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 (GOLSEEK-4)

Celgene

Status and phase: Begins enrollment in 2 months; Phase 3

Conditions: Follicular Lymphoma

Treatments: Drug: Golcadomide; Drug: Rituximab; Drug: Prednisone/Prednisolone; Drug: Cyclophosphamide; Drug: Bendamustine; Drug: Doxorubicin; Drug: Vincristine; Drug: Lenalidomide

Study type: Interventional

Funder types: Industry

Identifiers

NCT06911502

CA073-1003

U1111-1314-3909 (Other Identifier)

2024-519152-82 (Other Identifier)

Details and patient eligibility

About

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.

Enrollment: 400 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Participant has histologically confirmed FL (Grade 1, 2, or 3a) 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:

  1. Relapsed FL is defined as relapse after an initial response of CR or PR to the most recent prior therapy.
  2. Refractory FL is defined as best response of SD or PD 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:

  1. Absolute neutrophil count (ANC) ≥ 1,000 cells/mm3 (1.0 x 109 /L),
  2. PLT count ≥ 75,000 cells/mm3 (75 x 109 /L)
  3. 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) ≥ 40% as assessed by echocardiogram (ECHO) as standard of care or multi-gated acquisition scan (MUGA)

Exclusion criteria

• Evidence or history of composite Diffuse large B-cell lymphoma (DLBCL) and FL or of transformed Non-Hodgkin Lymphoma (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/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.

• Participants who are refractory to both chemotherapies as well as lenalidomide, defined as:

  1. SD/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
  2. SD/progressive disease as best response to lenalidomide based regimen or a response to lenalidomide based regimen that lasted less than 6 months.

• Other protocol-defined Inclusion/Exclusion criteria apply.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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400 participants in 2 patient groups

Golcadomide + Rituximab

Experimental group

Treatment:

Drug: Rituximab

Drug: Golcadomide

Rituximab + Lenalidomide/Chemotherapy

Active Comparator group

Description:

Rituximab + Lenalidomide or R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone/prednisolone) or Rituximab + Bendamustine

Treatment:

Drug: Lenalidomide

Drug: Vincristine

Drug: Doxorubicin

Drug: Bendamustine

Drug: Cyclophosphamide

Drug: Prednisone/Prednisolone

Drug: Rituximab