A study to assess the efficacy and safety of ON 01910.Na given by continuous intravenous infusion for 72 hours every other week in patients with a blood disease who have failed, or are resistant to, or intolerant to Azacitidine or Decitabine treatments.

• Conditions: Myelodysplastic syndrome with excess blasts; MedDRA version: 14.0Level: HLTClassification code 10028536Term: Myelodysplastic syndromesSystem Organ Class: 10005329 - Blood and lymphatic system disorders; Therapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]

• Registration Number: EUCTR2010-019755-21-ES
• Lead Sponsor: Onconova Therapeutics Inc

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2011-11-28
• Last Update Posted: 2 October 2012

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 270

Inclusion Criteria

a. +/= 18 years of age;
b. Diagnosis of MDS confirmed within 6 weeks prior to study entry according to WHO criteria or FAB classification;
c. MDS classified as follows, according to WHO criteria and FAB classification:
- RAEB-1 (5% to 9% BM blasts)
- RAEB-2 (10% to 20% BM blasts)
- CMML (10% to 20% BM blasts) and WBC < 13,000/microL
- RAEB-t (21% to 30% BM blasts), meeting the following criteria:
- WBC < 25 x 109/L at study entry o Stable WBC at least 4 weeks prior to study entry and not requiring intervention for WBC control with hydroxyurea, chemotherapy, or leukophoresis;
d. At least one cytopenia (ANC < 1800/microL or platelet count < 100,000/microL or hemoglobin [Hgb] <10 g/dL);
e. Progression (according to 2006 IWG criteria) at any time after initiation of azacitidine or decitabine treatment during the past 2 years;or Failure to achieve complete or partial response
or
hematological improvement (according to 2006 IWG) after at least six 4-week cycles of azacitidine or four 6-week cycles of decitabine administered during the past 2 years;
or
Relapse after initial complete or partial response or hematological improvement (according to 2006 IWG criteria) observed after at least six 4-week cycles of azacitidine or four 6-week cycles of decitabine administered during the past 2 years;
or
Intolerance to azacitidine or decitabine defined by drug-related +/= Grade 3 liver or renal toxicity leading to treatment discontinuation during the past 2 years;
f. Has failed to respond to, relapsed following, not eligible, or opted not to participate in bone marrow transplantation;
g. Off all other treatments for MDS for at least 4 weeks. Filgrastim (G-CSF) and erythropoietin are allowed before and during the study as clinically indicated;
h. No medical need for induction chemotherapy;
i. Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2;
j. Willing to adhere to the prohibitions and restrictions specified in this protocol;
k. Patient (or patients legally authorized representative) must signed an informed consent document indicating that the patient understands the purpose of and procedures required for the study and is willing to participate in the study.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 135
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 135

Exclusion Criteria

Patients with any of the following will not be enrolled in the study:
a. Anemia due to factors other than MDS (including hemolysis or gastrointestinal [GI] bleeding) unless stabilized for 1 week after RBC transfusion;
b. Any active malignancy within the past year, except basal cell or squamous cell skin cancer or carcinoma in situ of the cervix or breast;
c. Uncontrolled intercurrent illness including, but not limited to, symptomatic congestive heart failure, unstable angina pectoris, or cardiac arrhythmia;
d. Active infection not adequately responding to appropriate therapy;
e. Total bilirubin +/= 1,5 mg/dL not related to hemolysis or Gilbert's disease;
f. Alanine transaminase (ALT)/aspartate transaminase (AST)+/=2.5 x upper limit of normal (ULN);
g. Serum creatinine +/=2.0 mg/dL;
h. Ascites requiring active medical management including paracentesis, or hyponatremia (defined as serum sodium value of <130 mEq/L);
i. Female patients who are pregnant or lactating;
j. Patients who are unwilling to follow strict contraception requirements (including condom use for males with sexual partners, and for females: prescription oral contraceptives [birth control pills], contraceptive injections, intrauterine device, double-barrier method [spermicidal jelly or foam with condoms or diaphragm], contraceptive patch, or surgical sterilization) before entry and throughout the study;
k. Female patients with reproductive potential who do not have a negative urine beta-human chorionic gonadotropin (HCG) pregnancy test at screening;
l. Major surgery without full recovery or major surgery within 3 weeks of ON 01910.Na treatment start;
m. Uncontrolled hypertension (defined as a systolic pressure +/=160 mmHg and/or a diastolic pressure +/=110 mmHg);
n. New onset seizures (within 3 months prior to the first dose of ON 01910.Na) or poorly controlled seizures;
o. Any other concurrent investigational agent or chemotherapy, radiotherapy, or immunotherapy;
p. Prior treatment with low-dose cytarabine during the past 2 years;
q. Investigational therapy within 4 weeks of starting ON 01910.Na;
r. Psychiatric illness or social situation that would limit the patient's ability to tolerate and/or comply with study requirements.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified