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A Study of Tolinapant in Combination with Oral Decitabine/Cedazuridine and Oral Decitabine/Cedazuridine Alone in Subjects with R/R PTCL
EU CTIS ID: 2022-500391-62-00
What this study is testing
Phase 1: To assess safety, and to identify the recommended phase 2 dose (RP2D) of tolinapant in combination with oral decitabine/cedazuridine. Phase 2: To assess efficacy as determined by overall response rate (ORR)
- Phase I and Phase II (Integrated)- Other
A plain-language read of the study's public EU CTIS listing. The study team confirms the details.
Who can take part
You may be able to join if
- 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.
You likely can't join if
- 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.
See the full eligibility criteria
Who can join
- 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 before study entry is not allowed. e. Creatinine clearance ≥50 mL/min as estimated by Cockcroft-Gault formula. f. Amylase and lipase ≤1.2×ULN.
What rules you out
- 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 must be stabilized and resolved to Grade ≤2.
- Monoclonal antibody treatment for rheumatologic conditions within 4 weeks of study drug initiation
- History of confirmed drug-induced myocarditis or clinically significant myocarditis or documented noninfectious pneumonitis/interstitial lung disease.
- History of Stevens-Johnson syndrome or toxic epidermal necrolysis.
- Concurrent second malignancy currently requiring active therapy, except breast or prostate cancer stable on or responding to endocrine therapy or superficial bladder cancer.
- Any concurrent second malignancy that is metastatic.
- Known central nervous system (CNS) lymphoma.
- Patients with a history of allogeneic transplant are excluded from this study.
- Autotransplant within 100 days of the first dose of the study drug(s).
- Systemic corticosteroids >10mg prednisone equivalent within 7 days of the first dose of study drug(s).
- Anti-T-cell directed therapy: a.Lymphotoxic agents (eg, anti-CD52) in the past 12 months. b.Inhibitory drugs (eg, calcineurin inhibitors) within 4 weeks of the first dose of study drug(s).
The study team makes the final eligibility decision.
Where it's taking place
- United States
- United Kingdom
- Australia
Questions & answers
Do participants get paid in this trial?
This listing doesn't specify compensation. Many trials still reimburse travel or offer a stipend, so it's worth asking the study team when you connect.
Is it free to join, and do I need insurance?
Searching and applying through BridgeMD is free. In clinical trials the study-related treatment and visits are generally provided at no cost to you. You usually don't need insurance to take part - confirm specifics with the study team.
How long does this study last?
The listing doesn't state an exact length. The study team walks you through the schedule and number of visits before you decide to enroll.
Who can join this trial?
This study is enrolling all sexes, 18-64 years, 65+ years. The study team makes the final eligibility decision.
Where is this trial taking place?
Study sites include United States; United Kingdom; Australia. Enter your location above to see the nearest site and check your eligibility.
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BridgeMD is an information and trial-matching tool - not medical advice, and not the study sponsor. Details come from EU CTIS; the study team decides eligibility.