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A 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

Description

This is a Phase III, open-label, randomized, controlled, international study (approximately 100 sites). Approximately 225 patients < 80 years of age with MDS classified as RAEB-1, RAEB-2, or RAEB-t who received AZA or DEC for ≤ 9 months and had their last dose of AZA or DEC within 6 months prior to screening will be stratified by: - Very high risk (VHR) vs non-VHR per IPSS-R, and - Geographic region (North America vs Europe vs Asia; because approved products and standard of care may vary by region), and randomly assigned in a 2:1 ratio to one of the following 2 treatment groups: - Rigosertib 1800 mg/24 hr administered as a 72 hr CIV infusion on Days 1, 2, and 3 of a 2 week cycle for the first 8 cycles, and on Days 1, 2, and 3 of a 4-week cycle thereafter (N = approximately 150 patients); - Physician's Choice of alternative treatment, which may include any approved or standard-of-care therapy, based on frequently used treatment for MDS after receipt of HMAs (N = approximately 75 patients). Experimental therapies are not allowed on the PC arm. Patients will be treated until 2006 IWG progression criteria are met (ie, 50% increase of BM blasts or worsening of cytopenias) or until an unacceptable toxicity or intolerance. For all randomized patients who discontinue study treatment, subsequent therapies with their start and end dates, as well as survival time after treatment discontinuation, will be documented at least monthly until death. Patients in the PC group who progress will not be allowed to cross over to rigosertib. All patients in both treatment groups will be allowed, as medically justified, access to RBC and platelet transfusions and to growth factors (granulocyte colony-stimulating factor (G-CSF), erythropoietin, and thrombopoietin).

Phase

Phase 3 - a treatment has shown activity against a particular disease, where it is either added to existing treatment or compared to the standard treatment.

Inclusion and Exclusion Criteria

  • Inclusion Criteria:
  • MDS classified as follows:
  • RAEB-1 per World Health Organization (WHO) MDS criteria (5% to 9% BM blasts)
  • RAEB-2 per WHO MDS criteria (10% to 19% BM blasts)
  • RAEB-t per French-American-British (FAB) classification (20% to 30% BM blasts)
  • Diagnosis of MDS confirmed within 8 weeks prior to the Screening Visit
  • At least one cytopenia (ANC < 1800/µL or platelet count < 100,000/µL or hemoglobin [Hgb] < 10 g/dL)
  • Progression (according to 2006 IWG criteria) at any time after initiation of AZA or DEC 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 DEC administered or Relapse after initial complete or partial response or HI (according to 2006 IWG criteria)
  • Duration of prior HMA therapy ≤ 9 months
  • Last dose of AZA or DEC within 6 months before the planned date of randomization; however, must be off these treatments for ≥ 4 weeks before randomization
  • Has failed to respond to, relapsed following, not eligible for, or opted not to participate in allogeneic stem cell transplantation
  • Off all treatments for MDS (including AZA and DEC) for ≥ 4 weeks before randomization; growth factors (G-CSF, erythropoietin and thrombopoietin) and transfusions are allowed before and during the study as clinically indicated
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2
  • Willing to adhere to protocol prohibitions and restrictions
  • Patient (or a legally authorized representative) must sign informed consent form to indicate patient's understanding study's purpose and procedures and willingness to participate Exclusion Criteria:
  • Previous participation in a clinical study of IV or oral rigosertib; patients who failed screening for other rigosertib studies may be screened for participation
  • Eligible to receive induction chemotherapy, such as 7-10 days of cytosine arabinoside plus 2-3 days of an anthracycline, or high-dose cytarabine
  • Eligible to receive allogeneic stem cell transplantation
  • Any active malignancy within the past year, except basal cell or squamous cell skin cancer or carcinoma in situ of the cervix or breast
  • Uncontrolled intercurrent illness including, but not limited to, symptomatic congestive heart failure or unstable angina pectoris
  • Active infection not adequately responding to appropriate therapy
  • Total bilirubin ≥1.5 mg/dL not related to hemolysis or Gilbert's disease
  • Alanine transaminase (ALT)/aspartate transaminase (AST) ≥2.5 x upper limit of normal (ULN)
  • Serum creatinine ≥2.0 mg/dL
  • Known HIV, hepatitis B or hepatitis C
  • Uncorrected hyponatremia (defined as serum sodium value of <130 mEq/L)
  • 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
  • Female patients of child-bearing potential who are breast-feeding or have a positive blood beta-human chorionic gonadotropin pregnancy test at Screening
  • Major surgery without full recovery or within 3 weeks before planned randomization;
  • Uncontrolled hypertension
  • New onset seizures (within 3 months before planned randomization) or poorly controlled seizures
  • 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)
  • 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
  • Investigational therapy within 4 weeks of planned randomization
  • Psychiatric illness or social situation that would limit the patient's ability to tolerate and/or comply with study requirements.

Sites

Please contact the trial administrator to learn more about where you can participate in this trial. Please use the contact form on the right side.

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