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

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

A Phase 2, Single-Arm Study To Assess The Efficacy and Safety Of 72-Hour Continuous Intravenous Dosing Of ON 01910.Na Administered Every Other Week in Myelodysplastic Syndrome Patients With Trisomy 8 or Classified as Intermediate-1, 2 or High Risk

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

This is a phase 2, study in which 14 MDS patients with Trisomy 8 or classified as Intermediate-1, -2 and High risk who meet all other inclusion/exclusion criteria will receive ON 01910.Na 800 mg/m^2/24h as an continuous intravenous infusion (CIV) over 48 hours once a week for 3 weeks of a 4-week cycle. As of Amendment 3 to the Protocol, the regimen is changed to 1800 mg/24h for 72 hours every other week for the first four 2-week cycles and every 4 weeks afterwards. The total study duration is 31 weeks, which includes a 2-week screening phase, a 27-week dosing phase, and a 4-week follow-up phase that begins after the last dose of ON 01910.Na. Beginning at week 4, and every 2 weeks thereafter, patients will be assessed for response. Patients who drop out for any reason will not be replaced. Patients who achieve by week 29 a complete or partial response or stabilization of their disease are eligible to receive an additional 24 weeks of ON 01910.Na 1800 mg/24 h over 72 hours per week of a 4-week cycle.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
14

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

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
    • California
      • Stanford, California, United States, 94305
        • Stanford 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

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

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 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.

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 > 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.
  • 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: Non-Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: 800 mg/m^2 ON 01910.Na
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
The original dosing regimen was 800 mg/m^2 ON 01910.Na.
Other Names:
  • rigosertib
Drug: ON 01910.Na
Per Amendment 3 to the Protocol, the dosing regimen was changed to 1800 mg ON 01910.Na. Patients enrolled at the original dosing regimen could choose to remain in the original regimen or switch to the new regimen.
Other Names:
  • rigosertib
Experimental: 1800 mg ON 01910.Na
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
The original dosing regimen was 800 mg/m^2 ON 01910.Na.
Other Names:
  • rigosertib
Drug: ON 01910.Na
Per Amendment 3 to the Protocol, the dosing regimen was changed to 1800 mg ON 01910.Na. Patients enrolled at the original dosing regimen could choose to remain in the original regimen or switch to the new regimen.
Other Names:
  • rigosertib

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Overall Response Rate (ORR)
Time Frame: 29 weeks
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
Time Frame: From date of signing informed consent until 30 days after last dose of study drug up to 29 weeks
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 Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Time to Overall Response
Time Frame: 29 weeks
Time to Overall Response is calculated from date of first study drug administration to date of first occurrence of any of the following responses: Complete Response (CR), Partial Response (PR), Marrow Complete Response (BMCR) or Hematologic Improvement (HI) as defined by the 2006 International Working Group (IWG) criteria.
29 weeks
Duration of Response
Time Frame: 29 weeks
Duration of response is calculated from date of first occurrence of any of the following responses: Complete Response (CR), Partial Response (PR), Marrow Complete Response (BMCR) or Hematologic Improvement (HI) as defined by the 2006 International Working Group (IWG) criteria) until the date of disease progression. Patients who did not have disease progression are censored at the last bone marrow or bone marrow morphology assessment date.
29 weeks
Bone Marrow Complete Response
Time Frame: Weeks 5, 13, 21 and 29
The proportion of patients who achieve a Bone Marrow Complete Response (BMCR) according to 2006 International Working Group (IWG) criteria. Bone marrow blasts are determined in bone marrow differential count.
Weeks 5, 13, 21 and 29
Cytogenetic Response
Time Frame: 29 weeks
Cytogenetic Response is defined as the number of patients who achieve a cytogenic response according to 2006 International Working Group criteria. Complete response is defined as the disappearance of the chromosomal abnormality without appearance of new ones. Partial response is defined as at least 50% reduction of the chromosomal abnormality.
29 weeks
Neutrophil Response
Time Frame: 29 weeks
The number of patients who achieve a Neutrophil Response according to 2006 International Working Group (IWG). Neutrophil Response is defined as at least a 100% increase and an absolute increase greater than 0.5 x 10^9/L. Pretreatment values must be less than 1.0 x 10^9/L.
29 weeks
Platelet Response
Time Frame: 29 weeks
The number of patients who achieve a Platelet Response according to 2006 International Working Group (IWG). Platelet Response is defined as an absolute of greater than or equal to 30 x 10^9 for patients starting with less than 20 x 10^9/L. increase and an absolute increase greater than 0.5 x 10^9/L. Pretreatment values must be less than 1.0 x 10^9/L.
29 weeks
Erythroid Response
Time Frame: 29 weeks
The number of patients who achieve an Erythroid Response according to 2006 International Working Group (IWG). Erythroid Response is defined as a Hgb increase equal to or greater than 1.5 g/dL and a relevant reduction of units of red blood cells (RBC) transfusions by an absolute number of at least 4 RBC transfusions/8 weeks compared with the pretreatment transfusion number in the previous 8 wells. Only RBC transfusions given for a Hgb of 9.0 g/dL or lower pretreatment will count in the RBC transfusion response evaluation. Pretreatment values of Hgb must be lower than 11 g/dL.
29 weeks
Time to Disease Progression
Time Frame: 29 weeks
Time to Disease Progression is calculated from date of first dose of study drug administration to date of disease progression recorded on the hematology response assessment clinical report form.
29 weeks
Time to Acute Myeloid Leukemia (AML) Progression
Time Frame: 29 and 53 weeks
Time to Acute Myeloid Leukemia (AML) Progression is calculated from date of first study drug administration to date of AML progression recorded on the Off Study Summary clinical report form. Patients who do not have AML disease progression are censored at the last bone marrow or bone marrow morphology assessment date.
29 and 53 weeks
Overall Survival
Time Frame: 29 and 53 weeks
Overall Survival is calculated from date of first study drug administration to date of death. In event of no death prior to study termination or data analysis cutoff, overall survival is censored at the last known date patient was alive
29 and 53 weeks
Proportion of patients who achieve a Complete Hematologic Response
Time Frame: Up to 29 weeks
The proportion of patients who achieve a Complete Remission (CR) Hematologic Response according to 2006 International Working Group (IWG) criteria. Bone marrow blasts are determined in bone marrow differential count.
Up to 29 weeks
The proportion of patients who achieve a Partial Remission (CR)
Time Frame: Up to 29 weeks
The proportion of patients who achieve a Partial Remission (PR) Hematologic Response according to 2006 International Working Group (IWG) criteria. Bone marrow blasts are determined in bone marrow differential count.
Up to 29 weeks

Collaborators and Investigators

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

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Onconova Therapeutics, Inc.

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Peter L. Greenberg, MD, Stanford University

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

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
May 1, 2009

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
November 1, 2013

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
November 1, 2013

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
May 19, 2009

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 20, 2009

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
May 21, 2009

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
June 26, 2017

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 22, 2017

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
June 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • Onconova 04-17

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