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

Leukemia Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01326377
• Other study ID #: HEMMDS0020
• Secondary ID: 04-1716214
• Status: Completed
• Phase: Phase 2
• First received: March 28, 2011
• Last updated: February 2, 2012
• Start date: May 2009
• Est. completion date: February 2011

Study information

• Verified date: February 2012
• Source: Stanford University
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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.

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)

Recruitment information / eligibility

• Status: Completed
• Enrollment: 14
• Est. completion date: February 2011
• Est. primary completion date: January 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Acute Myeloid Leukemia (AML)
• Leukemia
• Leukemia, Myeloid, Acute
• Myelodysplastic Syndromes
• Myelodysplastic Syndromes (MDS)
• Preleukemia
• Syndrome

Intervention

Drug:
• ON 01910.Na Concentrate
ON 01910 Na 1800 mg/24h

Locations

Country	Name	City	State
United States	Stanford University School of Medicine	Stanford	California

Sponsors (2)

Lead Sponsor	Collaborator
Peter L Greenberg	Onconova Therapeutics, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Response as defined per the 2000 International Working Group (IWG) Criteria in patients with MDS.		6-12 months	No