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INSPIRE: A phase III, international, randomized, controlled study of rigosertib vs. physician's choice of treatment in patients with myelodysplastic syndrome (MDS) after failure of a hypomethylating agent

Description

This is a phase III, open-label, randomized (2:1), controlled, international study for patients with MDS classified as RAEB-1, RAEB-2 or RAEB-t after failure of treatment with azacitidine (AZA) or decitabine (DAC).

Status

Accepting new patients

Primary Study Objective(s)

The primary objective of this study is to compare the overall survival of patients in the rigosertib group vs. the physician’s choice group in all patients and in a subgroup of patients with IPSS-R very high risk.

Core eligibility

Note: This is only a partial list of eligibility criteria.

Including patients who:

  • Have myelodysplastic syndromes classified as follows:
    • RAEB-1 per World Health Organization (WHO) MDS criteria (5 percent to <10 percent BM blasts)
    • RAEB-2 per WHO MDS criteria (10 percent to <20 percent BM blasts)
    • RAEB-t per French-American-British (FAB) classification (20 percent to 30 percent BM blasts)
  • Have at least one cytopenia (ANC < 1800/µL or platelet count < 100,000/µL or hemoglobin [Hgb] < 10 g/dL)
  • Have 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, according to 2006 IWG, after at least six four-week cycles of AZA or either four four-week or four six-week cycles of DAC administered or relapse after initial complete or partial response or HI, according to 2006 IWG criteria
  • Have a duration of prior HMA therapy less than nine months and/or total less than nine cycles of prior HMA therapy in less than 12 months
  • Had a last dose of AZA or DAC within six months before the planned date of randomization; however, must be off these treatments for more than four weeks before randomization
  • Failed to respond to, relapsed following, not eligible for, or opted not to participate in allogeneic stem cell transplantation
  • Have had no treatments for MDS (including AZA and DAC) for more than 4 weeks before randomization; growth factors (G-CSF, erythropoietin and thrombopoietin) and transfusions are allowed before and during the study as clinically indicated
  • Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2
  • Have a willingness to adhere to protocol prohibitions and restrictions
  • Signed an informed consent form to indicate patient's understanding study's purpose and procedures and willingness to participate (Should a patient be incapable of giving consent, the patient's legally authorized representative as defined by local regulation must give consent. However, should a patient, in any manner, choose not to participate this takes precedence and will be respected.)
  • Have 5q- syndrome and have failed to respond to or progressed on treatment with lenalidomide, where available and indicated

Excluding patients who:

  • Had previous participation in a clinical study of IV or oral rigosertib (Patients who failed screening for other rigosertib studies may be screened for participation.)
  • Are eligible to receive induction chemotherapy, such as seven to 10 days of cytosine arabinoside plus two-to three days of an anthracycline, or high-dose cytarabine
  • Are suitable candidates 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)
  • Had any active malignancy within the past year, except basal cell or squamous cell skin cancer or carcinoma in situ that is unlikely to progress in two years
  • Uncontrolled intercurrent illness including, but not limited to, symptomatic congestive heart failure or unstable angina pectoris
  • Have an active infection not adequately responding to appropriate therapy
  • Have total bilirubin ≥1.5 mg/dL not related to hemolysis or Gilbert's disease
  • Have alanine transaminase (ALT)/aspartate transaminase (AST) ≥2.5 x upper limit of normal (ULN)
  • Have serum creatinine ≥2.0 mg/dL or eGFR (estimated Glomerular Filtration Rate) < 40 mL/min
  • Have known active HIV, hepatitis B or hepatitis C, where active is defined as follows:
    • HIV or hepatitis C - presence of viral load
    • Hepatitis B - antigen positive
  • Have uncorrected hyponatremia (defined as serum sodium value of <130 mEq/L)
  • Are a female of child-bearing potential or a male 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 in accordance with an individual's lifestyle
  • Are pre-menopausal and not surgically sterilized females of child-bearing potential, who are breast-feeding or have a positive blood beta-human chorionic gonadotropin pregnancy test at screening
  • Had major surgery without full recovery or within three weeks before planned randomization
  • Have uncontrolled hypertension
  • Have had new onset seizures within three months before planned randomization or poorly controlled seizures
  • Have 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)
  • Had 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 four weeks of planned randomization
  • Have had investigational therapy within four weeks of planned randomization
  • Have psychiatric illness or social situation that would limit the patient's ability to tolerate and/or comply with study requirements
  • Have been previously diagnosed with AML, defined as a bone marrow or peripheral blood blast percentage of more than 30 percent
     

Accepting new patients

 

Learn more at

clinicaltrials.gov

 

Principal Investigator(s)