Efficacy and Safety of 5-day Dosing of ON 01910.Na in Intermediate-1,-2, or High Risk Myelodysplastic Syndrome (MDS)

NCT00867061 | Withdrawn Phase 1

• 1 other identifier: Onconova 04-11
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

For MDS patients who have not responded to or have progressed after an initial response to DNA methyltransferase inhibitors (DNMTI) and are not stem cell transplant candidates, therapeutic options are limited. Participation in clinical trials such as this one may be considered. The specific objectives of this trial are to find out which dose of ON 01910.Na can be safety given to MDS patients and then find out if this dose of drug has any beneficial effects on the patients' disease. ON 01910.Na is a new, experimental drug; the reason for doing this trial is based on the anti-cancer activity of ON 01910.Na that has been observed in laboratory experiments and in early clinical trials.

Conditions

Myelodysplastic Syndrome

Keywords

Myelodysplastic; IPSS Intermediate 1; IPSS Intermediate 2; IPSS High risk

Outcome Measures

Primary Outcomes (2)

• Maximum tolerated dose (in Phase 1)

  1 month

• Response according to International Working Group criteria (in Phase 2)

  2 to 3 months

Secondary Outcomes (6)

• Response time

  2 - 6 months

• IPSS score

  2 to 6 months

• Neutrophil response

  2 to 6 months

• Platelet response

  2 to 6 months

• Erythroid response

  2 to 6 months

Interventions

ON 01910.Na Concentrate DRUG

5-day continuous intravenous dosing of ON 01910.Na given every 2 weeks (1 cycle) at a dose of 800 mg/m2/day or 1500mg/m2/day for up to 24 cycles.

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 4 weeks prior to study entry according to the World Health Organization (WHO) Criteria or the French-American-British (FAB) Classification.
• IPSS score of at least 0.5 (Intermediate-1, Intermediate-2 or High Risk MDS)
• Failure of, or insufficient response to 5-azacitidine or decitabine administered for 4 to 6 cycles.
• 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 2 weeks, and off standard or investigational MDS therapies for four weeks.
• ECOG Performance Status 0, 1 or 2.
• 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 for female patients of reproductive potential.
• Female patients with reproductive potential must have a negative serum beta-HCG pregnancy test at screening.
• 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 ≥ 1.5 mg/dL or calculated creatinine clearance ≤ 60 ml/min/1.73 m2
• Ascites requiring active medical management including paracentesis, or hyponatremia (defined as serum sodium value of \<134 Meq/L).
• Female 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.
• Major surgery without full recovery or major surgery within 3 weeks of ON 01910.Na treatment start.
• Uncontrolled hypertension (defined as a systolic pressure ≥ 160 and/or a diastolic pressure ≥ 110).
• 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.

Sponsors & Collaborators

• Traws Pharma, Inc.: lead

Study Sites (1)

Memorial Sloan-Kettering Cancer Center

New York, New York, 10065, United States

Location

Related Publications (6)

• Jimeno A, Chan A, Cusatis G, Zhang X, Wheelhouse J, Solomon A, Chan F, Zhao M, Cosenza SC, Ramana Reddy MV, Rudek MA, Kulesza P, Donehower RC, Reddy EP, Hidalgo M. Evaluation of the novel mitotic modulator ON 01910.Na in pancreatic cancer and preclinical development of an ex vivo predictive assay. Oncogene. 2009 Jan 29;28(4):610-8. doi: 10.1038/onc.2008.424. Epub 2008 Nov 24.

  PMID: 19029951 BACKGROUND

• Cheson BD, Bennett JM, Kantarjian H, Pinto A, Schiffer CA, Nimer SD, Lowenberg B, Beran M, de Witte TM, Stone RM, Mittelman M, Sanz GF, Wijermans PW, Gore S, Greenberg PL; World Health Organization(WHO) international working group. Report of an international working group to standardize response criteria for myelodysplastic syndromes. Blood. 2000 Dec 1;96(12):3671-4.

  PMID: 11090046 BACKGROUND

• Greenberg P, Cox C, LeBeau MM, Fenaux P, Morel P, Sanz G, Sanz M, Vallespi T, Hamblin T, Oscier D, Ohyashiki K, Toyama K, Aul C, Mufti G, Bennett J. International scoring system for evaluating prognosis in myelodysplastic syndromes. Blood. 1997 Mar 15;89(6):2079-88.

  PMID: 9058730 BACKGROUND

• Aarthi Shenoy, Loretta Pfannes, Francois Wilhelm, Manoj Maniar, Neal Young, and Elaine M Sloand Suppression of Cyclin D 1 (CD1) by ON 01910.Na Is Associated with Decreased Survival or Trisomy 8 Myelodysplastic Bone Marrow: A Potential Targetted Therapy for Trisomy 8 MDS. Blood (ASH Annual Meeting Abstracts), Nov 2008; 112: 1651.

  BACKGROUND

• Elaine M. Sloand, Loretta Pfannes, Ramana Reddy, Premkumar Reddy, Jerome S. Groopman, and Neal S. Young Suppression of Cyclin D1 by ON 01910.Na Is Associated with Decreased Survival of Trisomy 8 Myelodyplastic Bone Marrow Progenitors: A Potential Targetted Therapy. Blood (ASH Annual Meeting Abstracts), Nov 2007; 110: 822.

  BACKGROUND

• 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

• Website of trial study center. Provides cancer care information to healthcare professionals, researchers, patients, family members, and the public.

MeSH Terms

Conditions

Myelodysplastic Syndromes

Condition Hierarchy (Ancestors)

Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases

Study Officials

• Virginia Klimek, MD

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 19, 2009
• First Posted: March 23, 2009
• Study Start: March 1, 2009
• Primary Completion: June 1, 2010
• Study Completion: September 1, 2010
• Last Updated: June 23, 2017

Record last verified: 2017-06

Locations

US (1)