A Phase 3,Multicenter, Randomized, Open Label Study to Compare the Efficacy and Safety of Golcadomide in Combination with Rituximab(Golca + R) Vs Investigator’s Choice in Participants withRelapsed/Refractory Follicular Lymphoma (GOLSEEK-4)

Celgene Corporation5 个研究点分布在 1 个国家目标入组 400 人开始时间: 2026年5月1日最近更新: 2026年2月3日

试验速览

阶段: 3 期
状态: 尚未招募
发起方: Celgene Corporation
入组人数: 400
试验地点: 5
主要终点: Progression-free survival (PFS) per IRAC is

研究概览研究设计入排标准结局指标研究者研究点记录与标识符相似试验

研究概览

简要总结

Follicular lymphoma (FL) is the most common subtype of indolent non-Hodgkin lymphoma

(NHL) in the United States (US) and Western Europe, accounting for approximately 70% of

indolent NHL, and is the second most common type of NHL, accounting for about 20% of all

NHL cases. The incidence of FL in the US was 2.6cases per 100,000 persons per year based on

2015-2019 cases, age-adjusted, with a death rate of 0.4 casesper 100,000 persons per year.

For patients with relapsed/refractory (R/R)FL after at least 1 prior line of therapy, the most

common approach includes immunotherapy, targeted therapiescombinations such as

lenalidomide with rituximab (R-Lenalidomide) and non-crossed resistant chemoimmunotherapy.

Despite the high initial response rates, these therapies are not curative in the long term, leading

to eventual relapse and requiring subsequenttreatment for disease control.

Recently,T-cell directed therapies such as CAR T-cells and bispecific antibodies, have gained

accelerated/conditional regulatory approval in 3L+ FL based on single arm studies showing

improvement in objective or complete response rates above what would be expected from

historical controls. Despite this, the impact of these therapies on patient’s survival remains

unclear. Additionally, tolerability concerns and logistical challenges associated with these

therapies result in many patients not being able to receive them.

Consequently, there remains an unmet need for the development of highly efficacious and well-tolerated regimens that improve outcomes in patients with R/R FL who have received 1or more

prior lines of systemic therapy.

研究设计

研究类型: Interventional
分配方式: Randomized
盲法: None

入排标准

年龄范围: 18.00 Year(s) 至 99.00 Year(s)（—）
性别: All

入选标准

•Signed Written Informed Consent 1) Participants must have signed and dated an IRB or IEC approved written ICF in accordance with regulatory, local, and institutional guidelines. This ICF must be obtained before performing any protocol-related procedures that are not part of normal patient care. Type of Participant and Target Disease Characteristics 2) Participant has histologically confirmed FL (Grade 1, 2, or 3a) as assessed by local pathology. Adequate fresh tumor biopsy tissue or archived tumor biopsy (preferably from the latest relapse if available) with corresponding pathology report for retrospective central pathology confirmation of relapse, is required. Evaluation from fine needle aspirate is not permitted. a) Participant must meet criteria based on investigator assessment to receive systemic therapy. b) Participant must have relapsed or refractory disease, as assessed by the investigator and defined below i) Relapsed FL is defined as relapse after an initial response of CR or PR to the most recent prior therapy. ii) Refractory FL is defined as best response of SD or progressive disease to the most recent prior therapy. 3) Participant has Eastern Cooperative Oncology Group (ECOG) performance status (PS) of lesser than or equal to 2, ECOG PS 3 is allowed if it is lymphoma-related and not due to comorbidities. 4) Participant must have positron emission tomography (PET)-positive disease with at least one PET-positive lesion and measurable disease on cross section imaging by CT, as defined by the Lugano Classification. 5) Participant has received at least 1 or more prior lines of systemic therapy with one line consisting of a combination including an anti-CD20 monoclonal antibody (eg, rituximab, obinutuzumab) and an alkylating agent (eg, cyclophosphamide, bendamustine). Prior treatment with radiation therapy does not count as a line of therapy for eligibility. 6) Participants with an indication for anti-lymphoma treatment as per investigator assessment based on one of the following criteria(modified GELF criteria), but not limited to: a) Bulky disease defined as a nodal or extra nodal (except spleen) mass greater than 7 cm in its greater diameter or, involvement of at least 3 nodal or extra nodal sites (each with a diameter greater than greater than 3 cm) b) Presence of at least one of the following B symptoms i) Fever (greater than 38°C) of unclear etiology ii) Night sweats iii) Weight loss greater than 10 percent within the prior months c) Splenomegaly with inferior margin below the umbilical line d) Any one of the following cytopenia due to lymphoma: i) Platelets less than 100,000 cells per mm3 (100 into 109perL) ii) Absolute neutrophil count (ANC) less than 1,000 cells per mm3 (1.0 into 109per L) iii) Hemoglobin less than 10gperdL (6.25 mmolperL) e) Pleural or peritoneal serous effusion (irrespective of cell content) f) Any compressive syndrome (for example but not restricted to ureteral, orbital, gastrointestinal) 7) Participant must have the following laboratory values: a) Absolute neutrophil count greater than or equal to 1,000 cells/mm3 (1.0 into 109 perL) or greater than or equal 0.5 into 109 perL in case of documented bone marrow involvement by lymphoma or hypersplenism secondary from spleen involvement by lymphoma, without growth factor support for 7 days (14 days if pegylated growth factor is used). b) Platelet count greater than or equal 75,000 cells permm3 (75 into 109 perL) unless greater than or equal 50,000 cells per mm3 (50 into 109 perL) secondary to documented bone marrow involvement by lymphoma or hypersplenism secondary from spleen involvement by lymphoma, without transfusions for 7 days. c) Hemoglobin greater than or equal 7.5 g perdL. 8) Estimated Glomerular function (eGFR) of 7) Participant must have the following laboratory values: a) Absolute neutrophil count greater than or equal to 1,000 cells per mm3 (1.0 into 109 perL) or greater than or equal 0.5 into 109per L in case of documented bone marrow involvement by lymphoma or hypersplenism secondary from spleen involvement by lymphoma, without growth factor support for 7 days (14 days if pegylated growth factor is used). b) Platelet count greater than or equal 75,000 cells per mm3 (75 into 109 perL) unless greater than or equal 50,000 cellspermm3 (50 into 109 perL) secondary to documented bone marrow involvement by lymphoma or hypersplenism secondary from spleen involvement by lymphoma, without transfusions for 7 days. c) Hemoglobin greater than or equal 7.5 gperdL. 30 mLper min per1.73m2 using the modification of diet in renal disease (MDRD) formula (refer to APPENDIX 13) or Chronic Kidney Disease.
•Epidemiology Collaboration formula (CKD-EPI). The same eGFR cutoff applies in case of documented renal involvement by lymphoma. d) Serum aspartate transaminase (AST or SGOT) or alanine transaminase (ALT or SGPT) less than or equal to 2.5 into upper limit of normal (ULN). In case of documented liver involvement by lymphoma, ALT or SGPT and AST or SGOT must be less than or equal 5.0 into ULN. e) Serum total bilirubin less than or equal 1.5 into ULN (corresponding to mild dysfunction as per National Cancer Institute Organ Dysfunction Working Group NCI ODWG criteria). In case of documented liver involvement by lymphoma, serum total bilirubin must be less than or equal to 3.0 into ULN (corresponding to moderate dysfunction as per NCI ODWG criteria). For cases of Gilberts syndrome, serum total bilirubin less than or equal 5.0 into ULN. 9) Adequate cardiac function for participants receiving anthracycline based chemotherapy, defined as left ventricular ejection fraction (LVEF) greater than or equal to 40 percent as assessed by echocardiogram (ECHO) as standard of care or multi-gated acquisition scan (MUGA) if ECHO is not conclusive. 10) Participant is willing to receive thromboembolic medications if deemed high risk for thromboembolic events. 11) Participant is able to understand and voluntarily sign an ICF prior to any study-related assessments or procedures being conducted. 12) Participant is willing and able to adhere to the study visit schedule and all other protocol requirements. 13) Participant agrees to refrain from donating blood while on study intervention, during dose interruptions, and for at least 28 days following the last dose of study intervention. Age of Participant 14) Participant must beat least 18 years of age, inclusive, at the time of signing the ICF. Reproductive Status Note: The investigator or designee shall counsel IOCBP participants (as defined in APPENDIX 3 and APPENDIX 4) and male (as assigned at birth) participants who are sexually active with IOCBP on the importance of pregnancy prevention, the implications of an unexpected pregnancy, and the potential of fetal toxicity occurring due to transmission of study intervention present in seminal fluid to a developing fetus, even if the participant has undergone a successful vasectomy or if the partner is pregnant. Note: The investigator or designee shall evaluate the effectiveness of the contraceptive method in relationship to the first dose of study intervention. Note: Local laws and regulations may require the use of alternative and/or additional contraceptive methods. Note: The investigator is responsible for review of medical history, menstrual history, and recent sexual activity to potentially decrease the risk for inclusion of an individual with an undetected pregnancy. 15) Female (as assigned at birth) participants must adhere to Pregnancy Prevention Plan requirements (See APPENDIX 3 and APPENDIX 4), including: a) Female (as assigned at birth) participants who are not of childbearing potential (as defined in APPENDIX 3 and APPENDIX 4) must have documented proof. Documentation can be obtained from the site personnel’s review of the participant’s medical records, medical examination, or medical history interview. b) Individuals who are not of childbearing potential are exempt (See APPENDIX 3 and APPENDIX 4) from contraceptive requirements. c) IOCBP must have 2 negative pregnancy tests (minimum sensitivity 25 mIU per mL or equivalent units of human chorionic gonadotropin) as verified by the investigator prior to starting golcadomide i) A negative serum pregnancy test (sensitivity of at least 25 mIU per mL) at screening (between 10 to 14 days prior to C1D1). ii) A negative serum or urine pregnancy test (Investigators discretion) within 24 hours prior to Cycle 1 Day 1 of study treatment. Note the screening serum pregnancy test can be used as the test prior to Day 1 study treatment if it is performed within the prior 24 hours. d) Either commit to true abstinence from heterosexual contact (which must be reviewed on a monthly basis and source documented) or agree to use, and be able to comply with two forms of contraception one highly effective, and one additional effective (barrier) measure of contraception without interruption 28 days prior to starting IP, during the study treatment (including dose interruptions), and for at least 28 days after the last dose of golcadomide and according to the approved product/prescribing information for components of chemotherapy regimens, rituximab and lenalidomide, as applicable, whichever is longer. Agree to be counseled about pregnancy precautions and risk of fetal exposure. 16) IOCBP (assigned females at birth) must agree to abstain from breastfeeding during study participation and for at least 28 days after golcadomide discontinuation and according to the approved product or prescribing information for components of chemotherapy regimens, rituximab and lenalidomide. a) Agree to ongoing pregnancy testing during the course of the study, and after the end of study intervention. This applies even if the participant practices true abstinence from heterosexual contact. b) IOCBP and male (as assigned at birth) participants who are sexually active with IOCBP must agree to follow instructions for method(s) of contraception as described in Pregnancy Prevention Plan for golcadomide and included in the ICF. i) Avoid conceiving for up to 28 days after the last dose of golcadomide. ii) Agree to refrain from donating ova while on golcadomide for at least 28 days after its discontinuation. c) Male (as assigned at birth) participants must adhere to Pregnancy Prevention Plan requirements (See APPENDIX 3 and APPENDIX 4) i) Practice true abstinence (which must be reviewed monthly, and source documented) or agree to use a condom during sexual contact with a pregnant female or an FCBP while participating in the study, during dose interruptions and for at least 28 days for golcadomide, and according to the approved product/prescribing information for components of chemotherapy regimens, rituximab and lenalidomide, as applicable, whichever is longer, even if he has undergone a successful vasectomy. ii) Must agree to refrain from donating sperm while on study intervention, during dose interruptions, and for at least 28 days after the last dose of golcadomide or according to the approved product/prescribing information for components of chemotherapy regimens, rituximab and lenalidomide, as applicable, whichever is longer. iii) Agree to be counseled about pregnancy precautions and risk of fetal exposure. iv) IOCBP partners of male participants should be advised to use a highly effective method of contraception during the intervention period and for at least 28 days after the last dose of golcadomide or according to the approved product/prescribing information for components of chemotherapy regimens, rituximab and lenalidomide, as applicable, for the male participant. v) Male participants with a pregnant or breastfeeding partner must agree to remain abstinent from sexual activity or use a male condom during any sexual activity (eg, vaginal, anal, oral), even if the participant has undergone a successful vasectomy, during the intervention period and for at least 28 days after the last dose of golcadomide or according to the approved product/prescribing information for components of chemotherapy regimens, rituximab and lenalidomide, as applicable. vi) Breastfeeding partners of male participants should be advised to consult their health care provider about using appropriate highly effective contraception during the time the male participant is required to use condoms.

排除标准

•Medical Conditions 1) Evidence or history of composite DLBCL and FL or of transformed NHL or any other indolent lymphoma.
•Follicular large cell as per 5th World Health Organization (WHO) sub-classification (grade 3b FL per WHO 4th classification) or duodenal type FL.
•Participant has any significant medical condition, laboratory abnormality, or psychiatric illness that would prevent the participant from compliantly participating in the study based on Investigator’s judgment.
•Participant has any condition that confounds the ability to interpret data from the study based on Investigator’s or Sponsor’s judgment.
•Presence or history of central nervous system (CNS) involvement by lymphoma.
•History of stroke or intracranial hemorrhage within 6 months prior to enrollment.
•Deep venous thrombosis or Pulmonary embolism within 1 month prior to enrollment.
•Participant has any other subtype of lymphoma.
•Participant has persistent diarrhea or malabsorption greater than or equal to Grade 2 (NCI CTCAE v5.0), despite medical management.
•History of another primary malignancy that has not been in remission for greater than or equal to 3 years except for the following non-invasive malignancies: a) Basal cell carcinoma of the skin.
•b) Squamous cell carcinoma of the skin.
•c) Carcinoma in situ of the cervix.
•e) Incidental histologic finding of prostate cancer (T1a or T1b using the TNM tumor nodes, metastasis clinical staging system) or prostate cancer that is curative.
•f) Other completely resected Stage 1 solid tumor that have been treated with curative and have a low risk for recurrence as per the treating investigator.
•Reproductive Status 12) Individuals who are breastfeeding 13) Individuals who are pregnant Prior/Concomitant Therapy 14) Inability to comply with restrictions and prohibited treatments as listed in Section 7.7 Concomitant Therapy.
•Participants who are refractory to both chemotherapies as well as lenalidomide, defined as: • SD or progressive disease as best response to CHOP and Bendamustine based immunochemotherapy or a response to CHOP and Bendamustine based immunochemotherapy that lasted less than 6 months AND • SD or progressive disease as best response to lenalidomide based regimen or a response to lenalidomide based regimen that lasted less than 6 months Note Participants previously refractory to lenalidomide andor exposed will not be randomized in the R-Lenalidomide arm participants who are refractory to R-Chemotherapy (both CHOP and Bendamustine) will not be randomized to R-Chemotherapy arm.
•Participant is on chronic systemic immunosuppressive therapy or corticosteroids (prednisone or equivalent not exceeding 10 mg per day within the last 4 weeks is allowed) stable use of inhaled or topical corticosteroids is allowed.
•Participant has current treatment with strong cytochrome P450 3A4or5 (CYP3A4or5) inhibitors or inducers (see corresponding Section 7.7.1).
•The washout period for strong CYP3A4or5 inhibitors or inducers is 7 days or 5 half-lives (whichever is longer) before initiation of golcadomide.
•Co-adminsitration of moderate cytochrome P450 3A4or5 (CYP3A4or5) inhibitors or inducers may be permitted after discussion with Medical Monitor.
•Participant received live attenuated vaccines within 3 months prior to initiation of study intervention or live coronavirus disease 2019 (COVID-19) vaccines within 30 days prior to C1D
•Physical and Laboratory Test Findings 19) Evidence of organ dysfunction or any clinically significant deviation from normal in physical examination, vital signs, ECG, or clinical laboratory determinations beyond what is consistent with the target population or that places the participant at unacceptable risk if he or she were to participate in the study.
•Participant has known seropositivity for or active viral infection with human immunodeficiency virus (HIV).
•Participant has known chronic active hepatitis B (hepatitis B virus surface antigen HBsAg positive andor hepatitis B core antibody anti-HBc positive with viral DNA positive) or chronic active hepatitis C (positive serology requiring treatment and/or with evidence of liver damage) infection.
•Participant had major surgery less than or equal to 4 weeks (except lymph node biopsy) prior to initiation of treatment.
•Allergies and Adverse Drug Reactions 24) History of allergy or hypersensitivity to any component (including excipients) of the study intervention or related compounds.
•Any prior allergy to CHOP or bendamustine.
•Known sensitivity or allergy to murine products.
•Participant has known allergy to thalidomide, pomalidomide, or lenalidomide.
•Prior history of rash due to these drugs, that resolved with medical management, is not an exclusion criterion.
•Other Exclusion Criteria 28) Prisoners or participants who are involuntarily incarcerated.
•(Note Under certain specific circumstances and only in countries where local regulations permit, a person who has been imprisoned while on study may be permitted to continue as a participant.
•Strict conditions apply).