A Phase 2 Global Study conducted to see the benefit and safety of CC-486 in patients with Myelodysplastic Syndromes who Did Not Respond to Treatment With Azacitidine for injection or Decitabine.
- Conditions
- Myelodysplastic syndrome (MDS)MedDRA version: 18.0Level: LLTClassification code 10068361Term: MDSSystem Organ Class: 100000004864Therapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]
- Registration Number
- EUCTR2014-002675-29-FR
- Lead Sponsor
- Celgene Corporation
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 68
1. Male or female, = 18 years of age at the time of signing the informed consent document.
2. Documented diagnosis of myelodysplastic syndromes (MDS), classified according to French-American British (FAB) cooperation group classification criteria.
3. Adequate course of treatment with an injectable hypomethylating agent (azacitidine for injection or decitabine) as the last therapeutic intervention for myelodysplastic syndromes prior to beginning screening for this study.
4. Documented disease progression or stable disease as best response to treatment (or attempted treatment) with azacitidine for injection or decitabine.
5. Have the last dose of the prior treatment regimen (injectable hypomethylating agent (HMA) – azacitidine for injection or decitabine) not more than 12 weeks prior to screening for this study.
6. No less than 3 weeks between the last dose of the prior treatment regimen (injectable HMA – azacitidine for injection or decitabine) and the planned date of first dose of investigative product.
7. Have an Eastern Oncology Cooperative Group (ECOG) performance status of 0, 1, or 2.
8. Females of childbearing potential may participate, providing they meet the following conditions:
- Agree to use at least two effective contraceptive methods; and
- Have a negative serum pregnancy test at screening; and
- Have a negative serum or urine pregnancy test within 72 hours prior to starting treatment with investigative product and before beginning each subsequent cycle of treatment.
9. Male subjects with a female partner of childbearing potential must agree to use at least two physician-approved contraceptive methods throughout the course of the study and should avoid fathering a child during the course of the study and for 3 months following the last dose of investigational product.
10. Understand and voluntarily sign an informed consent document prior to any study related assessments or procedures are conducted.
11. Be able to adhere to the study visit schedule and other protocol requirements.
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 17
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 51
1. Rapidly-progressing myelodysplastic syndromes (MDS)
2. Acute myelogenous leukemia (AML) – French-American British (FAB) cooperation group classification: = 30% blasts in bone marrow). Subjects known to have = 30% blasts are not eligible for inclusion in this study. Recognizing limitations of blast cell quantification, this protocol will allow subjects with pre-enrollment (screening/baseline) bone marrow blast counts up to 33% to be considered for inclusion.
3. Prior allogeneic or autologous stem cell transplant.
4. Prior exposure to the investigational oral formulation of decitabine.
5. Prior or ongoing response (International Working Group 2006 Hematologic Improvements (HI), Partial Response (PR), Complete Response (CR), or marrow Complete Responses) to treatment with azacitidine for injection or decitabine, including relapsed disease.
6. Ongoing medically significant adverse events from previous treatment, regardless of the time period.
7. Use of any of the following within 28 days prior to the first dose of investigational product:
- thrombopoiesis-stimulating agents ([TSAs]; e.g., Romiplostim, Eltrombopag, Interleukin-11)
- Erythropoietin stimulating agents (ESAs) and other red blood cell hematopoietic growth factors (e.g., Interleukin-3)
- hydroxyurea
8. Concurrent use of corticosteroids unless the subject is on a stable or decreasing dose for = 1 week prior to enrollment for medical conditions other than myelodysplastic syndromes (MDS)
9. History of inflammatory bowel disease (e.g., Crohn’s disease, ulcerative colitis), celiac disease (i.e., sprue), prior gastrectomy or upper bowel removal, or any other gastrointestinal disorder or defect that would interfere with the absorption, distribution, metabolism or excretion of the investigational product and/or predispose the subject to an increased risk of gastrointestinal toxicity.
10. Prior history of malignancies, other than myelodysplastic syndromes, unless the subject has been free of the disease for = 3 years. However, subjects with the following history/concurrent conditions are allowed:
- Basal or squamous cell carcinoma of the skin
- Carcinoma in situ of the cervix
- Carcinoma in situ of the breast
- Incidental histologic finding of prostate cancer (T1a or T1b using the tumor, nodes, metastasis [TNM] clinical staging system)
11. Significant active cardiac disease within the previous 6 months
12. Uncontrolled systemic fungal, bacterial, or viral infection (defined as ongoing signs/symptoms related to the infection without improvement despite appropriate antibiotics, antiviral therapy, and/or other treatment)
13. Known Human Immunodeficiency Virus (HIV) or Hepatitis C (HCV) infection, or evidence of active Hepatitis B Virus (HBV) infection
14. Any of the following laboratory abnormalities:
- Serum aspartate transaminase (AST)/serum glutamic oxaloacetic transaminase (SGOT) or alanine transaminase (ALT)/serum glutamic pyruvate transaminase (SGPT) > 2.5 x upper limit of normal (ULN)
- Serum total bilirubin > 1.5 x upper limit of normal (ULN). Higher levels are acceptable if these can be attributed to active red blood cell precursor destruction within the bone marrow (i.e., ineffective erythropoiesis). Subjects are excluded if there is evidence of autoimmune hemolytic anemia manifested as a corrected reticulocyte count of > 2% with either a positive Coombs’ test or over 50% of indirect bilirubin
- Serum creatinine > 2.5 x upper limit of normal (ULN)
- A
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: The primary objective of this study is to investigate the efficacy of CC-486 in subjects with MDS that did not respond to prior treatment with an injectable hypomethylating agent (HMA –azacitidine for injection or decitabine), or who were unable to tolerate treatment with an injectable HMA.;Secondary Objective: - To assess the safety and tolerability of CC-486 as treatment for MDS<br>- To describe the clinical relevance of objective hematologic and/or biologic responses associated with treatment with CC-486;Primary end point(s): - Overall rate of objective response (ORR) to treatment with CC-486<br>;Timepoint(s) of evaluation of this end point: - Evaluated following Cycles 2, 4, 6 and every 3 cycles thereafter, as well as upon treatment discontinuation.
- Secondary Outcome Measures
Name Time Method