Efficacy and Safety of IV Rigosertib in MDS Patients With Excess Blasts Progressing After Azacitidine or Decitabine

NCT ID: NCT01928537

Last Updated: 2020-06-30

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 67 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-08-31
• Study Completion Date: 2017-06-29

Brief Summary

This study will examine the effect intravenously administered rigosertib has on the relationship between bone marrow blasts response and overall survival in myelodysplastic syndromes (MDS) patients who have 5-30% bone marrow blasts and who progressed on or after treatment with azacitidine or decitabine.

Conditions

Myelodysplastic Syndromes; Refractory Anemia With Excess Blasts; Chronic Myelomonocytic Leukemia; Cytopenia

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

rigosertib sodium

Rigosertib sodium will be administered as a 72-hr continuous intravenous infusion consisting of 3 consecutive doses of 1800 mg over 24 hours on Days 1, 2, and 3 of a 14-day cycle for the first 8 cycles and then on Days 1, 2, and 3 of a 28-day cycle for the following cycles.

Group Type: EXPERIMENTAL

rigosertib sodium

Intervention Type: DRUG

Interventions

rigosertib sodium

Intervention Type: DRUG

Other Intervention Names

ON 01910.Na; SyB L-1101

Eligibility Criteria

Inclusion Criteria

• Diagnosis of MDS confirmed within 6 weeks prior to Screening according to WHO criteria or French-American-British (FAB) classification.
• 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/μL
• RAEB-t (20% to 30% BM blasts), meeting the following criteria: WBC < 25,000/μL at study entry; or, Stable White Blood Cell (WBC) at least 4 weeks prior to Screening and not requiring intervention for WBC control with hydroxyurea, chemotherapy, or leukopheresis.
• At least one cytopenia (Absolute Neutrophil Count (ANC) < 1800/μL or Platelet (PLT) count < 100,000/μL or hemoglobin (Hgb) < 10 g/dL).
• Progression (according to 2006 IWG criteria) at any time after initiation of subcutaneous or intravenous azacitidine or decitabine 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 PLT; Decrease in Hgb concentration by ≥ 2 g/dL; or, 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.
• Has failed to respond to, relapsed following, not eligible, or opted not to participate in bone marrow transplantation.
• Off all other treatments for MDS for at least 4 weeks, except for azacitidine or decitabine. Filgrastim (G-CSF) and erythropoietin are allowed before and during the study as clinically indicated.
• No medical need for induction chemotherapy.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2.
• Willing to adhere to the prohibitions and restrictions specified in this protocol.
• Patient must signed an informed consent form.

Exclusion Criteria

• Previous participation in a clinical study of IV or oral rigosertib.
• Anemia due to factors other than MDS (including hemolysis or gastrointestinal [GI] bleeding) unless stabilized for 1 week after RBC transfusion.
• 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.
• Active infection not adequately responding to appropriate therapy.
• Total bilirubin ≥ 1.5 mg/dL not related to hemolysis or Gilbert's disease.
• ALT/AST ≥ 2.5 x upper limit of normal (ULN).
• Serum creatinine ≥ 2.0 mg/dL.
• Ascites requiring active medical management including paracentesis, or hyponatremia (defined as serum sodium value of <130 mEq/L).
• Female patients who are pregnant or lactating.
• Patients who are unwilling to follow strict contraception requirements.
• Female patients with reproductive potential who do not have a negative urine beta-human chorionic gonadotropin (βHCG) pregnancy test at Screening.
• Major surgery without full recovery or major surgery within 3 weeks of Baseline/Cycle 1 Day 1 visit.
• Uncontrolled hypertension (defined as a systolic pressure ≥160 mmHg and/or a diastolic pressure ≥ 110 mmHg).
• New onset seizures (within 3 months prior to Baseline) or poorly controlled seizures.
• Any other concurrent investigational agent or chemotherapy, radiotherapy, or immunotherapy.
• Prior treatment with low-dose cytarabine during the past 2 years.
• Investigational therapy within 4 weeks of Baseline/Day 1 visit.
• Psychiatric illness or social situation that would limit the patient's ability to tolerate and/or comply with study requirements.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Traws Pharma, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Steven M. Fruchtman, MD

Role: STUDY_CHAIR

Traws Pharma, Inc.

Locations

Stanford University Cancer Center

Stanford, California, United States

Rush University Medical Center

Chicago, Illinois, United States

University of Chicago Medicine

Chicago, Illinois, United States

University of Kansas Cancer Center and Medical Pavilion

Westwood, Kansas, United States

Greenbaum Cancer Center University of Maryland

Baltimore, Maryland, United States

Dana Farber Cancer Institute

Boston, Massachusetts, United States

Mayo Clinic

Rochester, Minnesota, United States

Mount Sinai Medical Center

New York, New York, United States

Columbia University Medical Center

New York, New York, United States

New York Presbyterian Hospital-Weill Cornell Medical College

New York, New York, United States

Montefiore Medical Center

The Bronx, New York, United States

University of Texas Southwestern Medical Center-Parkland Hospital

Dallas, Texas, United States

University of Texas Southwestern Medical Center

Dallas, Texas, United States

MD Anderson Cancer Center

Houston, Texas, United States

Royal Adelaide Hospital

Adelaide, South Australia, Australia

Monash Health, Monash Medical Centre

Clayton, Victoria, Australia

Peter MacCallum Cancer Center

East Melbourne, Victoria, Australia

Royal Melbourne Hospital

Parkville, Victoria, Australia

Rigshospitalet, Department of Hematology

Copenhagen, Capital Region, Denmark

Aarhus University Hospital

Aarhus, Jylland, Denmark

Hôpital Saint-Louis, Service d'Hématologie

Paris, IDF, France

Institute Paoli Calmettes

Marseille, , France

Universitätsklinikum Frankfurt, Goethe Universität

Frankfurt am Main, Hesse, Germany

Universitätsklinikum Köln Klinik I für Innere Medizin

Cologne, , Germany

University Hospital Carl Guslav Carus

Dresden, , Germany

Marien Hospital, Onkologie

Düsseldorf, , Germany

Universitätsmedizin Göttingen

Göttingen, , Germany

Technische Universität München, III. Medizinische Klinik

München, , Germany

Azienda Ospedaliero-Universitaria Careggi

Florence, , Italy

AOU Maggiore della Carità, SCUD Ematologia

Novara, , Italy

Policlinico Umberto 1, Universita "Sapienza"

Rome, , Italy

Hospital Universitário de Salamanca

Salamanca, , Spain

Skåne University Hospital,

Lund, Skåne County, Sweden

Sahlgrenska University Hospital

Gothenberg, Västra Götalandsregionen, Sweden

Karolinska University Hospital, Huddinge

Stockholm, , Sweden

Countries

United States; Australia; Denmark; France; Germany; Italy; Spain; Sweden

References

Olnes MJ, Shenoy A, Weinstein B, Pfannes L, Loeliger K, Tucker Z, Tian X, Kwak M, Wilhelm F, Yong AS, Maric I, Maniar M, Scheinberg P, Groopman J, Young NS, Sloand EM. Directed therapy for patients with myelodysplastic syndromes (MDS) by suppression of cyclin D1 with ON 01910.Na. Leuk Res. 2012 Aug;36(8):982-9. doi: 10.1016/j.leukres.2012.04.002. Epub 2012 Apr 21.

Reference Type: BACKGROUND

PMID: 22524974 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 21924492 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 24777753 (View on PubMed)

Al-Kali A. Relationship of bone marrow blast (BMBL) response to overall survival (OS) in a multicenter study of rigosertib (Rigo) in patients (pts) with myelodysplastic syndrome (MDS) with excess blasts progressing on or after treatment with a hypomethylating agent (HMA). Journal of Clinical Oncology 2017 35:15_suppl, 7056-7056 ASCO 2017

Reference Type: 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.

Reference Type: RESULT

Other Identifiers

2013-001124-19

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

Onconova 04-24

Identifier Type: -

Identifier Source: org_study_id