Phase III, International, Randomized, Controlled Study of Rigosertib versus Physician’s Choice of Treatment in Patients with Myelodysplastic Syndrome after Failure of a Hypomethylating Agent
- Conditions
- D46Myelodysplastic syndromes
- Registration Number
- DRKS00011259
- Lead Sponsor
- Onconova Therapeutics, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- 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
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
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 (or patient’s legally authorized representative) must have 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.
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 plus 2-3
days of an anthracycline, or high-dose cytarabine (HDAC)
c. Patient previously diagnosed with AML (defined as a bone marrow blast percentage of
>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
k. Known HIV, hepatitis B or hepatitis C
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 (ßHCG)
pregnancy test at Screening
n. Female patients of child-bearing potential and male patients with 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
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.
Study & Design
- Study Type
- interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method To compare the overall survival (OS) of patients in the rigosertib group vs the Physician’s<br>Choice group, in all patients and in a subgroup of patients with IPSS-R very high risk. Post-treatment Follow-up: All patients will have monthly follow-up for transformation to AML or survival until death.
- Secondary Outcome Measures
Name Time Method To compare rigosertib to Physician’s Choice with regard to the following:<br>o Overall survival of patients with monosomy 7 chromosomal aberrations<br>o Overall survival of patients with trisomy 8 chromosomal aberrations<br>o Overall response according to 2006 International Working Group (IWG) criteria<br>o Quality-of-life (QoL) scores using the EuroQol EQ-5D Questionnaire (timepoints: Baseline, Q4W (+/- 2 days), End-of-treatment)<br>o Overall bone marrow blast response according to 2006 IWG criteria<br>o Hematologic improvement (HI) (erythroid, platelet or neutrophil response) according<br>to 2006 IWG criteria<br>Post-treatment Follow-up: All patients will have monthly follow-up for transformation to AML or survival until death.