A Study of Tolinapant in Combination With Oral Decitabine/Cedazuridine and Oral Decitabine/Cedazuridine Alone in Participants With Relapsed/Refractory Peripheral T-cell Lymphoma (R/R PTCL)

Not Recruiting

Trial ID: NCT05403450


The primary purpose of the study is to assess safety, and to identify the recommended phase 2 dose (RP2D) of tolinapant in combination with oral decitabine/cedazuridine in Phase 1 and to assess preliminary efficacy as determined by overall response rate (ORR) in Phase 2.

Official Title

A Phase 1-2, Open-Label Study of the Safety, Pharmacokinetics, Pharmacodynamics, and Preliminary Activity of Tolinapant in Combination With Oral Decitabine/Cedazuridine and Oral Decitabine/Cedazuridine Alone in Subjects With Relapsed/Refractory Peripheral T-cell Lymphoma

Stanford Investigator(s)

Ranjana Advani
Ranjana Advani

Saul A. Rosenberg, MD, Professor of Lymphoma


Inclusion Criteria:

   1. Participants with expected life expectancy of >12 weeks.

   2. Participants 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:

      1. Extranodal natural killer (NK)/T-cell lymphoma nasal type.

      2. Enteropathy-associated T-cell lymphoma.

      3. Monomorphic epitheliotropic intestinal T-cell lymphoma.

      4. Hepatosplenic T-cell lymphoma.

      5. Subcutaneous panniculitis-like T-cell lymphoma.

      6. Peripheral T-cell lymphoma not otherwise specified (PTCL-NOS).

      7. Angioimmunoblastic T-cell lymphoma.

      8. Follicular peripheral T-cell lymphoma.

      9. Nodal peripheral T-cell with T-follicular helper (THF) phenotype.

   10. Anaplastic large-cell lymphoma (ALCL).

   3. Participants must have evidence of progressive disease and must have received at least
   two prior systemic therapies.

   4. Participants must have measurable disease by contrast-enhanced diagnostic CT (at least
   1 nodal lesion >1.5 centimeters (cm) or extranodal lesions >1.0 cm).

   5. Participants with CD30-positive disease must have received, be ineligible for, or
   intolerant to brentuximab vedotin.

   6. Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2.

   7. Acceptable organ function as per protocol.

   8. 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.

Exclusion Criteria:

   1. Prior treatment with tolinapant or any hypomethylating agent.

   2. Hypersensitivity to tolinapant or oral decitabine/cedazuridine, excipients of the drug
   product, or other components of the study treatment regimen.

   3. Poor medical risk because of systemic diseases (e.g., uncontrolled infections) in
   addition to the qualifying disease under study.

   4. Life-threatening illness, significant organ system dysfunction, or other condition
   that, in the investigator's opinion, could compromise participant safety or the
   integrity of the study outcomes, or interfere with the absorption or metabolism of

   5. A history of, or at risk for, cardiac disease, as evidenced by 1 or more of the
   following conditions:

      1. Abnormal left ventricular ejection fraction.

      2. Congestive cardiac failure of Grade ≥3.

      3. Unstable cardiac disease.

      4. History or presence of complete left bundle branch block, third-degree heart
      block, cardiac pacemaker, or clinically significant arrhythmia.

      5. History of long QTc syndrome or ventricular arrhythmias including ventricular

      6. Screening 12-lead electrocardiogram (ECG) with measurable QTc interval of ≥470
      milliseconds (msec) (according to either Fridericia's or Bazett's correction).

      7. Any other condition that, in the opinion of the investigator, could put the
      participant at increased cardiac risk.

   6. Known history of human immunodeficiency virus (HIV) infection; or seropositive results
   consistent with active hepatitis B virus (HBV) or active hepatitis C virus (HCV)

   7. Grade 3 or greater neuropathy.

   8. Known significant mental illness or other conditions such as active alcohol or other
   substance abuse that, in the opinion of the investigator, predisposes the participant
   to high risk of noncompliance with the protocol treatment or assessments.

   9. Prior anticancer treatments or therapies within the indicated time window before first
   dose of study treatment (tolinapant), as follows:

      1. Cytotoxic chemotherapy or radiotherapy within 4 weeks prior.

      2. Monoclonal antibodies within 4 weeks prior.

      3. At least 12 weeks must have elapsed since chimeric antigen receptor T-cell
      (CAR-T) infusion.

      4. Small molecules or biologics (investigational or approved) within the longer of 3
      weeks or 5 half-lives before study treatment.

10. Monoclonal antibody treatment for rheumatologic conditions within 4 weeks of study
   drug initiation.

11. Concurrent second malignancy currently requiring active therapy, except breast or
   prostate cancer stable on or responding to endocrine therapy or superficial bladder

12. Any concurrent second malignancy that is metastatic.

13. Known central nervous system (CNS) lymphoma.

14. Participants with a history of allogeneic transplant are excluded from this study.

15. Autotransplant within 100 days of the first dose of the study drug(s).

16. Systemic corticosteroids >10 mg prednisone equivalent within 7 days of the first dose
   of study drug(s).

17. Anti-T-cell directed therapy:

      1. Lymphotoxic agents (e.g., anti-CD52) in the past 12 months.

      2. Inhibitory drugs (e.g., calcineurin inhibitors) within 4 weeks of the first dose
      of study drug(s).

18. Use of a concomitant medication which is a moderate or strong CYP3A4 inhibitor/inducer
   within 2 weeks of the start of the study.

19. Use of any vaccine within 10 days of the first dose of the study drug(s).


drug: Tolinapant

drug: Decitabine + Cedazuridine

Not Recruiting

Contact Information

Stanford University
School of Medicine
300 Pasteur Drive
Stanford, CA 94305
Daniel Heck

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