Phase II Part 2 Expansion of Oral Rigosertib in Combination With Azacitidine
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT01926587|
Recruitment Status : Completed
First Posted : August 21, 2013
Last Update Posted : June 16, 2021
- Study Details
- Tabular View
- No Results Posted
- How to Read a Study Record
|Condition or disease||Intervention/treatment||Phase|
|Myelodysplastic Syndrome Acute Myeloid Leukemia Chronic Myelomonocytic Leukemia||Drug: oral rigosertib Drug: Azacitidine||Phase 1 Phase 2|
This will be a Phase I/II open-label, single-arm, dose-escalating, multicenter study, in three parts: Phase I Dose Escalation, Phase II, Part 1 RPTD Cohort, and Phase II, Part 2 Expansion, 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 first two parts of the study have been completed.
The Phase II Part 2 Expansion will enroll up to 40 patients, randomized 1:1 into 2 cohorts of up to 20 patients each, to receive 1120 mg of rigosertib over 24 hours: either 560 mg in the morning and 560 mg in the afternoon, or 840 mg in the morning and 280 mg in the afternoon. The afternoon dose in both cohorts must be administered at 3 PM (±1 hr) at least 2 hr after lunch. In the Phase II, Part 2 Expansion patients with RAEB t/non-proliferative AML will be eligible, however patients with CMML will not.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||45 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|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|
|Study Start Date :||August 2013|
|Actual Primary Completion Date :||December 8, 2020|
|Actual Study Completion Date :||February 16, 2021|
Experimental: Oral rigosertib plus azacitidine
Oral rigosertib will be administered twice a day 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.
Drug: oral rigosertib
Oral rigosertib will be administered twice a day in fasting conditions for weeks 1, 2, and 3 of a 4-week cycle.
Other Name: ON 01910.Na
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.
Other Name: Vidaza
- Dose escalation part of study: Number of patients in whom Dose a Limiting Toxicity (DLT) are observed [ Time Frame: 28 days ]Dose Limiting Toxicity is defined as Grade 3 or greater non-hematological toxicity or stomatitis and/or esophagitis/dysphagitis lasting longer than 3 days.
- Dose escalation part of study: Number of patients in whom adverse events are observed [ Time Frame: Up to 48 weeks ]Adverse events will be coded using the most recent version of the Medical Dictionary for Regulatory Activities (MedDRA) and summarized by system organ class (SOC), preferred term (PT), and worst Common Terminology Criteria for Adverse Events (CTCAE) Version 4 grade per patient.
- In Phase 2 of study: Number of patients in whom adverse events are observed [ Time Frame: Up to 48 weeks ]Adverse events will be coded using the most recent version of the Medical Dictionary for Regulatory Activities (MedDRA) and summarized by system organ class (SOC), preferred term (PT), and worst Common Terminology Criteria for Adverse Events (CTCAE) Version 4 grade per patient.
- In Phase 2 of study: Area Under the Curve (AUC) [ Time Frame: Day 1 and Day 15 ]The following time points will be used to collect samples to determine the AUC on Day 1 and 15: Pre-dose the first dose of the day and at 0.5, 1.0, 1.5, 2.0, 4.0, 6.0, and 8.0 hour post dose the first dose of the day.
- In Phase 2 of the study: Cmax [ Time Frame: Days 1 and 15. ]The following time points will be used to collect samples to determine the Cmax on Day 1 and 15: Pre-dose the first dose of the day and at 0.5, 1.0, 1.5, 2.0, 4.0, 6.0, and 8.0 hour post dose the first dose of the day.
- Number of patients with complete or partial response [ Time Frame: Up to 48 weeks ]Complete remission (CR) or partial remission (PR) or bone marrow CR according to 2006 International Working Group criteria.
- Number of patients in whom improvements in absolute neutrophil count, platelet count, and erythroid responses are observed [ Time Frame: Up to 48 weeks. ]Hematologic Improvement according to 2006 International Working Group criteria.
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
|Ages Eligible for Study:||18 Years and older (Adult, Older Adult)|
|Sexes Eligible for Study:||All|
|Accepts Healthy Volunteers:||No|
- 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 Part 1 RPTD component of the study and patients with CMML will not be eligible for Phase II Part 2 Expansion 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.
- 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 Part 1 RPTD component of the study and patients with CMML will not be eligible for Phase II Part 2 of the study.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01926587
|United States, Arizona|
|Banner MD Anderson Cancer Center|
|Gilbert, Arizona, United States, 85234|
|United States, California|
|City of Hope|
|Duarte, California, United States, 91010|
|Desert Hematology Oncology Medical Group, Inc.|
|Rancho Mirage, California, United States, 92270|
|United States, Illinois|
|Rush University Medical Center|
|Chicago, Illinois, United States, 60612|
|United States, Kansas|
|Cancer Center of Kansas|
|Wichita, Kansas, United States, 67214|
|United States, Missouri|
|Saint Louis University|
|Saint Louis, Missouri, United States, 63110|
|United States, New York|
|Roswell Park Cancer Institute|
|Buffalo, New York, United States, 14263|
|Mount Sinai Medical Center|
|New York, New York, United States, 10029|
|White Plains Hospital Center for Cancer Care|
|White Plains, New York, United States, 10601|
|United States, South Carolina|
|Carolina Blood and Cancer Care Associates|
|Rock Hill, South Carolina, United States, 29732|
|United States, Texas|
|The University of Texas MD Anderson Cancer Center|
|Houston, Texas, United States, 77030|
|United States, Wisconsin|
|Froedtert Hospital and the Medical College of Wisconsin|
|Milwaukee, Wisconsin, United States, 53226|
|Hôpital St. Louis|
|Paris, France, 75475|
|Study Chair:||Steven M. Fruchtman, MD||Onconova Therapeutics, Inc.|
Publications of Results:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
|Responsible Party:||Onconova Therapeutics, Inc.|
|Other Study ID Numbers:||
2013-000673-72 ( EudraCT Number )
|First Posted:||August 21, 2013 Key Record Dates|
|Last Update Posted:||June 16, 2021|
|Last Verified:||June 2021|
Leukemia, Myeloid, Acute
Leukemia, Myelomonocytic, Chronic
Leukemia, Myelomonocytic, Juvenile
Neoplasms by Histologic Type
Bone Marrow Diseases
Molecular Mechanisms of Pharmacological Action
Protein Kinase Inhibitors