A Study of Tolinapant in Combination with Oral Decitabine/Cedazuridine and Oral Decitabine/Cedazuridine Alone in Subjects with R/R PTC
- Conditions
- Subjects with relapsed/refractory peripheral T-cell lymphoma (R/R PTCL)MedDRA version: 20.0Level: PTClassification code: 10042971Term: T-cell lymphoma Class: 100000004864Therapeutic area: Diseases [C] - Immune System Diseases [C20]Therapeutic area: Diseases [C] - Neoplasms [C04]Therapeutic area: Diseases [C] - Hemic and Lymphatic Diseases [C15]
- Registration Number
- CTIS2022-500391-62-00
- Lead Sponsor
- Astex Pharmaceuticals Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- All
- Target Recruitment
- 157
Able to understand and comply with the protocol and study procedures, understand the risks involved in the study, and provide legally effective informed consent before any study-specific procedure is performed., Women of childbearing potential (according to recommendations of the Clinical Trial Facilitation Group [CTFG]) must not be pregnant or breastfeeding and must have a negative pregnancy test at screening. Women of childbearing potential must agree to practice 1 highly effective contraceptive measure of birth control (with a failure rate of <1% per year; preferably with low user dependency) during the study and for 6 months after the last dose of study treatment and must agree not to become pregnant for 6 months after completing treatment; men with female partners of childbearing potential must agree to use a condom and advise their partners to practice 1 highly effective contraceptive measure of birth control (user dependent or with low user dependency) during the study and for at least 3 months after completing treatment, and must agree not to father a child while receiving study treatment and for at least 3 months after completing treatment. See Section 10.2.7 for detailed contraceptive guidance., Men or women 18 years of age or older., Expected life expectancy of >12 weeks., Subjects must have histologically confirmed R/R PTCL (local pathology report) as defined by 2016 World Health Organization (WHO) classification. The following subtypes are eligible for the study: a.Extranodal natural killer (NK)/T-cell lymphoma nasal type. b.Enteropathy-associated T-cell lymphoma. c.Monomorphic epitheliotropic intestinal T-cell lymphoma, d.Hepatosplenic T-cell lymphoma. e.Subcutaneous panniculitis-like T cell lymphoma. f.Peripheral T-cell lymphoma not otherwise specified (PTCL-NOS). g.Angioimmunoblastic T cell lymphoma. h.Follicular peripheral T-cell lymphoma. i.Nodal peripheral T-cell with T-follicular helper (THF) phenotype. j.Anaplastic large-cell lymphoma (ALCL)., Subjects must have evidence of progressive disease and must have received at least two prior systemic therapies. Prior therapies encompass both initial and any subsequent systemic therapies, including autologous transplants., Subjects must have measurable disease by contrast-enhanced diagnostic CT (at least 1 nodal lesion >1.5 cm or extranodal lesions >1.0 cm)., Subjects with CD30-positive disease must have received, be ineligible for, or intolerant to brentuximab vedotin, provided that brentuximab vedotin is locally approved and available. If an investigator determines, and the subject agrees through informed discussion and consent, that the subject will have a minimal likelihood of benefiting from brentuximab vedotin, this should be discussed with the medical monitor to confirm eligibility., Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2., Acceptable organ function, as evidenced by the following laboratory data: a.Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =2.0×upper limit of normal (ULN). b.Total serum bilirubin =1.5×ULN. If a subject has a documented preexisting diagnosis of true Gilbert’s syndrome, AST and ALT must be normal, and total serum bilirubin must be =2.5×ULN. c.Absolute neutrophil count (ANC) =1000 cells/mm3 (=750 cells/mm3 for subjects with lymphoma in bone marrow). d.Platelet count =50,000 cells/mm3 (=25,000 cells/mm3 for subjects with lymphoma in bone marrow). Transfusion within 21 days bef
Prior treatment with tolinapant or any hypomethylating agent., Use of a concomitant medication which is a moderate or strong CYP3A4 inhibitor/inducer within 2 weeks of the start of the study., Use of any vaccine within 10 days of the first dose of the study drug(s)., Hypersensitivity to tolinapant or oral decitabine/cedazuridine, excipients of the drug product, or other components of the study treatment regimen., Poor medical risk because of systemic diseases (eg, uncontrolled infections) in addition to the qualifying disease under study., Life-threatening illness, significant organ system dysfunction, or other condition that,in the investigator’s opinion, could compromise subject safety or the integrity of the study outcomes, or interfere with the absorption or metabolism of tolinapant., A history of, or at risk for, cardiac disease, as evidenced by 1 or more of the following conditions: a. Abnormal left ventricular ejection fraction (LVEF) of <50% on echocardiogram (ECHO) or multiple-gated acquisition scan (MUGA) .b. Congestive cardiac failure of Grade =3 severity according to New York Heart Association (NYHA) functional classification defined as subjects with marked limitation of activity and who are comfortable only at rest. c. Unstable cardiac disease including unstable angina or hypertension as defined by the need for overnight hospital admission within the last 90 days before screening. d. History or presence of complete left bundle branch block, third-degree heart block, cardiac pacemaker, or clinically significant arrhythmia. e. History of long QTc syndrome or ventricular arrhythmias including ventricular bigeminy. f. Screening 12-lead electrocardiogram (ECG) with measurable QTc interval of =470 msec (according to either Fridericia’s or Bazett’s correction). g. Any other condition that, in the opinion of the investigator, could put the subject at increased cardiac risk., Known history of human immunodeficiency virus (HIV) infection; or seropositive results consistent with active hepatitis B virus (HBV) or active hepatitis C virus (HCV) infection., Grade 3 or greater neuropathy., Known significant mental illness or other conditions such as active alcohol or other substance abuse that, in the opinion of the investigator, predisposes the subject to high risk of noncompliance with the protocol treatment or assessments., Prior anticancer treatments or therapies within the indicated time windowbefore first dose of study treatment (tolinapant), as follows:a.Cytotoxic chemotherapy or radiotherapy within 4 weeks prior. Palliative radiotherapy to a single lesion within 2 weeks prior. Any encountered treatment-related toxicities (excepting alopecia) must be stabilized or resolved to Grade 2 or less.b.Monoclonal antibodies within 4 weeks prior. Any encountered treatment-related toxicities must be stabilized or resolved to Grade 2 or less.c.At least 12 weeks must have elapsed since chimeric antigen receptor T-cell (CAR-T) infusion and subjects must have experienced disease progression, and not have residual circulating CAR-T cells in peripheral blood (based on local assessment). Any encountered treatment-related toxicities must have resolved to Grade =1.d.Small molecules or biologics (investigational or approved) within the longer of 3 weeks or 5 half-lives before study treatment. Any encountered treatment-related toxicities mu
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