum sodium value of <134 Meq/L).
  • Women patients who are pregnant or lactating
  • Male patients with female sexual partners who are unwilling to follow the strict contraception requirements described in this protocol
  • Major surgery without full recovery or major surgery within 3 weeks of ON 01910.Na treatment start.
  • Uncontrolled hypertension (defined as a systolic pressure >= 160 and/or a diastolic pressure >= 110)
  • New onset seizures (within 3 months prior to the first dose of ON 01910.Na) or poorly controlled seizures
  • Any concurrent investigational agent or chemotherapy, radiotherapy or immunotherapy
  • Psychiatric illness/social situations that would limit the patient's ability to tolerate and/or comply with study requirements
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01326377

United States, California
Stanford University School of Medicine
Stanford, California, United States, 94305
Sponsors and Collaborators
Peter L Greenberg
Onconova Therapeutics, Inc.
Principal Investigator: Peter L Greenberg Stanford University
  More Information

No publications provided

Responsible Party: Peter L Greenberg, Professor Emeritus, Stanford University
ClinicalTrials.gov Identifier: NCT01326377     History of Changes
Other Study ID Numbers: HEMMDS0020, 04-17, 16214
Study First Received: March 28, 2011
Last Updated: February 2, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by Stanford University:
Refractory Cytopenia
Refractory Anemia Dysplasia

Additional relevant MeSH terms:
Leukemia, Myeloid, Acute
Leukemia, Myeloid
Myelodysplastic Syndromes
Neoplasms by Histologic Type
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Chromosome Aberrations
Pathologic Processes
Chromosome Duplication

ClinicalTrials.gov processed this record on April 17, 2014