A phase II study evaluating the efficacy and safety of IMetelstat in Patients with HR myElodysplastic SyndromeS or AML failing HMA-based therapy.
- Conditions
- AML and MDS patients failing or being refractory to hypomethylating agent (HMA)-based treatmentTherapeutic area: Diseases [C] - Hemic and Lymphatic Diseases [C15]Therapeutic area: Diseases [C] - Neoplasms [C04]
- Registration Number
- CTIS2022-500721-32-00
- Lead Sponsor
- Gcp-Service International West GmbH
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 46
Signed written informed consent, ECOG performance status of 0-2, Biochemical laboratory test values must be within the following limits: a. AST, ALT and ALP =2.5 times the upper limit of normal (x ULN) b. Serum creatinine =2.0 x ULN c. Total bilirubin =3 x ULN and direct bilirubin =2 x ULN (unless due to Gilbert’s syndrome, ineffective erythropoiesis due to MDS, or hemolysis due to RBC transfusion), Availability of blood counts and transfusion events for previous 16 weeks, Women of childbearing potential and practicing a highly effective method of birth control according to the Clinical Trial Facilitation Coordination Group Recommendation (Version 1.1, 2020)28: - combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation: o oral o intravaginal o transdermal - progestogen-only hormonal contraception associated with inhibition of ovulation: o oral o injectable o implantable - intrauterine device (IUD) - intrauterine hormone-releasing system ( IUS) - bilateral tubal occlusion - vasectomised partner - sexual abstinence For females, these restrictions apply for 3 months after the end of dosing. Note: If the childbearing potential changes after start of the study (e.g., woman who is not heterosexually active becomes active, premenarchal woman experiences menarche) a woman must begin a highly effective method of birth control, as described above, A woman of childbearing potential must have a negative serum (?-human chorionic gonadotropin [?-hCG] pregnancy test at screening and agree to be tested (serum or urine) on day 1 of every cycle and at EOT, A man who is sexually active with a woman of childbearing potential and has not had a vasectomy must agree to use a barrier method of birth control eg, either condom with spermicidal foam/gel/film/cream/suppository or partner with occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository, and all men must also not donate sperm during the study. For males, these restrictions apply for 3 months after the end of dosing, France-specific inclusion criterion: Subjects participating at French sites must be covered by the French public welfare system., Male and female = 18 years at the first screening, Must be able to adhere to the study visit schedule and other protocol requirements, Initial diagnosis of AML or MDS according to WHO 2016 classification, At least one cytopenia (ANC < 1800/µL or platelet count < 100,000/µL or hemoglobin < 10 g/dL), a. Failure to achieve complete or partial response or hematological improvement observed after at least six azacitidine monotherapy or four decitabine monotherapy based 4-week treatment cycles administered during the past two years OR b. Failure to achieve complete or partial response or hematological improvement observed after at least two 4-week treatment cycles with azacitidine plus venetoclax or with decitabine plus venetoclax during the past two years OR c. Relapse after initial complete or partial response or hematological improvement observed after at least six (azacitidine) or four (decitabine) based 4-week treatment cycles administered during the past two years OR d. Relapse after initial complete or partial response or hematological improvement observed after at least two 4-week treatment cycles with azacitidine plus venetoclax or with decitabine plus venetoclax during the past two years OR e. Intolerance to treatment with HMA-based therapy during the past two years,
Chemotherapy within the 14 days prior to the first dose of imetelstat being administered (other than hydroxyurea), Active systemic hepatitis infection requiring treatment (carriers of hepatitis virus are permitted to enter the study), or known acute or chronic liver disease including cirrhosis, Any life-threatening illness, medical condition, or organ system dysfunction which, in the investigator’s opinion, could compromise the subject’s safety, interfere with the imetelstat metabolism, or put the study outcomes at undue risk; Subject has any condition for which, in the opinion of the investigator, participation would not be in the best interest of the subject (eg, compromise the well-being) or that could prevent, limit, or confound the protocol-specified assessments, Females who are pregnant or are currently breastfeeding or planning to become pregnant while enrolled in this study or within 3 months after the end of dosing, Subject is a man who plans to father a child while enrolled in this study or within 3 months after the end of dosing, Subject has known allergies, hypersensitivity, or intolerance to imetelstat or its excipients (refer to the IB), Subject has received an experimental or investigational drug or used an invasive investigational medical device within 30 days prior to day 1 of C1, Prior treatment with imetelstat, Prior history of intensive chemotherapy or hematopoietic stem cell transplant, Major surgery within 4 weeks prior to day 1 of C1 (excluding the placement of vascular access and other minor surgical procedures), Diagnosed or treated for malignancy other than MDS or AML, except: a. Malignancy treated with curative intent and with no known active disease present for 3 years before day 1 of C1 b. Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease c. Adequately treated cervical carcinoma in situ without evidence of disease, Clinically significant cardiovascular disease such as uncontrolled or symptomatic arrhythmias, congestive heart failure, or myocardial infarction within 6 months of day 1 of C1, or any Class 3 (moderate) or Class 4 (severe) cardiac disease as defined by the New York Heart Association Functional Classification, Known history of human immunodeficiency virus (HIV) or any uncontrolled active systemic infection requiring IV antibiotics
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