Efficacy and Safety of ON 01910.Na in Myelodysplastic Syndrome (MDS) Patients With Trisomy 8 or Classified as Intermediate-1, -2 or High Risk

• Register: ClinicalTrials.gov
• Last refreshed on: 28 January 2013
• Main ID: NCT00906334
• Date of registration: 19/05/2009
• Primary sponsor: Onconova Therapeutics, Inc.
• Public title: Efficacy and Safety of ON 01910.Na in Myelodysplastic Syndrome (MDS) Patients With Trisomy 8 or Classified as Intermediate-1, -2 or High Risk
• Scientific title: A Phase 2, Single-Arm Study To Assess The Efficacy and Safety Of 72-Hour Continuous Intravenous Dosing Of ON 01910.Na Administered Every Other Week in Myelodysplastic Syndrome Patients With Trisomy 8 or Classified as Intermediate-1, 2 or High Risk
• Date of first enrolment: May 2009
• Target sample size: 13
• Recruitment status: Completed
• URL: http://clinicaltrials.gov/show/NCT00906334
• Study type: Interventional
• Study design: Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Countries of recruitment

United States

Contacts

• Name: Peter L. Greenberg, MD
• Affiliation: Stanford University

Key inclusion & exclusion criteria

Inclusion Criteria:

- Diagnosis of MDS confirmed within 2 weeks prior to study entry according to the World
Health Organization (WHO) Criteria or the French-American-British (FAB)
Classification.

- Trisomy 8 cytogenetics (simple or combined to other karyotypes) or patient classified
as Intermediate-1 with bone marrow blasts equal to or greater than 5%, Intermediate-2
or High Risk MDS according to the IPSS score, or Patients with peripheral blood
blasts equal to or greater than 5%.

- At least one cytopenia (Absolute Neutrophil Count < 1800/µl or Platelet Count
<100,000/µl or Hemoglobin < 10 g/dL).

- Failure of, or insufficient response to Azacytidine or Decitabine administered for 4
to 6 cycles in patients classified as Intermediate-2 or High risk or to Erythrocyte
stimulating agents (failure or insufficient response defined as transfusion
dependence or Hemoglobin remaining below 10 g/dl) in Low or Intermediate-1 Risk
Trisomy 8 patients.

- 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/µl).

- ECOG Performance Status 0, 1 or 2.

- 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).

- Hypoplastic MDS (cellularity <10%).

- 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 > 2.0 mg/dL or calculated creatinine clearance < 60 ml/min/1.73 m2.

- 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; Patients who do not agree to use 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; Female patients with reproductive potential who do not have
a negative serum beta-HCG pregnancy test at screening.

- Major surgery without full recovery or major surgery within 3 weeks of ON 01910.Na
treatment start.

- Uncontrolled hypertension (defined as a systolic pressure equal to or greater than
160 mmHg and/or a diastolic pressure equal to or greater than 110 mmHg).

- 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.

- Treatment with standard MDS therapies or investigational therapy within 4 weeks of
starting ON 01910.Na.

- Psychiatric illness/social situations that would limit the patient's ability to
tolerate and/or comply with study requirements.



Age minimum: 18 Years
Age maximum: N/A
Gender: Both

Health Condition(s) or Problem(s) studied

Myelodysplastic Syndrome

Intervention(s)

Drug: ON 01910.Na

Primary Outcome(s)

Complete or partial response as defined per the 2006 International Working Group (IWG) Criteria [Time Frame: 29 weeks]

Secondary Outcome(s)

Change in International Prognostic Scoring System (IPSS) risk category [Time Frame: 29 weeks]

Hematologic Improvement according to IWG 2006 criteria [Time Frame: 29 weeks]

Time and duration of overall response [Time Frame: 29 weeks]

Secondary ID(s)

Onconova 04-17

Source(s) of Monetary Support

Please refer to primary and secondary sponsors