Efficacy and Safety of ON 01910.Na in Myelodysplastic Syndrome (MDS) Patients With Trisomy 8 or Classified as Intermediate-1, -2 or High Risk

NCT00906334 | Completed Phase 2

• 1 other identifier: Onconova 04-17
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 1

Brief Summary

This study will explore the efficacy and safety of a regimen of ON 01910.Na as a 48-hour continuous intravenous infusion once a week for 3 weeks of a 4-week cycle in MDS patients with Trisomy 8 or classified as Intermediate-1, -2 or High Risk who are not responding to current therapeutic options. The rationale for this trial is based upon data from laboratory studies with ON 01910.Na and upon activity that has been observed in other clinical trials with ON 01910.Na in patients with MDS.

Conditions

Myelodysplastic Syndrome

Keywords

Myelodysplastic Syndrome; Trisomy 8; Intermediate-2 Risk Group; High-Risk Group; azacitidine; azacytidine; Vidaza; decitabine; Dacogen

Outcome Measures

Primary Outcomes (2)

• Overall Response Rate (ORR)

  The Overall Response Rate is defined as the proportion of patients who achieve a Complete Response, a Partial Response, A Complete Bone Marrow Response or a Hematologic Improvement (HI) according to the 2006 International Working Group (IWG) criteria.

  29 weeks

• Number of patients with adverse events

  The NCI Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 will be used to determine the grade of adverse events.

  From date of signing informed consent until 30 days after last dose of study drug up to 29 weeks

Secondary Outcomes (12)

• Time to Overall Response

  29 weeks

• Duration of Response

  29 weeks

• Bone Marrow Complete Response

  Weeks 5, 13, 21 and 29

• Cytogenetic Response

  29 weeks

• Neutrophil Response

  29 weeks

Study Arms (2)

800 mg/m^2 ON 01910.Na

EXPERIMENTAL

800 mg/m\^2 ON 01910.Na administered as a continuous intravenous infusion (CIV) over 24 hours for 48 hours (i.e. 2 consecutive 24-hour infusions) every week for the first 3 weeks of 4-week cycle.

Drug: ON 01910.Na

1800 mg ON 01910.Na

EXPERIMENTAL

1800 mg ON 01910.Na administered as a continuous intravenous infusion (CIV) over 24 hours for 72 hours (i.e., 3 consecutive 24-hour infusions) every 2 weeks for the first four 2-week cycles and every 4 weeks afterwards.

Drug: ON 01910.Na

Interventions

ON 01910.Na DRUG

The original dosing regimen was 800 mg/m\^2 ON 01910.Na.

Also known as: rigosertib

800 mg/m^2 ON 01910.Na

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of MDS confirmed within 2 weeks prior to study entry according to the World Health Organization (WHO) Criteria or the French-American-British (FAB) Classification.
• Trisomy 8 cytogenetics (simple or combined to other karyotypes) or patient classified as Intermediate-1 with bone marrow blasts equal to or greater than 5%, Intermediate-2 or High Risk MDS according to the IPSS score, or Patients with peripheral blood blasts equal to or greater than 5%.
• At least one cytopenia (Absolute Neutrophil Count \< 1800/µl or Platelet Count \<100,000/µl or Hemoglobin \< 10 g/dL).
• Failure of, or insufficient response to Azacytidine or Decitabine administered for 4 to 6 cycles in patients classified as Intermediate-2 or High risk or to Erythrocyte stimulating agents (failure or insufficient response defined as transfusion dependence or Hemoglobin remaining below 10 g/dl) in Low or Intermediate-1 Risk Trisomy 8 patients.
• Failed to respond to, relapsed following, or opted not to participate in bone marrow transplantation.
• Off all other treatments for MDS (including filgrastim (G-CSF) and erythropoietin) for at least four weeks. As an exception, filgrastim (G-CSF) can be used before, during and after the protocol treatment for patients with documented febrile neutropenia (\< 500/µl).
• ECOG Performance Status 0, 1 or 2.
• Willing to adhere to the prohibitions and restrictions specified in this protocol.
• Patient (or his/her legally authorized representative) must have signed an informed consent document indicating that he/she understands the purpose of and procedures required for the study and is willing to participate in the study.

You may not qualify if:

• Anemia due to factors other than MDS (including hemolysis or gastrointestinal bleeding).
• Hypoplastic MDS (cellularity \<10%).
• Any active malignancy within the past year except basal cell or squamous cell skin cancer or carcinoma in situ of the cervix or breast.
• History of HIV-1 seropositivity.
• Uncontrolled intercurrent illness including, but not limited to symptomatic congestive heart failure, unstable angina pectoris or cardiac arrhythmia.
• Active infection not adequately responding to appropriate therapy.
• Total bilirubin \> 1.5 mg/dL not related to hemolysis or Gilbert's disease, ALT or AST \> 2 X ULN.
• Serum creatinine \> 2.0 mg/dL or calculated creatinine clearance \< 60 ml/min/1.73 m\^2.
• Ascites requiring active medical management including paracentesis, or hyponatremia (defined as serum sodium value of \<134 Meq/L).
• Women patients who are pregnant or lactating; Male patients with female sexual partners who are unwilling to follow the strict contraception requirements described in this protocol; Patients who do not agree to use adequate contraceptive \[including prescription oral contraceptives (birth control pills), contraceptive injections, intrauterine device (IUD), double-barrier method (spermicidal jelly or foam with condoms or diaphragm), contraceptive patch, or surgical sterilization\] before entry and throughout the study; Female patients with reproductive potential who do not have a negative serum beta-HCG pregnancy test at screening.
• Major surgery without full recovery or major surgery within 3 weeks of ON 01910.Na treatment start.
• Uncontrolled hypertension (defined as a systolic pressure equal to or greater than 160 mmHg and/or a diastolic pressure equal to or greater than 110 mmHg).
• New onset seizures (within 3 months prior to the first dose of ON 01910.Na) or poorly controlled seizures
• Any concurrent investigational agent or chemotherapy, radiotherapy or immunotherapy.
• Treatment with standard MDS therapies or investigational therapy within 4 weeks of starting ON 01910.Na.

Sponsors & Collaborators

• Traws Pharma, Inc.: lead

Study Sites (1)

Stanford Cancer Center

Stanford, California, 94305, United States

Location

Related Publications (4)

• Seetharam M, Fan AC, Tran M, Xu L, Renschler JP, Felsher DW, Sridhar K, Wilhelm F, Greenberg PL. Treatment of higher risk myelodysplastic syndrome patients unresponsive to hypomethylating agents with ON 01910.Na. Leuk Res. 2012 Jan;36(1):98-103. doi: 10.1016/j.leukres.2011.08.022. Epub 2011 Sep 14.

  PMID: 21924492 RESULT

• Silverman LR, Greenberg P, Raza A, Olnes MJ, Holland JF, Reddy P, Maniar M, Wilhelm F. Clinical activity and safety of the dual pathway inhibitor rigosertib for higher risk myelodysplastic syndromes following DNA methyltransferase inhibitor therapy. Hematol Oncol. 2015 Jun;33(2):57-66. doi: 10.1002/hon.2137. Epub 2014 Apr 29.

  PMID: 24777753 RESULT

• Navada SC, Silverman LR. The safety and efficacy of rigosertib in the treatment of myelodysplastic syndromes. Expert Rev Anticancer Ther. 2016 Aug;16(8):805-10. doi: 10.1080/14737140.2016.1209413. Epub 2016 Jul 15.

  PMID: 27400247 RESULT

• Garcia-Manero G, Fenaux P. Comprehensive Analysis of Safety: Rigosertib in 557 Patients with Myelodysplastic Syndromes (MDS) and Acute Myeloid Leukemia (AML). Blood Dec 2016, 128 (22) 2011; ASH 2016.

  RESULT

Related Links

• Link for Stanford Cancer Center

MeSH Terms

Conditions

Myelodysplastic Syndromes; Chromosome 8, trisomy

Interventions

ON 01910

Condition Hierarchy (Ancestors)

Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases

Study Officials

• Peter L. Greenberg, MD

  Stanford University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 19, 2009
• First Posted: May 21, 2009
• Study Start: May 1, 2009
• Primary Completion: November 1, 2013
• Study Completion: November 1, 2013
• Last Updated: June 26, 2017

Record last verified: 2017-06

Locations

US (1)