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

June 22, 2017 updated by: Onconova Therapeutics, Inc.

A Phase 1/2, Single-Arm Study To Assess The Efficacy and Safety Of 5-day Continuous Intravenous Dosing Of ON 01910.Na Administered Every 2 Weeks in Patients With Intermediate-1, Intermediate-2, or High Risk Myelodysplastic Syndrome (MDS)

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.

Study Overview

Status

Withdrawn

Conditions

Intervention / Treatment

Detailed Description

This is a single center, open label, phase 1/2 study in which two to thirty three patients with Intermediate-1, Intermediate-2, or High risk MDS will receive ON 01910.Na as a intravenous continuous infusion (IVCI) over 24 hours for 5 consecutive days every 2 weeks.

In the phase 1 component of this trial the maximum tolerated dose of ON1910.Na in patients with Intermediate-1, Intermediate-2 or High Risk myelodysplastic syndromes will be determined. A standard "3+3" dose escalation scheme will be followed with up to six patients treated at the 800 mg/m2/day dose level. Patients will be observed for 2 cycles before dose escalation occurs. If none of the initial three patients in the 800 mg/m2/day cohort experience dose-limiting toxicity (DLT), during the first two cycles, then a new cohort of three patients will be treated at the 1500 mg/m2/day dose level. If none of the initial three patients in the 1500 mg/m2/day cohort experience DLT during the first two cycles, three additional patients will be treated at the 1500 mg/m2/day level. If no more than one of the six patients at the 1500 mg/m2/day dose level experiences a DLT, then that dose level will be confirmed as the MTD and no further dose escalation will occur.

If one of the three patients in the 800 mg/m2/day cohort experiences DLT during the first two cycles, then up to three additional patients will be treated at the same dose level. Escalation to 1500 mg/m2/day will proceed if only one of the six patients experiences DLT at the 800 mg/m2/day dose level. If two or more patients in the 800 mg/m2/day cohort experience DLT during the first two cycles, then the maximum tolerated dose (MTD) will have been exceeded, no further dose escalation will occur, and a full safety review will determine if further enrollment of patients will proceed.

If the 800 mg/m2/day dose level is under consideration as the MTD (i.e. if ≥ 2 patients experience DLT at the 1500 mg/m2/day dose level), and only three patients were treated before escalation to 1500 mg/m2/day, then three additional patients will be accrued. If no more than one of the six patients at the 800 mg/m2/day dose level experiences a DLT, then that dose level will be confirmed as the MTD.

Once the phase 1 portion of the study is completed, accrual to the phase 2 portion will begin. Patients treated at the MTD during the phase 1 portion will be included in the phase 2 component and will be evaluated for response and secondary end points.

The total study duration is 29 weeks, which includes a 2-week screening phase, a 23-week dosing phase, and a 4-week follow-up phase that begins after the last dose of ON 01910.Na. Patients will be assessed for response and will undergo follow up.

Patients who drop out for any reason will not be replaced. Patients who achieve a complete or partial response or stabilization of their disease by week 25 are eligible to receive an additional 24 weeks of ON 01910.Na at the same dose they received during the first 24 weeks of treatment(800 or 1500 mg/m2/day IVCI for 5 days Q2W).

Study Type

Interventional

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • New York
      • New York, New York, United States, 10065
        • Memorial Sloan-Kettering Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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.
  • Treatment with myeloid growth factors or erythropoiesis stimulating agents (ESA) within 2 weeks of starting ON 01910.Na.
  • Treatment with standard MDS therapies or investigational therapy within 4 weeks of starting ON 01910.Na.
  • Psychiatric illness/social situations that would limit the patient's ability to tolerate and/or comply with study requirements.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Maximum tolerated dose (in Phase 1)
Time Frame: 1 month
1 month
Response according to International Working Group criteria (in Phase 2)
Time Frame: 2 to 3 months
2 to 3 months

Secondary Outcome Measures

Outcome Measure
Time Frame
Overall survival
Time Frame: 12 months
12 months
Response time
Time Frame: 2 - 6 months
2 - 6 months
IPSS score
Time Frame: 2 to 6 months
2 to 6 months
Neutrophil response
Time Frame: 2 to 6 months
2 to 6 months
Platelet response
Time Frame: 2 to 6 months
2 to 6 months
Erythroid response
Time Frame: 2 to 6 months
2 to 6 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Onconova Therapeutics, Inc.

Investigators

  • Principal Investigator: Virginia Klimek, MD, Memorial Sloan Kettering Cancer Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

March 1, 2009

Primary Completion (Anticipated)

June 1, 2010

Study Completion (Anticipated)

September 1, 2010

Study Registration Dates

First Submitted

March 19, 2009

First Submitted That Met QC Criteria

March 20, 2009

First Posted (Estimate)

March 23, 2009

Study Record Updates

Last Update Posted (Actual)

June 23, 2017

Last Update Submitted That Met QC Criteria

June 22, 2017

Last Verified

June 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • Onconova 04-11

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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