Guadecitabine (SGI-110) vs Treatment Choice in Adults With MDS or CMML Previously Treated With HMAs
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|ClinicalTrials.gov Identifier: NCT02907359|
Recruitment Status : Completed
First Posted : September 20, 2016
Last Update Posted : September 5, 2021
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|Condition or disease||Intervention/treatment||Phase|
|Myelodysplastic Syndromes Leukemia, Myelomonocytic, Chronic||Drug: Guadecitabine Other: Treatment Choice||Phase 3|
Multicenter, randomized, open-label, parallel-group study of guadecitabine vs Treatment Choice (TC). Approximately 408 subjects will be randomly assigned 2:1 to either guadecitabine or TC.
- Guadecitabine: approximately 272 subjects.
- TC: approximately 136 subjects.
Before randomization, the investigator will assign each subject to one of the following TC options:
- Low dose cytarabine (LDAC).
- Standard Intensive Chemotherapy (IC) of a 7+3 regimen.
- Best Supportive Care (BSC) only. BSC will be provided to all subjects as per standard and institutional practice. Subjects randomized to TC will not be allowed to cross over to guadecitabine. Data will be reviewed by an independent Data Monitoring Committee at regular intervals, primarily to evaluate safety during study conduct. Randomization will be stratified by disease category (MDS vs CMML), bone marrow (BM) blasts (BM blasts >10% vs BM blasts ≤10%), TC option (LDAC vs IC vs BSC), and study center region.
Guadecitabine: 60 mg/m2 given SC daily on Days 1-5 in 28-day cycles (delayed as needed to allow blood count recovery). Treatment should be given for at least 6 total cycles in the absence of unacceptable toxicity or disease progression requiring alternative therapy. Beyond 6 cycles, treatment should continue as long as the subject continues to benefit. BSC should be given according to standard and institutional practice.
Treatment Choice (TC): Before randomization, the investigator will assign each subject to one of the following TC options:
- Low dose cytarabine (LDAC) given as 20 mg/m2 SC or IV once daily for 14 days in 28-day cycles (delayed as needed to allow blood count recovery). Treatment should be given for at least 4 cycles in the absence of disease progression or unacceptable toxicity.
- Standard Intensive Chemotherapy (IC) of a 7+3 regimen: given as cytarabine 100-200 mg/m2/day given as continuous infusion for 7 days and an anthracycline given as per institutional standard practice such as daunorubicin (45-60 mg/m2/day), or idarubicin (9-12 mg/m2/day), or mitoxantrone (8-12 mg/m2/day) by intravenous infusion for 3 days.
- Best Supportive Care (BSC) only: given according to standard and institutional practice. BSC includes, but is not limited to blood transfusions (RBCs or platelets), growth factors including erythropoiesis stimulating agents (ESA), granulocyte stimulating factors (GSFs), iron chelating therapy, and broad spectrum antibiotics and/or antifungals.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||408 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase 3, Multicenter, Randomized, Open-Label Study of Guadecitabine (SGI-110) Versus Treatment Choice in Adults With Myelodysplastic Syndromes (MDS) or Chronic Myelomonocytic Leukemia (CMML) Previously Treated With Hypomethylating Agents|
|Actual Study Start Date :||October 2016|
|Actual Primary Completion Date :||March 31, 2020|
|Actual Study Completion Date :||November 30, 2020|
Guadecitabine 60 mg/m2 given subcutaneously daily on Days 1-5 in 28-day cycles. The total amount (in mg) of guadecitabine to be administered is determined by body surface area.
Guadecitabine regimen is 60 mg/m2 given SC daily on Days 1-5 in 28-day cycles (delayed as needed to allow blood count recovery). Treatment should be given for at least 6 total cycles in absence of unacceptable toxicity or disease progression requiring alternative therapy.
Other Name: SGI-110
Active Comparator: Treatment Choice
Other: Treatment Choice
- Overall survival [ Time Frame: 18 Months ]
- Transfusion independence [ Time Frame: 18 months ]
- Marrow complete response [ Time Frame: 18 months ]
- Survival rate [ Time Frame: 18 months ]
- Leukemia-free survival [ Time Frame: 18 months ]As described in Time Frame.
- Number of days alive and out of the hospital (NDAOH). [ Time Frame: 18 months ]
- Disease response [ Time Frame: 18 months ]
- Duration of response [ Time Frame: 18 months ]
- Number of transfusions [ Time Frame: 18 months ]
- Health-related quality of life [ Time Frame: 18 months ]
- Incidence and severity of adverse events. [ Time Frame: 18 months ]
- 30-day and 60-day all-cause mortality [ Time Frame: 18 months ]
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|
- Adult subjects ≥18 years of age who are able to understand and comply with study procedures, and provide written informed consent before any study-specific procedure.
- Cytologically or histologically confirmed diagnosis of MDS or CMML according to the 2008 World Health Organization (WHO) classification.
- Performance status (ECOG) of 0-2.
Previously treated MDS or CMML, defined as prior treatment with at least one hypomethylating agent (HMA; azacitidine and/or decitabine) for intermediate or high risk MDS or CMML whose disease progressed or relapsed as follows:
- Subject received HMA for at least 6 cycles and was still transfusion dependent (as defined in 5b below).
- Subject had disease progression prior to Cycle 6 defined as ≥50% increase in bone marrow blasts from pretreatment levels to >5%, or ≥2 g/dL reduction of Hgb from pretreatment levels with transfusion dependence after at least 2 cycles of HMA.
Other prior treatments for MDS such as lenalidomide, cytarabine, intensive chemotherapy, hydroxyurea, erythropoietin and other growth factors, or hematopoietic cell transplant (HCT) are allowed.
Subjects must have either:
- Bone marrow blasts >5% at randomization, OR
- Transfusion dependence, defined as having had transfusion (in the setting of active disease) of 2 or more units of RBC or platelets within 8 weeks prior to randomization.
- Creatinine clearance or glomerular filtration rate ≥30 mL/min estimated by the Cockroft-Gault (C-G) or other medically acceptable formulas such as MDRD (Modification of Diet in Renal Disease) or CKD-EPI (the Chronic Kidney Disease Epidemiology Collaboration).
- Women of childbearing potential must not be pregnant or breastfeeding and must have a negative pregnancy test at screening. Women of childbearing potential and men with female partners of childbearing potential must agree to practice 2 highly effective contraceptive measures of birth control and must agree not to become pregnant or father a child while receiving treatment with guadecitabine, LDAC, or IC and for at least 3 months after completing treatment.
- Subjects who have been diagnosed as having AML with peripheral blood or bone marrow blasts of ≥20%.
- Subjects who may still be sensitive to repeated treatment with decitabine or azacitidine such as subjects who had response to prior decitabine or azacitidine treatment, but relapsed >6 months after stopping treatment with these agents.
- Prior treatment with guadecitabine.
- Hypersensitivity to decitabine, guadecitabine, or any of their excipients.
- Second malignancy currently requiring active therapy, except breast or prostate cancer stable on or responding to endocrine therapy.
- Treated with any investigational drug within 2 weeks of the first dose of study treatment.
- Total serum bilirubin >2.5 ULN (except for subjects with Gilbert's Syndrome for whom direct bilirubin is <2.5×ULN), or liver cirrhosis or chronic liver disease Child-Pugh Class B or C.
- Known active HIV, HBV, or HCV infection. Inactive hepatitis carrier status or low viral hepatitis titer on antivirals is allowed.
- Known significant mental illness or other condition such as active alcohol or other substance abuse or addiction that, in the opinion of the investigator, predisposes the subject to high risk of noncompliance with the protocol.
- Refractory congestive heart failure unresponsive to medical treatment, active infection resistant to all antibiotics, or advanced non-MDS associated pulmonary disease requiring >2 liters per minute oxygen.
- Life expectancy of less than one month
- subjects with TP53 mutations
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): NCT02907359
|Study Director:||Harold Keer, MD, PhD||Astex Pharmaceuticals, Inc.|
|Responsible Party:||Astex Pharmaceuticals, Inc.|
|Other Study ID Numbers:||
|First Posted:||September 20, 2016 Key Record Dates|
|Last Update Posted:||September 5, 2021|
|Last Verified:||September 2021|
|Individual Participant Data (IPD) Sharing Statement:|
|Plan to Share IPD:||No|
Leukemia, Myelomonocytic, Chronic
Neoplasms by Histologic Type
Bone Marrow Diseases