GOLCADOMIDE for Relapsed or refractory peripheral T-cell lymphoma

Inclusion criteria

• {"criterion_text":"- Subject who understood and voluntarily signed and dated an informed consent prior to any study-specific assessments/procedures being conducted\n- Subject is ≥ 18 years of age at the time of signing the informed consent form (ICF)\n- Subject is willing and able to adhere to the study visit schedule and other protocol requirements\n- 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\n- Subject in Relapse/Refractory situation\n- ECOG performance status 0 to 2, or 3 if thought to be related to lymphoma\n- 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\n- Anticipated life expectancy at least 3 months\n- 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\n- only for VENAZA: 13.\tSubject 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: -\tAngioimmunoblastic type (AITL) -\tFollicular T cell type -\tnot otherwise specified (NOS)\n- only for VENAZA: Contraception (supersedes criterion 10 of the Master protocol): •\tFor 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. •\tFor 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.\n- 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\n- Subject covered by a social security system\n- Subject who understands and speaks one of the country official languages unless local regulation authorizes independent translators\n- 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)\n- Only for Golcaza: ECOG performance status 0 to 1 (supersedes criterium 6 of the Master protocol)\n- 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).\n- 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.\n- 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."}

Exclusion criteria

• {"criterion_text":"- 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)\n- 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.\n- Evidence of central nervous system involvement by lymphoma\n- 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)\n- Any significant medical conditions, laboratory abnormality or psychiatric illness likely to interfere with participation in this clinical study (according to the investigator’s decision)\n- Uncontrolled systemic fungal, bacterial, or viral infection\n- 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)\n- 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)\n- 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.\n- 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).\n- 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.\n- Only for Original-y-T: Prior exposure to PI3Kdelta inhibitor\n- Knowing or suspected hypersensitivity to active substance or to any of the excipients\n- Pregnant, planning to become pregnant, or lactating woman\n- Person deprived of his/her liberty by a judicial or administrative decision\n- Only for Original-y-T: Known or suspected allergies, hypersensitivity, or intolerance to Roginolisib or its excipients.\n- Only for Original-y-T: Inability to swallow food or any condition of the upper gastrointestinal tract that precludes administration of oral medications\n- Only for Original-y-T: Subjects with a diagnosis of cutaneous T-cell lymphoma (CTCL)\n- Only Golcaza: Prior exposure to golcadomide\n- Only for Original-y-T: Prior solid organ transplantation\n- Only Golcaza: Evidence of positive HTLV1 serology\n- 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.\n- Only VENAZA: Evidence of positive HTLV1 serology\n- 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.\n- 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)\n- Only VENAZA: Prior exposure to venetoclax\n- Only VENAZA: Refractory to azacitidine\n- 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)\n- Only VENAZA: Received strong CYP3A inhibitors, moderate CYP3A inhibitors, strong CYP3A inducers, moderate CYP3A inducers within 7 days prior to initiation of study treatment\n- Only for Golcaza:Refractory to azacitidine\n- Only VENAZA: Vaccinated with live, attenuated vaccines within 6 months of enrolment\n- Only VENAZA: Known or suspected allergies, hypersensitivity, or intolerance to azaciticine, venetoclax or their excipients\n- Only VENAZA: Any known malabsorption syndrome or disease associated with malabsorption\n- 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)\n- Only Golcaza: Received strong CYP3A inhibitors, moderate CYP3A inhibitors, strong CYP3A inducers, moderate CYP3A inducers within 7 days prior to initiation of study treatment.\n- Only Golcaza: Vaccinated with live, attenuated vaccines within 6 months of enrolment\n- Only Golcaza: Known or suspected allergies, hypersensitivity, or intolerance to azaciticine, golcadomide or its excipients.\n- Only Golcaza: Any known malabsorption syndrome or disease associated with malabsorption."}

Primary endpoints

• {"endpoint_text":"- 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).","definition_or_measurement_approach":"MTD assessed by analysis of dose-limiting toxicities (DLTs) during Phase 1 dose escalation."}
• {"endpoint_text":"- 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.","definition_or_measurement_approach":"mPFS defined as time from first dose of sub-study treatment to earliest of: disease progression, relapse after CR/PR, administration of any additional unplanned anti-lymphoma treatment (excluding specified transplant consolidations), or death. PD and relapse evaluated according to Lugano 2014 criteria (PET-CT–Based Response)."}

Secondary endpoints

• {"endpoint_text":"-\tObjective response rate (ORR)","definition_or_measurement_approach":""}
• {"endpoint_text":"-\tComplete response rate (CRR)","definition_or_measurement_approach":""}
• {"endpoint_text":"-\tClinical benefit rate (CBR)","definition_or_measurement_approach":""}
• {"endpoint_text":"-\tBest Objective response (BOR)","definition_or_measurement_approach":""}
• {"endpoint_text":"-\tProgression free survival (PFS)","definition_or_measurement_approach":""}
• {"endpoint_text":"-\tLymphoma specific survival (LSS)","definition_or_measurement_approach":""}
• {"endpoint_text":"-\tDuration of Response (DoR)","definition_or_measurement_approach":""}
• {"endpoint_text":"-\tTime to next treatment or death (TNT-D)","definition_or_measurement_approach":""}
• {"endpoint_text":"-\tOverall Survival (OS)","definition_or_measurement_approach":""}
• {"endpoint_text":"-\tRate of transplantation following treatment","definition_or_measurement_approach":""}
• {"endpoint_text":"-\tTime to transplantation","definition_or_measurement_approach":""}
• {"endpoint_text":"-\tSafety","definition_or_measurement_approach":""}

France

Earliest CTIS Part Ii Submission Date

23-05-2025

Latest Decision Or Authorization Date

03-12-2025

Processing Time Days

194

Number Of Sites

20

Number Of Participants

80

Primary sponsor

Full Name

LYSARC

Organisation Type

Laboratory/Research/Testing facility

Country Of Registered Address

France

Third parties

• {"country":"France","full_name":"Assistance Publique Hopitaux De Paris","duties_or_roles":"Biological samples (blood and bone marrow aspirate) banking","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"United States","full_name":"Veeva Systems Inc.","duties_or_roles":"Code 7 (role indicated in dossier, specific duty text not provided)","organisation_type":"Non-Pharmaceutical company"}
• {"country":"France","full_name":"Theradis Pharma","duties_or_roles":"Code 14 (role indicated in dossier, specific duty text not provided)","organisation_type":"Pharmaceutical company"}