A study which compares Rigosertib with standard of care treatment inpatients with ineffective production of blood cells (myelodysplasticsyndrome) who have undergone treatment with azacitidine or decitabinewithout success
- Conditions
- Myelodysplastic SyndromeTherapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2015-001476-22-HU
- Lead Sponsor
- Onconova Therapeutics, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 225
a. 18-81 years of age;
b. Disease classification and cytogenetics confirmed within 8 weeks prior
to or during screening as follows:
• RAEB-1 per World Health Organization (WHO) MDS criteria (5% to
<10% BM blasts)
• RAEB-2 per WHO MDS criteria (10% to <20% BM blasts)
• RAEB-t per modified French-American-British (FAB) classification
(20% to 30% BM blasts)
c. At least one cytopenia (ANC < 1800/µL or platelet count <
100,000/µL or hemoglobin [Hgb] < 10 g/dL)
d. Progression (according to 2006 IWG criteria) at any time after
initiation of AZA or DAC treatment or
Failure to achieve complete or partial response or hematological
improvement (HI) (according to 2006 IWG) after at least six 4-week
cycles of AZA or either four 4-week or four 6-week cycles of DAC
administered or
Relapse after initial complete or partial response or HI (according to
2006 IWG criteria) or
Intolerance to AZA or DAC
e. Total duration of prior HMA therapy = 9 months and/or total = 9
cycles of prior HMA therapy in = 12 months
f. Last dose of AZA or DAC within 6 months before the planned date of
randomization; however, must be off these treatments for = 4 weeks
before randomization
g. Has failed to respond to, relapsed following, not eligible for, or opted
not to participate in allogeneic stem cell transplantation
h. Off all treatments for MDS (including AZA and DAC) for = 4 weeks
before randomization; growth factors (G-CSF, erythropoietin and TPO)
and transfusions are allowed before and during the study as clinically
indicated
i. Patients with 5q- syndrome should have failed to respond to or
progressed on treatment with lenalidomide where available and
indicated
j. Eastern Cooperative Oncology Group (ECOG) performance status of 0,
1 or 2
k. Willing to adhere to the prohibitions and restrictions specified in this
protocol
l. Patient must sign an Informed Consent form indicating that the patient
understands the purpose of and procedures required for the study and is
willing to participate in the study. In case a patient is incapable of giving
consent, the patient;'s legally authorized representative (appointed
earlier by the court) must give consent. However, should the patient in
any manner indicate the will not to participate this takes precedence and
must be respected.
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 113
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 112
a. Previous participation in a clinical study of IV or oral rigosertib;
patients who failed screening for other rigosertib studies may be
screened for participation in this study
b. Eligible to receive induction chemotherapy, such as 7-10 days of
cytosine arabinoside and 2-3 days of an anthracycline, or high-dose
cytarabine (HDAC)
c. Patient previously diagnosed with AML (defined as a bone marrow or
peripheral blood blast percentage >30%)
d. Suitable candidate to receive allogeneic stem cell transplantation;
patient is eligible for study if a suitable candidate refuses to undergo an
allogeneic stem cell transplant or a suitable donor cannot be found
e. Any active malignancy within the past year, except basal cell or
squamous cell skin cancer or carcinoma in situ of the cervix or breast
f. Uncontrolled intercurrent illness including, but not limited to,
symptomatic congestive heart failure or unstable angina pectoris
g. Active infection not adequately responding to appropriate therapy
h. Total bilirubin =1.5 mg/dL not related to hemolysis or Gilbert's
disease
i. Alanine transaminase (ALT)/aspartate transaminase (AST) =2.5 x
upper limit of normal (ULN)
j. Serum creatinine =2.0 mg/dL or calculated eGFR (estimated
Glomerular Filtration Rate) <60 mL/min
k. Known active HIV, hepatitis B or hepatitis C, where active is defined
as follows: a. HIV or Hepatitis C – presence of viral load b. Hepatitis B –
antigen positive
l. Uncorrected hyponatremia (defined as serum sodium value of <130
mEq/L)
m. Female patients of child-bearing potential (pre-menopausal and not
surgically sterilized) who are breast-feeding or have a positive blood
beta-human chorionic gonadotropin (ß-HCG) pregnancy test at
Screening
n. Female patients of child-bearing potential and male patients with
sexual partners of child-bearing potential who are unwilling to follow
strict contraception requirements before entry and throughout the study,
up to and including the 30-day non-treatment follow-up period
Examples of acceptable contraception methods include:
- estrogen-gestagen based contraceptives associated with inhibition of
ovulation (oral, intravaginal, transdermal),
- gestagen-only based contraceptives associated with inhibition of
ovulation (oral, injectable, implantable),
- intra-uterine devices (IUDs),
- intra-uterine hormone-releasing systems (IUSs),
- bilateral tubal occlusion
- vasectomized partner
- sexual abstinence
o. Major surgery without full recovery or major surgery within 3 weeks
before planned randomization
p. Uncontrolled hypertension
q. New onset seizures (within 3 months before planned randomization)
or poorly controlled seizures
r. Any other concurrent investigational agent or chemotherapy,
radiotherapy, immunotherapy, or corticosteroids (prednisone up to 20
mg/day or its equivalent is permitted for chronic conditions)
s. Treatment with cytarabine at any dose, lenalidomide, or any other
therapy targeted to the treatment of MDS (other than growth factors and
other supportive care measures) within 4 weeks of planned
randomization
t. Investigational therapy within 4 weeks of planned randomization
u. Psychiatric illness or social situation that would limit the patient's
ability to tolerate and/or comply with study requirements.
E.5
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method