Platform - a Platform Trial, Evaluating New Drugs or Combination in Relapsed or Refractory Peripheral T-Cell Lymphomas

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Lysarc

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Hemic and Lymphatic Diseases [C15]

Trial duration

20 Aug 2025 → ongoing

Decision date (initial)

2025-06-03

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

iOnctura SA · Bristol Myers Squibb BMS · AbbVie Inc.

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Others

Phase 1: To determine the safety and tolerability of escalating doses of the sub-study treatment in subjects with Relapsed/Refractory (R/R) PTCL by assessing the maximum tolerated dose (MTD) and the recommended phase II dose. Assessment of the MTD will be performed by the analysis of the dose-limiting toxicities (DLTs).
Phase 2: Identifying, based on a platform trial, drugs that will improve significantly outcome in relapsed/refractory (R/R) PTCL subjects. The primary endpoint is Modified Progression-Free Survival (mPFS), defined as time from first dose of sub-study treatment until one of the following events occurs, whichever comes first:
a) Disease progression (PD) b) Relapse after achievement of CR or PR c) Administration of any additional unplanned anti-lymphoma treatment (except allogeneic or autologous hematopoietic cell transplantations used as consolidation treatment) d) Death due to any cause. PD and relapse will be evaluated according to Lugano 2014 criteria (PET-CT–Based Response).

Secondary objectives 12

1. Objective response rate (ORR)
2. Complete response rate (CRR)
3. Clinical benefit rate (CBR)f
4. Best Objective response (BOR)
5. Progression free survival (PFS)
6. Lymphoma specific survival (LSS)
7. Duration of Response (DoR)
8. Time to next treatment or death (TNT-D)
9. Overall Survival (OS)
10. Rate of transplantation following treatment
11. Time to transplantation
12. Safety

Conditions and MedDRA coding

RELAPSED OR REFRACTORY PERIPHERAL T-CELL LYMPHOMAS

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 19

1. Subject who understood and voluntarily signed and dated an informed consent prior to any study-specific assessments/procedures being conducted
2. Contraception: • For women of childbearing potential (WOCBP): must have a negative result for pregnancy test, at screening and within 24 hours prior to initiating study treatment. The WOCP agree to abstain from becoming pregnant or breastfeeding, to remain abstinent (from heterosexual intercourse) or use at least one highly effective method of contraception and to refrain from donating eggs, during the treatment period (including periods of treatment interruption) and for at least the delay described in the sub-protocol for the concerned molecules • For men of reproductive potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use at least a condom as method of contraception with a non-pregnant female partner of childbearing potential or a pregnant female partner, and to refrain from donating sperm, during the treatment period (including periods of treatment interruption), and for at least the delay described in the subprotocol for the concerned molecules
3. Subject covered by a social security system
4. Subject who understands and speaks one of the country official languages unless local regulation authorizes independent translators
5. only for Golcaza: Subject had local diagnosed (nodal) follicular helper T cell lymphoma according to WHO classification 2022 or ICC 2022 classification based on a surgical lymph node biopsy or needle core biopsy including any one of the following type: - Angioimmunoblastic type (AITL) - Follicular T cell type - not otherwise specified (NOS)
6. Only for Golcaza: ECOG performance status 0 to 1 (supersedes criterium 6 of the Master protocol)
7. Only for Golcaza: Subjects must have an International normalized ratio (INR) < 1.5 x ULN and partial thromboplastin time (aPTT) < 1.5 x ULN (for subjects not receiving therapy).
8. Only for Golcaza: Contraception (supersedes criterium 10 of the Master protocol): • For women of childbearing potential (WOCP): must have a negative result for pregnancy test, 10 to 14 days prior to initiating study treatment and within 24 hours prior to initiating study treatment. WOCP agree to abstain from becoming pregnant or breastfeeding and to remain abstinent (refrain from heterosexual intercourse) or use two adequate methods of contraception, including at least one highly effective method of contraception , at least 28 days before the first dose of study treatment , during the treatment period (including periods of treatment interruption), and for at least 28 days after the last dose of golcadomide, and 6 months after the last dose of azacitidine. Women must refrain from donating eggs during this same period. • For men: during the treatment period (including periods of treatment interruption), and for at least 28 days after the last dose of golcadomide and 3 months after the last dose of azacitidine male subjects must: • With female partners of childbearing potential: use a condom associated with a highly effective method of contraception or remain abstinent (refrain from heterosexual intercourse) • With pregnant female partners: use a condom or remain abstinent (refrain from heterosexual intercourse) Men must refrain from donating sperm during this same period.
9. Only for Original-y-T: For Anaplastic large cell lymphoma subjects: failed or ineligible or intolerant to brentuximab vedotin. For Extranodal NK/T-cell lymphoma: failed or ineligible or intolerant to asparaginase-containing regimen.
10. Subject is ≥ 18 years of age at the time of signing the informed consent form (ICF)
11. Subject is willing and able to adhere to the study visit schedule and other protocol requirements
12. Subject with histologically proven peripheral T-cell lymphoma according to the criteria of the WHO classification 2017 or 2022 (subjects with mycosis fungoides, Sezary syndrome, lymphoblastic or large granular lymphocytic lymphoma will be excluded). Tumor tissue (initial diagnosis or relapse) should be available for central pathology review and biological characterization
13. Subject in Relapse/Refractory situation
14. ECOG performance status 0 to 2, or 3 if thought to be related to lymphoma
15. Adequate bone marrow function as defined by: • ANC ≥ 1,5 x 109/L (≥ 1 x 109/L if related to lymphoma) • Platelet ≥ 75 x 109/L (≥ 50 x 109/L if related to lymphoma) • Hemoglobin ≥ 8 g/dL
16. Anticipated life expectancy at least 3 months
17. Presence of disease specific criteria allowing response evaluation. Unless otherwise specified, such criteria include a. Baseline fluorodeoxyglucose PET-scan demonstrating at least one positive (FDG-avid) lesion. b. And at least one bi-dimensionally measurable nodal lesion, defined as > 1.5 cm in its longest dimension, or at least one bidimensionally measurable extra nodal lesion, defined as > 1.0 cm in its longest dimension
18. only for VENAZA: 13. Subject had local diagnosed (nodal) follicular helper T cell lymphoma according to WHO classification 2022 or ICC 2022 classification based on a surgical lymph node biopsy or needle core biopsy including any one of the following type: - Angioimmunoblastic type (AITL) - Follicular T cell type - not otherwise specified (NOS)
19. only for VENAZA: Contraception (supersedes criterion 10 of the Master protocol): • For women of childbearing potential (WOCBP): must have a negative result for pregnancy test, at screening and within 24 hours prior to initiating study treatment. The WOCP agree to abstain from becoming pregnant or breastfeeding, to remain abstinent (from heterosexual intercourse) or use at least one highly effective method of contraception and to refrain from donating eggs, during the treatment period (including periods of treatment interruption) and up to 30 days after the subject’s last dose of venetoclax and 6 months after the last dose of oral 5-azacitidine. If the female subject uses a hormonal contraceptive method (hormonal contraceptive pills or devices) as highly effective birth control method, a barrier method should be add. • For men of reproductive potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use at least a condom as method of contraception with a non-pregnant female partner of childbearing potential or a pregnant female partner (even if the male subject has undergone a successful vasectomy) and to refrain from donating sperm, during the treatment period (including periods of treatment interruption), and up to 30 days after the subject’s last dose of venetoclax and 3 months after the last dose of oral 5-azacitidine.

Exclusion criteria 42

1. Only for Original-y-T: 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 PTCL)
2. Only Golcaza: 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)
3. Only Golcaza: Prior exposure to golcadomide
4. Only for Golcaza:Refractory to azacitidine
5. Only Golcaza: 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.
6. Only Golcaza: Received strong CYP3A inhibitors, moderate CYP3A inhibitors, strong CYP3A inducers, moderate CYP3A inducers within 7 days prior to initiation of study treatment.
7. Only Golcaza: Vaccinated with live, attenuated vaccines within 6 months of enrolment
8. Only Golcaza: Known or suspected allergies, hypersensitivity, or intolerance to azaciticine, golcadomide or its excipients.
9. Only Golcaza: Any known malabsorption syndrome or disease associated with malabsorption.
10. Only for Original-y-T: 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.
11. Evidence of central nervous system involvement by lymphoma
12. Only for Original-y-T: 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)
13. Any significant medical conditions, laboratory abnormality or psychiatric illness likely to interfere with participation in this clinical study (according to the investigator’s decision)
14. Uncontrolled systemic fungal, bacterial, or viral infection
15. 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)
16. 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)
17. 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.
18. 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).
19. Subject with prior autologous hematopoietic cell transplantation (auto-HCT) ≤ 3 months prior to starting investigational product(s). If subject had autologous SCT > 3 months prior to the start of investigational product(s), any unresolved (Grade > 1) autologous SCT-related toxicity.
20. 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.
21. Subject with major surgery ≤ 14 days prior to starting investigational product(s). Subjects must have recovered from any clinically significant effects of recent surgery.
22. Subject who has received prior localized anticancer therapy (eg. radiotherapy [including palliative radiotherapy]) ≤ 14 days prior to starting investigational product(s).
23. Only for Original-y-T: Prior exposure to PI3Kdelta inhibitor
24. Knowing or suspected hypersensitivity to active substance or to any of the excipients
25. Pregnant, planning to become pregnant, or lactating woman
26. Person deprived of his/her liberty by a judicial or administrative decision
27. Only for Original-y-T: Known or suspected allergies, hypersensitivity, or intolerance to Roginolisib or its excipients.
28. Only for Original-y-T: Inability to swallow food or any condition of the upper gastrointestinal tract that precludes administration of oral medications
29. Only for Original-y-T: Subjects with a diagnosis of cutaneous T-cell lymphoma (CTCL)
30. Only for Original-y-T: Prior solid organ transplantation
31. Only Golcaza: Evidence of positive HTLV1 serology
32. Only for Golcaza: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.
33. Only for VENAZA: Evidence of positive HTLV1 serology
34. Only VENAZA: 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.
35. Only VENAZA: 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)
36. Only VENAZA: Prior exposure to venetoclax
37. Only VENAZA: Refractory to azacitidine
38. Only VENAZA: 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)
39. Only VENAZA: Received strong CYP3A inhibitors, moderate CYP3A inhibitors, strong CYP3A inducers, moderate CYP3A inducers within 7 days prior to initiation of study treatment
40. Only VENAZA: Vaccinated with live, attenuated vaccines within 6 months of enrolment
41. Only VENAZA: Known or suspected allergies, hypersensitivity, or intolerance to azaciticine, venetoclax or their excipients
42. Only VENAZA: Any known malabsorption syndrome or disease associated with malabsorption

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Phase 1: maximum tolerated dose (MTD) and the recommended phase II dose. Assessment of the MTD will be performed by the analysis of the dose-limiting toxicities (DLTs).
2. Phase 2: Modified Progression-Free Survival (mPFS), defined as time from first dose of sub-study treatment until one of the following events occurs, whichever comes first: a) Disease progression (PD) b) Relapse after achievement of CR or PR c) Administration of any additional unplanned anti-lymphoma treatment (except allogeneic or autologous hematopoietic cell transplantations used as consolidation treatment) d) Death due to any cause.

Secondary endpoints 12

1. - Objective response rate (ORR)
2. - Complete response rate (CRR)
3. - Clinical benefit rate (CBR)
4. - Best Objective response (BOR)
5. - Progression free survival (PFS)
6. - Lymphoma specific survival (LSS)
7. - Duration of Response (DoR)
8. - Time to next treatment or death (TNT-D)
9. - Overall Survival (OS)
10. - Rate of transplantation following treatment
11. - Time to transplantation
12. - Safety

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 6

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Lysarc

Sponsor organisation

LYSARC

Address

2d Lyon Sud Batiment

City

Pierre Benite Cedex

Postcode

69495

Country

France

Scientific contact point

Organisation

LYSARC

Contact name

François LEMONNIER

Public contact point

Organisation

LYSARC

Contact name

Anne Viola

Third parties 3

Locations

1 EU/EEA country · 20 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 35 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

3 submissions — initial application plus substantial / non-substantial modifications