Phase IIIB, Open-label, Multi-Center Study of the Efficacy and Safety of Rigosertib Administered as 72-hour Continuous Intravenous Infusions in Patients with Myelodysplastic Syndrome with Excess Blasts Progressing On or After Azacitidine or Decitabine

Study ID
STU 042013-057

Cancer Related
Yes

Healthy Volunteers
No

Study Sites

Contact
James Pond
214-648-7030
blake.pond@utsouthwestern.edu

Principal Investigator
Robert Collins

Summary

This will be a Phase iiiB open-label, multi-center, multi-national study (approximately 30-40 centers in the united States and Western europe). approximately 90 patients with MDS classified as RaeB-1, RaeB-2, refractory anemia with excess blasts in transformation (RaeB-t), or CMML who progressed on or after treatment with aZa or DeC administered during the past 2 years, will be enrolled to receive rigosertib as 72-hour CiV infusions of 1800 mg/24 hr 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.

Patients will remain treated on study until 2006 iWG progression criteria are met (ie, 50% increase of BMBL or worsening of cytopenias) or until death from any cause, whichever comes first.

Participant Eligibility

Male and female myelodysplastic syndrome (MDS) patients who meet all of the following criteria are eligible for enrollment in the trial:
1. >=18 years of age;
2. Diagnosis of MDS confirmed within 6 weeks prior to Screening according to World Health Organization (WHO) criteria or French-American-British (FAB) classification;
3. MDS classified as follows, according to WHO criteria and FAB classification:

* RAEB-1 (5% to 9% BM blasts)

* RAEB-2 (10% to 19% BM blasts)

* CMML (10% to 20% BM blasts) and white blood cells (WBC) < 13,000/[MICRO-SYMBOL]L

* RAEB-t (20% to 30% BM blasts), meeting the following criteria:
- WBC < 25 x 109/L at study entry
- Stable WBC at least 4 weeks prior to Screening and not requiring intervention for WBC control with hydroxyurea, chemotherapy, or leukophoresis;
4. At least one cytopenia (ANC < 1800/[MICRO-SYMBOL]L or PLT count < 100,000/[MICRO-SYMBOL]L or hemoglobin [Hgb] < 10 g/dL);
5. Progression (according to 2006 IWG criteria) at any time after initiation of subcutaneous or intravenous azacitidine (AZA) or decitabine (DEC) treatment per labeling during the past 2 years, defined as follows:

* For patients with [?] 5% BMBL, >= 50% increase in BMBL to [?] 5% BMBL

* For patients with 5-10% BMBL, >= 50% increase in BMBL to [?] 10% BMBL

* For patients with 10-20% BMBL, >= 50% increase in BMBL to [?] 20% BMBL

* For patients with 20-30% BMBL, >= 50% increase in BMBL to [?] 30% BMBL

* Any of the following:
- >= 50% decrease from maximum remission/response levels in granulocytes or platelets (PLT)
- Decrease in Hgb concentration by >= 2 g/dL
- Transfusion dependence, defined as administration of at least 4 RBC units in the past 8 weeks before Screening (patients must have Hgb values [?] 9 g/dL prior to transfusion to be considered), in the absence of another explanation.
6. Has failed to respond to, relapsed following, not eligible, or opted not to participate in BM transplantation;
7. Off all other treatments for MDS for at least 4 weeks, except for AZA or DEC. Filgrastim (G-CSF) and erythropoietin (EPO) are allowed before and during the study as clinically indicated;
8. No medical need for induction chemotherapy;
9. Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2;
10. Willing to adhere to the prohibitions and restrictions specified in this protocol;
11. Patient must signed an informed consent form (ICF) indicating that s/he understands the purpose of and procedures required for the study and is willing to participate.