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RecruitingLast updated: 3 April 2024

This study aims to determine the recommended dose level, safety and effectiveness of an oral drug when it is given in addition to another oral combination treatment in people with relapsed or refractory peripheral T-cell lymphomaA 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

Clinical summary

Summary

This study will assess the safety, and identify the recommended phase 2 dose (RP2D) of an oral drug called Tolinapant when given in addition to the oral combination treatment of decitabine + cedazuridine. It will also assess the preliminary efficacy of this treatment compared to treatment with just decitabine + cedazuridine.

Eligible participants will be randomly allocated into one of two treatment arms. Treatment cycles are 28-days in length.

In Arm A, participants will receive Tolinapant + Oral Decitabine/Cedazuridine. Tolinapant will be given once daily on Days 1 to 7 and 15 to 21 of each treatment cycle, in combination with decitabine/cedazuridine fixed-dose combination tablet, once daily, on days determined by the Lead in Phase. The starting dose of tolinapant will be escalated stepwise in successive cohorts until the RP2D is determined.

Based on the RP2D and results determiend from Phase 1, participants would receive tolinapant at the identified RP2D in combination with decitabine/cedazuridine fixed-dose combination tablet.

In Arm B, participants will receive Oral Decitabine/Cedazuridine. Decitabine/cedazuridine will be given as a fixed-dose combination tablet once daily on days determined by the Lead-in Phase. 

Conditions

This trial is treating patients with peripheral T-cell lymphoma

Cancer

Blood Cancers Haematological

Age

People18+

Phase

I/II

More information

Trial Identifiers

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Trial sponsor

Astex Pharmaceuticals, Inc.

Scientific 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

Eligibility

Inclusion

  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

  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 tolinapant.
  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 bigeminy.
    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) infection.
  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 cancer.
  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).

Inclusion

  • You have had treatment, but your cancer has come back.
  • You have had treatment but your cancer has gotten worse or has not responded to the treatment you have been given.
  • You are able to swallow medication by mouth.

Exclusion

  • You have been diagnosed with a prior or secondary type of cancer.
  • You have certain types of non-cancer medical conditions.
  • You have had certain treatments, surgical procedures or drugs.
Message

Clinical trials have complex eligibility criteria.

Ask your doctor if this trial could be right for you.

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