A Platform Trial Evaluating New Drugs or Combination in R/R Peripheral T-cell Lymphomas

Phase 1

Not yet recruiting

• Conditions: Peripheral T Cells Lymphoma (PTCL)
• Interventions: Drug: roginolisib; Drug: golcadomide; Drug: azacitidine

• Registration Number: NCT07018752
• Lead Sponsor: The Lymphoma Academic Research Organisation

Brief Summary

This study is a platform trial for the evaluation of new drugs or combination of drugs in relapsed or refractory peripheral T-cell lymphomas.

The objective of the study is to generate exploratory data on new drugs or combination of drugs to treat refractory/relapse peripheral T-cells lymphoma to better identify the population of interest and design future correct clinical trials.

Primary objectives of the different sub-studies :

* phase 1 sub-studies: determine the safety and tolerability of escalating doses of the sub-study treatment

* phase 2 sub-studies: identify drugs that will improve significantly the outcome in target patients Secondary objectives of both sub-studies: analyze the response rate, the clinical benefit rate, the progression-free survival, the duration of response, the time to next treatment or death, the overall survival, the rate of transplantation following study treatment and the safety profile of the drugs used

Detailed Description

This study is a platform trial evaluating new drugs or combination of drugs in relapsed or refractory peripheral T-cell lymphomas via multiple sub-studies. For phase 1 sub-studies, at least 18 evaluable patients are required per each sub-study. For phase 2 sub-studies, 31 evaluable patients are required per sub-study.

Each sub-study has its own specificities:

* Origina-ly-T: open-label phase 2 study evaluating the efficacy and safety of roginolisib in relapsed/refractory peripheral T-cells lymphoma. Study treatment will be administered until unacceptable toxicity, disease progression, subject/physician decision to withdraw, whichever happens first.

* GolcAza: open-label phase 1 study to identify the maximum tolerated dose of golcadomide in association with oral 5-azacitidine and evaluate the efficacy and safety of the determined combination of oral 5-azacitidine and golcadomide in relapsed/refractory follicular helper T-cell lymphoma subjects. Subjects will receive golcadomide and oral 5-azacitidine until end of study or until disease progression, unacceptable toxicity, subject/physician decision to withdraw, whichever occurs first.

Study Timeline

• Status Verified: 2025-06
• Study First Submitted: 2025-06-04
• Study First Submitted QC: 2025-06-04
• Study First Posted: 2025-06-12
• Last Update Submitted: 2025-06-13
• Last Update Posted: 2025-06-17
• Study Start: 2025-08
• Primary Completion: 2028-04
• Study Completion: 2030-01

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 49

Inclusion Criteria

Not provided

Exclusion Criteria

1. Evidence of central nervous system involvement by lymphoma;

2. Any significant medical conditions, laboratory abnormality or psychiatric illness likely to interfere with participation in this clinical study (according to the investigator's decision);

3. Uncontrolled systemic fungal, bacterial, or viral infection;

4. Known Hepatitis C Virus (HCV) or active Hepatitis B Virus (HBV) infection defined as subject with detectable viral load (respectively detectable viral RNA or detectable viral DNA);

5. Active malignancy other than the one treated in this research, unless the subject has been free of the disease for 2 years (subjects with a history of a completely resected non-melanoma skin cancer or successfully treated for an in-situ carcinoma are eligible);

6. Use of any standard or experimental anti-cancer drug therapy within 28 days or a minimum of 5 half-lives of the drug, whatever the shortest prior to first administration of study drug;.

7. Subject taking corticosteroids within 14 days prior to first administration of study drug, unless administered at a cumulated dose equivalent of prednisone ≤ 20mg /day (within these 14 days);

8. Subject with prior autologous hematopoietic cell transplantation (auto-HCT) ≤ 3 months prior to starting investigational product(s). If subject had autologous SCT (Stem Cell Transplant) > 3 months prior to the start of investigational product(s), any unresolved (Grade > 1) autologous SCT-related toxicity;

9. Subject with prior allogeneic hematopoietic cell transplantation (allo-HCT) with either standard or reduced intensity conditioning ≤ 3 months prior to starting investigational product(s). If subject had allogeneic SCT > 3 months prior to the start of investigational product(s) and still has any unresolved situation including (Grade > 1) treatment-related toxicity and/or ongoing immunosuppressor therapy and/or more than mild (NIH consensus) chronic graft-versus-host disease;

10. Subject with major surgery ≤ 14 days prior to starting investigational product(s). Subjects must have recovered from any clinically significant effects of recent surgery;

11. Subject who has received prior localized anticancer therapy (eg. radiotherapy [including palliative radiotherapy]) ≤ 14 days prior to starting investigational product(s);

12. Known or suspected hypersensitivity to active substance or to any of the excipients;

13. Pregnant, planning to become pregnant, or lactating woman;

14. Person deprived of his/her liberty by a judicial or administrative decision;

    Exclusion criteria specific to Origina-ly-T sub-study:

15. Positive HIV test at screening, with the following exception: individuals with a positive HIV test at screening are eligible provided they are stable on antiretroviral therapy for at least 4 weeks, have a CD4 count ≥ 200/uL, have an undetectable viral load, and have not had a history of opportunistic infection attributable to HIV within the last 12 months

16. Impaired renal function (calculated CKP-EPI, MDRD or Cockcroft-Gault Creatinine Clearance < 30 ml/min) or impaired liver function tests (serum total bilirubin level > 34 μmol/L), except in case of Gilbert's Syndrome, or documented liver or pancreatic involvement by lymphoma, serum transaminases (AST or ALT) > 3 upper normal limits, unless elevated to up to 5 x ULN due to peripheral T-cells lymphoma);

17. Significant cardiovascular disease [e.g., Objective Class C or D heart diseases (cf. Classes of Heart Failure | American Heart Association)], myocardial infarction within the previous 6 months, unstable arrhythmia, or unstable angina);

18. Prior exposure to PI3Kdelta inhibitor;

19. Known or suspected allergies, hypersensitivity, or intolerance to Roginolisib or its excipients;

20. Inability to swallow food or any condition of the upper gastrointestinal tract that precludes administration of oral medications;

21. Subjects with a diagnosis of cutaneous T-cell lymphoma (CTCL);

22. Prior solid organ transplantation;

Exclusion criteria specific to GolcAza sub-study:

15. Evidence of positive HTLV1 serology;

16. Positive HIV test at screening, with the following exception: individuals with a positive HIV test at screening are eligible provided they are stable on antiretroviral therapy for at least 4 weeks, have a CD4 count ≥ 200/uL, have an undetectable viral load, and have not had a history of opportunistic infection attributable to HIV within the last 12 months;

17. Impaired renal function (calculated CKD-EPI, MDRD or Cockcroft-Gault Creatinine Clearance < 30 ml/min) or impaired liver function tests (serum total bilirubin level > 34 μmol/L) except in case of Gilbert's Syndrome, or documented liver or pancreatic involvement by lymphoma, serum transaminases (AST or ALT) > 3 upper normal limits (except documented liver involvement by lymphoma);

18. Prior exposure to golcadomide;

19. Refractory to azacitidine;

20. Significant cardiovascular disease [e.g., Objective Class C or D heart diseases (cf. Classes of Heart Failure | American Heart Association)], myocardial infarction ≤ 3 months prior to starting golcadomide, unstable angina pectoris ≤ 3 months prior to starting golcadomide), or complete left bundle branch or bifascicular block), congenital long QT syndrome, QTcF ≥ 470 msec on screening, persistent or clinically meaningful ventricular arrhythmias;

21. Received strong CYP3A inhibitors, moderate CYP3A inhibitors, strong CYP3A inducers, moderate CYP3A inducers within 7 days prior to initiation of study treatment;

22. Vaccinated with live, attenuated vaccines within 6 months of enrollment;

23. Known or suspected allergies, hypersensitivity, or intolerance to azacitidine, golcadomide or its excipients;

24. Any known malabsorption syndrome or disease associated with malabsorption.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Origina-ly-T	roginolisib	Open-label phase 2 sub-study to evaluate the efficacy and safety of roginolisib in relapsed/refractory peripheral T-cells lymphoma. Study treatment will be administered until unacceptable toxicity, disease progression, subject/physician decision to withdraw, whichever happens first. 31 evaluable patients needed.
GolcAza	golcadomide	Open-label phase 1 sub-study to identify the maximum tolerated dose of golcadomide in association with oral 5-azacitidine and evaluate the efficacy and safety of the determined combination of oral 5-azacitidine and golcadomide in relapsed/refractory follicular helper T-cell lymphoma subjects. Subjects will receive golcadomide and oral 5-azacitidine until end of study or until disease progression, unacceptable toxicity, subject/physician decision to withdraw, whichever occurs first. Minimum 18 evaluable patient required.
GolcAza	azacitidine	Open-label phase 1 sub-study to identify the maximum tolerated dose of golcadomide in association with oral 5-azacitidine and evaluate the efficacy and safety of the determined combination of oral 5-azacitidine and golcadomide in relapsed/refractory follicular helper T-cell lymphoma subjects. Subjects will receive golcadomide and oral 5-azacitidine until end of study or until disease progression, unacceptable toxicity, subject/physician decision to withdraw, whichever occurs first. Minimum 18 evaluable patient required.

Primary Outcome Measures

Name	Time	Method
Maximum Tolerated Dose	From enrollment to end of treatment of sub-study GolcAza (= maximum 2 years from enrollment)	MTD
Recommended Phase II Dose	From enrollment to end of treatment of sub-study GolcAza (= maximum 2 years from enrollment)	RP2D
Modified Progression-Free Survival	From enrollment to end of follow-up period of Origina-ly-T (= maximum 2 years after enrollment)	mPFS

Trial Locations

Locations (20)

Institut d'Hématologie de Basse Normandie - Service Hématologie (CHU Hôpital Côte de Nacre); 🇫🇷 Caen, France

CHU Estaing - Service Thérapie Cellulaire et Hématologie Clinique; 🇫🇷 Clermont-Ferrand, France

Hôpital Henri Mondor - Unité Hémopathies Lymphoïdes; 🇫🇷 Créteil, France

CHU Dijon Bourgogne - Service Hématologie Clinique; 🇫🇷 Dijon, France

CHU de Grenoble - Service Hématologie; 🇫🇷 La Tronche, France

CH du Mans - Centre de Cancérologie de la Sarthe - Service Hématologie; 🇫🇷 Le Mans, France

CHU de Lille - Hôpital Claude Huriez - Service des Maladies du Sang; 🇫🇷 Lille, France

Institut Paoli Calmettes - Service Hématologie; 🇫🇷 Marseille, France

CHU de Montpellier - Département d'Hématologie Clinique; 🇫🇷 Montpellier, France

CHU de Nantes - Service Hématologie; 🇫🇷 Nantes, France

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