Overview

This trial is active, not recruiting.

Conditions myelodysplastic syndrome, acute myeloid leukemia, chronic myelomonocytic leukemia
Treatments oral rigosertib, azacitidine
Phase phase 1/phase 2
Sponsor Onconova Therapeutics, Inc.
Start date August 2013
End date February 2017
Trial size 58 participants
Trial identifier NCT01926587, 2013-000673-72, Onconova 09-08

Summary

This study, as a Phase I/II clinical trial, has two parts. The objective in the first part of this study is to determine the largest dose of the experimental anti-cancer drug, oral rigosertib, that can be given safely in combination with azacitidine. Azacitidine is an approved drug used to treat patients with myelodysplastic syndrome (MDS). The second part of the study will assess if treatment with rigosertib (at the dose determined in the first part), in combination with azacitidine, has measurable effects in patients with MDS and other diseases. Safety of patients is an objective throughout both parts of the study.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Endpoint classification safety/efficacy study
Intervention model single group assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
Oral rigosertib will be administered twice a day (BID) in fasting conditions for weeks 1, 2, and 3 of a 4-week cycle. Starting on Day 1 of second week (Day 8) of the cycle, azacitidine will be administered by subcutaneous injection or intravenous infusion at the labeled daily dose of 75 mg/m2, for 7 days.
oral rigosertib ON 01910.Na
Oral rigosertib will be administered twice a day (BID) in fasting conditions for weeks 1, 2, and 3 of a 4-week cycle.
azacitidine Vidaza
Starting on Day 1 of second week (Day 8) of the cycle, azacitidine will be administered by subcutaneous injection or intravenous infusion at the labeled daily dose of 75 mg/m2, for 7 days.

Primary Outcomes

Measure
Dose escalation part of study: Number of patients in whom Dose a Limiting Toxicity (DLT) are observed
time frame: 28 days
Dose escalation part of study: Number of patients in whom adverse events are observed
time frame: Up to 48 weeks
In Phase 2 of study: Number of patients in whom adverse events are observed
time frame: Up to 48 weeks
In Phase 2 of study: Area Under the Curve (AUC)
time frame: Day 1 and Day 15
In Phase 2 of the study: Cmax
time frame: Days 1 and 15.

Secondary Outcomes

Measure
Number of patients with complete or partial response
time frame: Up to 48 weeks
Number of patients in whom improvements in absolute neutrophil count, platelet count, and erythroid responses are observed
time frame: Up to 48 weeks.

Eligibility Criteria

Male or female participants at least 18 years old.

Inclusion Criteria: - Diagnosis of MDS, CMML, or RAEB-t/non-proliferative AML (as defined by 20-30% BMBL, WBC ≤ 25,000 x 10^9/L and stable for at least 4 weeks without intervention) according to World Health Organization (WHO) criteria or French American British (FAB) classification either previously treated or previously untreated. The diagnosis must be confirmed via BM aspirate and/or biopsy within 6 weeks prior to Screening. Note: patients with RAEB-t/non-proliferative AML (as defined by 20-30% BMBL, WBC ≤ 25,000 x 10^9/L and stable for at least 4 weeks without intervention) are not eligible for the Phase II RPTD component of the study. - If the patient has been diagnosed with MDS, disease of patient must be classified as Int-1, Intermediate-2 (Int-2) or High-risk, according to International Prognosis Scoring System (IPSS) classification. Note: Only Int-2 or High-risk patients will be enrolled at French site. - Off all other treatments for MDS, CMML, or AML including an erythropoiesis-stimulating agent (ESA), for at least 4 weeks prior to Screening. Filgrastim (G-CSF) is allowed before and during the study, as clinically indicated. - For AML patients, no more than 1 prior salvage therapy. - Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2. - Willing to adhere to the prohibitions and restrictions specified in this protocol. - The patient must signed an informed consent form indicating that she/he understands the purpose of and procedures required for the study and is willing to participate in the study. Exclusion Criteria: - Prior treatment with rigosertib; - Anemia due to factors other than MDS, CMML, or AML (including hemolysis or gastrointestinal bleeding). - 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. - Active infection not adequately responding to appropriate therapy. - Total bilirubin ≥ 2.0 mg/dL not related to Gilbert's disease or hemolysis. - Alanine transaminase (ALT)/aspartate transaminase (AST) ≥ 2.5 x upper limit of normal (ULN). - Serum creatinine ≥ 2.0 mg/dL. - Ascites requiring active medical management including paracentesis. - Hyponatremia (defined as serum sodium value of < 130 mEq/L). - Female patients who are pregnant or lactating. - Female patients of childbearing potential and male patients with partners of childbearing potential who are unwilling to follow strict contraception requirements before entry and throughout the study, up to and including the 30-day nontreatment follow-up period. - Female patients with reproductive potential who do not have a negative blood or urine pregnancy test at Screening. - Major surgery without full recovery or major surgery within 3 weeks of Screening. - Uncontrolled hypertension (defined as a systolic pressure ≥ 160 mmHg and/or a diastolic pressure ≥ 110 mmHg). - New onset seizures (within 3 months prior to Screening) or poorly controlled seizures. - Any other investigational agent or chemotherapy, radiotherapy, or immunotherapy administered within 4 weeks prior to Screening. - Chronic use (˃ 2 weeks) of corticosteroids (˃ 10 mg/24 hr equivalent prednisone) within 4 weeks of Baseline/First Dose. - Investigational therapy within 4 weeks of Screening. - Psychiatric illness or social situation that would limit the patient's ability to tolerate and/or comply with study requirements. - Patients with RAEB-t/non-proliferative AML (as defined by 20-30% BMBL, WBC ≤ 25,000 x 10^9/L and stable for at least 4 weeks without intervention) are not eligible to participate in the Phase II RPTD portion of the study.

Additional Information

Official title A Phase I/II, Multi-center, Dose-escalating Study of the Tolerability, Pharmacokinetics, and Clinical Activity of the Combined Administration of Oral Rigosertib With Azacitidine in Patients With Myelodysplastic Syndrome or Acute Myeloid Leukemia
Description This will be a Phase I/II open-label, single-arm, dose-escalating, multicenter study in which patients with myelodysplastic syndrome (MDS), acute myeloid leukemia (AML), or chronic myelomonocytic leukemia (CMML) will receive subcutaneous (SC) or intravenous (IV) azacitidine per approved label in combination with oral rigosertib. The Phase I dose escalation portion of the study (3 to 18 patients) will follow a traditional 3+3 design, and will aim at determining the Maximum Tolerated Dose (MTD) and the Recommended Phase Two Dose (RPTD) for the combination regimen. The Phase II RPTD cohort (up to 28 evaluable patients) will be treated at the MTD/RPTD level, as determined during the escalation phase. Patients treated at the MTD/RPTD in the Phase I component of the study will be included in the Phase II component and evaluated for response.
Trial information was received from ClinicalTrials.gov and was last updated in November 2016.
Information provided to ClinicalTrials.gov by Onconova Therapeutics, Inc..