A Study to Compare the Efficacy and Safety of Golcadomide in Combination With Rituximab (Golca + R) vs Investigator's Choice in Participants With Relapsed/Refractory Follicular Lymphoma Who Have Received at Least 1 Prior Line of Systemic Therapy (GOLSEEK-4)

Официальное название

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 With Relapsed/Refractory Follicular Lymphoma Who Have Received at Least 1 Prior Line of Systemic Therapy

Обзор

The study is designed as a multicenter, randomized, open label Phase 3 study to compare the efficacy and safety of golcadomide in combination with rituximab vs investigator's choice in participants with relapsed/refractory follicular lymphoma who have received at least one line of prior systemic therapy.

Вмешательства

• Препарат Golcadomide
  Specified dose on specified days
• Препарат Rituximab
  Specified dose on specified days
• Препарат Lenalidomide
  Specified dose on specified days
• Препарат Cyclophosphamide
  Specified dose on specified days
• Препарат Doxorubicin
  Specified dose on specified days
• Препарат Vincristine
  Specified dose on specified days
• Препарат Prednisone/Prednisolone
  Specified dose on specified days
• Препарат Bendamustine
  Specified dose on specified days

Первичные конечные точки

• Progression free survival (PFS) assessed by Independent Review Adjudication committee (IRAC) [Срок оценки: Up to approximately 32 Months]

Вторичные конечные точки (12)

• Overall response rate (ORR) assessed by IRAC [Срок оценки: Up to approximately 32 Months]
• Overall survival (OS) [Срок оценки: Up to approximately 83 Months]
• PFS as assessed by investigator [Срок оценки: Up to approximately 32 Months]
• ORR as assessed by investigator [Срок оценки: Up to approximately 32 Months]
• Number of participants who achieve complete metabolic response (CMR) [Срок оценки: Up to approximately 32 Months]
• Duration of Response (DoR) [Срок оценки: Up to approximately 32 Months]
• Event free survival (EFS) [Срок оценки: Up to approximately 32 Months]
• Time to next anti-lymphoma treatment (TTNT) [Срок оценки: Up to approximately 32 Months]
• PFS on next anti-lymphoma treatment (PFS2) [Срок оценки: Up to approximately 32 Months]
• Time from randomization to meaningful improvement in primary domains of interest in the European Organization for Research and Treatment of Cancer - Quality of Life C30 (EORTC QLQ-C30) Questionnaire [Срок оценки: Up to approximately 32 Months]
• Time from randomization to meaningful improvement in primary domains of interest in the European Organization for Research and Treatment of Cancer - Non- Hodgkin Lymphoma- Low Grade- 20 items (EORTC QLQNHL- LG20) Questionnaire [Срок оценки: Up to approximately 32 Months]
• Minimal residual disease (MRD) negativity [Срок оценки: Up to approximately 32 Months]

Критерии участия

Критерии включения

\- Participant has histologically confirmed FL (Grade 1, 2, 3a or classic FL) as assessed by local pathology. Adequate fresh tumor biopsy tissue or archived tumor biopsy 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.

\- Relapsed or refractory disease: 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 PD or a response that lasted less than 6 months to the most recent prior therapy.

• Eastern Cooperative Oncology Group (ECOG) 0-2 (ECOG 3 authorized if it is due to lymphoma and not comorbidities).
• 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 Lugano classification.
• Participants with an indication for anti-lymphoma treatment as per investigator assessment based on modified Groupe d'Etude des Lymphomes Folliculaires (GELF) criteria.
• 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.
• Lab parameters:

i) Absolute neutrophil count (ANC) ≥ 1,000 cells/mm3 (1.0 x 109 /L), ii) PLT count ≥ 75,000 cells/mm3 (75 x 109 /L) iii) Hb ≥ 7.5 g/dL

• estimated glomerular filtration rate (eGFR) ≥ 30 ml/min/1.73m².
• Serum aspartate transaminase (AST/SGOT) or alanine transaminase (ALT/SGPT) ≤ 2.5 x upper limit of normal (ULN). In case of documented liver involvement by lymphoma, ALT/SGPT and AST/SGOT must be ≤ 5.0× ULN.
• Serum total bilirubin ≤ 1.5 × 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 ≤ 3.0 × ULN (corresponding to moderate dysfunction as per NCI ODWG criteria). For cases of Gilberts syndrome, serum total bilirubin≤ 5.0 × ULN.
• Adequate cardiac function for participants receiving anthracycline-based chemotherapy, defined as left ventricular ejection fraction (LVEF) ≥ 45% as assessed by echocardiogram (ECHO) as standard of care or multi-gated acquisition scan (MUGA).

Критерии исключения

• Evidence or history of composite Diffuse large B-cell lymphoma (DLBCL) and FL or of transformed Non-Hodgkin Lymphoma (NHL), including history of prior large B-cell lymphomas (LBCL), 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/Pulmonary embolism within 1 month prior to enrollment.
• Participants with a history of progressive multifocal leukoencephalopathy.
• Participant has any other subtype of lymphoma.
• Participant has persistent diarrhea or malabsorption ≥ Grade 2 (NCI CTCAE v5.0), despite medical management.
• History of another primary malignancy that has not been in remission for ≥ 3 years except for non-invasive malignancies.
• Other protocol-defined Inclusion/Exclusion criteria apply.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 31 центр

• Local Institution - 0225 — Birmingham
• Infirmary Cancer Care — Mobile
• Alaska Oncology and Hematology — Anchorage
• Local Institution - 0215 — Little Rock
• City of Hope Comprehensive Cancer Center — Duarte
• UCSF Helen Diller Medical Center at Parnassus Heights — San Francisco
• Local Institution - 0008 — Jacksonville
• Local Institution - 0214 — Tampa
• … и ещё 23 центра

Китай · 23 центра

• Local Institution - 0246 — Пекин
• Beijing Cancer hospital — Пекин
• Local Institution - 0172 — Fuzhou Fujian
• Sun Yat-sen University Cancer Center — Гуанчжоу
• Local Institution - 0241 — Харбин
• Union Hospital Tongji Medical College Huazhong University of Science and Technology — Ухань
• Local Institution - 0175 — Чанша
• Inner Mongolia Cancer Hospital — Hohhot
• … и ещё 15 центров

Германия · 14 центров

Список центров уточняется — проверьте первичный протокол.

Япония · 10 центров

Список центров уточняется — проверьте первичный протокол.

Франция · 8 центров

• CHU Bordeaux Haut-Leveque — Pessac
• … и ещё 7 центров

Австралия · 7 центров

• Westmead Hospital — Westmead
• Local Institution - 0132 — Adelaide
• Local Institution - 0131 — Hobart
• Local Institution - 0128 — Heidelberg
• Cabrini Hospital - Malvern — Malvern
• Local Institution - 0127 — Perth
• Local Institution - 0224 — Perth

Бразилия · 7 центров

• Local Institution - 0159 — Vitória
• Local Institution - 0088 — Niterói
• Local Institution - 0087 — Porto Alegre
• Local Institution - 0079 — São Paulo
• Local Institution - 0089 — Rio de Janeiro
• Local Institution - 0066 — São Paulo
• Local Institution - 0092 — São Paulo

Италия · 7 центров

Список центров уточняется — проверьте первичный протокол.

Греция · 6 центров

Список центров уточняется — проверьте первичный протокол.

Испания · 6 центров

Список центров уточняется — проверьте первичный протокол.

Канада · 5 центров

• Local Institution - 0200 — Victoria
• Princess Margaret Cancer Centre — Toronto
• Local Institution - 0250 — Québec
• Local Institution - 0192 — Sherbrooke
• Local Institution - 0226 — Sherbrooke

Индия · 5 центров

Список центров уточняется — проверьте первичный протокол.

Польша · 5 центров

Список центров уточняется — проверьте первичный протокол.

South Korea · 4 центра

Список центров уточняется — проверьте первичный протокол.

Turkey (Türkiye) · 4 центра

Список центров уточняется — проверьте первичный протокол.

Великобритания · 4 центра

Список центров уточняется — проверьте первичный протокол.

Чили · 3 центра

• Local Institution - 0154 — Santiago
• Local Institution - 0155 — Santiago
• Local Institution - 0153 — Santiago

Финляндия · 3 центра

• Local Institution - 0151 — Oulu
• Local Institution - 0152 — Turku
• Local Institution - 0150 — Helsinki

Нидерланды · 3 центра

Список центров уточняется — проверьте первичный протокол.

Саудовская Аравия · 3 центра

Список центров уточняется — проверьте первичный протокол.

ОАЭ · 2 центра

Список центров уточняется — проверьте первичный протокол.

Идентификаторы

NCT: NCT06911502 · CA073-1003 · 2024-519152-82 · U1111-1314-3909

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗