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

This study has been completed.
Sponsor:
Collaborator:
Onconova Therapeutics, Inc.
Information provided by (Responsible Party):
Peter L Greenberg, Stanford University
ClinicalTrials.gov Identifier:
NCT01326377
First received: March 28, 2011
Last updated: February 2, 2012
Last verified: February 2012
  Purpose

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)
Leukemia
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)
  Eligibility

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

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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01326377

Locations
United States, California
Stanford University School of Medicine
Stanford, California, United States, 94305
Sponsors and Collaborators
Peter L Greenberg
Onconova Therapeutics, Inc.
Investigators
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:
MDS
AML
Refractory Cytopenia
Refractory Anemia Dysplasia

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

ClinicalTrials.gov processed this record on September 14, 2014