A clinical trial to compare guadecitabine (SGI-110) to other available therapies in patients with myelodysplastic syndromes (MDS) or chronic myelomonocytic leukemia (CMML) who have previously been treated with hypomethylating agents
- Conditions
- Myelodysplastic syndromes (MDS) Chronic myelomonocytic leukemia (CMML)MedDRA version: 20.0 Level: HLT Classification code 10028536 Term: Myelodysplastic syndromes System Organ Class: 100000004851MedDRA version: 21.0 Level: PT Classification code 10009018 Term: Chronic myelomonocytic leukaemia System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2015-005257-12-SE
- Lead Sponsor
- Astex Pharmaceuticals, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- Not specified
- Target Recruitment
- 408
1. 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.
2. Cytologically or histologically confirmed diagnosis of MDS or CMML according to the 2008 World Health Organization (WHO) classification.
3. Performance status (Eastern Cooperative Oncology Group [ECOG]) of 0-2.
4. Subjects with 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, relapsed or was refractory to HMA treatment as follows:
a. Subject received HMA for at least 6 cycles and is transfusion dependent (as defined in 5b below), OR
b. Subject received HMA for at least 2 complete cycles and had disease progression defined as
i. =50% increase in bone marrow blasts from pre-HMA-treatment levels or from nadir post-HMA-treatment levels to >5% (fro subjects with pretreatment or nadir blasts =5%), or to >10% (for subjects with pretreatment or nadir blasts >5%) and/or
ii. Transfusion dependent and =2 g/dL reduction of Hgb from pre-HMA-treatment levels.
In addition to HMAs, other prior treatments for MDS such as lenalidomide, cytarabine, intensive chemotherapy, hydroxyurea, erythropoietin and other growth factors, or hematopoietic cell transplant (HCT) are allowed.
5. Subjects must have either:
a. Bone marrow blasts >5% at randomization, OR
b. 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.
6. 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).
7. 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 (a) while receiving treatment with guadecitabine and for at least 3 months after completing treatment and (b) while receiving treatment with LDAC or IC and for at least 6 months after completing treatment or for the duration specified in local prescribing information, whichever is longer.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 32
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 127
1. Subjects who have been diagnosed as having acute myeloid leukemia (AML) with peripheral blood or bone marrow blasts of =20%.
2. 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.
3. Prior treatment with guadecitabine.
4. Hypersensitivity to decitabine, guadecitabine, or any of their excipients.
5. Second malignancy currently requiring active therapy, except breast or prostate cancer stable on or responding to endocrine therapy.
6. Treated with any investigational drug within 2 weeks of the first dose of study treatment.
7. 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.
8. Known active human immunodeficiency virus (HIV), hepatitis B virus (HBV), or hepatitis C virus (HCV) infection. Inactive hepatitis carrier status or low viral hepatitis titer on antivirals is allowed.
9. 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.
10. 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 (LPM) oxygen.
11. Life expectancy of less than one month
12. Subjects with TP53 mutations.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method