GOLCADOMIDE for Diffuse large B-cell lymphoma | High-risk large B-cell lymphoma

Inclusion criteria

• {"criterion_text":"-Signed Written Informed Consent"}
• {"criterion_text":"-Type of Participant and Target Disease Characteristics •\tHistologically confirmed (per local evaluation) diagnosis of de novo, previously untreated LBCL according to 2022 WHO classification including: i) DLBCL, NOS (including GCB and ABC types) ii) High-grade B-cell lymphoma, with MYC and BCL2 rearrangements (HGBL-MYC/BCL2 double hit lymphoma) iii) High-grade B-cell lymphoma, NOS iv) T-cell/histiocyte/rich large B-cell lymphoma v) Epstein-Barr virus + DLBCL •\tParticipant has: i) IPI score 1 or 2 with LDH > 1.3 x ULN and/or bulky disease defined as single lesion of ≥ 7 cm OR ii) IPI ≥ 3 •\tAt least one bi-dimensionally measurable lesion, defined as >1.5 cm in its longest dimension as measured by CT. •\tECOG PS of 0, 1, or 2. ECOG PS 3 is allowed if it is disease related and not due to comorbidities. •\tAnn Arbor Stage II-IV disease. •\tAbsolute neutrophil count (ANC) ≥ 1.0 × 109/L and Platelets (PLT) ≥ 75 × 109/L unless due to lymphoma. •\tHemoglobin ≥ 75 g/L. •\tAspartate aminotransferase (AST)/ serum glutamic oxaloacetic transaminase (SGOT) and alanine aminotransferase (ALT)/serum glutamate pyruvic transaminase (SGPT) ≤ 2.5 × ULN. In case of documented liver involvement by lymphoma, ALT/SGPT and AST/SGOT must be ≤ 5.0 × ULN. •\tSerum total bilirubin ≤ 1.5 × ULN. In case of documented liver involvement by lymphoma, serum total bilirubin must be ≤ 3.0 × ULN. For cases of Gilbert syndrome, then serum total bilirubin ≤ 5 × ULN. •\tEstimated serum creatinine clearance (CrCl) of ≥ 30 mL/min using the modification of diet in renal disease (MDRD) formula The same CrCl cutoff applies in case of documented renal involvement by lymphoma. •\tAgree to receive pregnancy counseling and adhere to all requirements defined in the Pregnancy Prevention Program •\tWilling and able to adhere to the study visit schedule and other protocol requirements."}
• {"criterion_text":"-Participant must be 18 to 80 years of age"}

Exclusion criteria

• {"criterion_text":"-Medical Conditions a) Participant has any significant medical condition, active infection, laboratory abnormality, or psychiatric illness that would prevent the participant from participating in the study. b) Participant has any other subtype of lymphoma. •\tCases of primary mediastinal (thymic) large B-cell lymphoma •\tPrimary cutaneous DLBCL-leg type, •\tGrade 3b follicular lymphoma (FL), •\tindolent lymphoma transformed to LBCL, •\tALK-positive large B cell lymphoma, •\tprimary effusion lymphoma, or •\tBurkitt lymphoma are excluded. c) CNS involvement at diagnosis. d) Participant has persistent diarrhea or malabsorption ≥ Grade 2 (despite medical management). e) Peripheral neuropathy ≥ Grade 2 f) Participant has impaired cardiac function or clinically significant cardiac disease. g) Any other prior malignancy unless being free of the disease for ≥ 3 years; other than Localized nonmelanoma skin cancer, Carcinoma in situ of the cervix, Carcinoma in situ of the breast, Incidental histologic finding of prostate cancer (T1a or T1b as per Tumor Node Metastasis staging system) or prostate cancer that has been treated with curative intent. v)History of other early-stage malignancy appropriately treated with curatively intent that does not confound study results. Such cases should be discussed with the Medical Monitor"}
• {"criterion_text":"-Individuals who are breastfeeding"}
• {"criterion_text":"-Prior/Concomitant Therapy a) Inability to comply with restrictions and prohibited treatments b) Participant is on chronic systemic immunosuppressive therapy or corticosteroids c) Current treatment with strong cytochrome P450 3A4/5 (CYP3A4/5) modulators. ) The washout period for strong CYP3A4/5 modulators is 7 days or 5 half-lives (whichever is longer) before initiation of golcadomide. d) Unwilling to take venous thromboembolism (VTE) prophylaxis. e) Received live attenuated vaccines or live coronavirus disease 2019 (COVID-19) vaccines within 30 days prior to initiation of study treatment."}
• {"criterion_text":"-Physical and Laboratory Test Findings a) Evidence of organ dysfunction or any clinically significant deviation from normal in physical examination, b) Seropositivity for or active viral infection with human immunodeficiency virus (HIV). c) Chronic active hepatitis B or C infection. d) Condition including the presence of laboratory test result abnormalities, which places the participant at unacceptable risk if he/she were to participate in the study. e) Participant had major surgery ≤ 2 weeks prior to starting golcadomide; f) Participant has any condition causing inability to swallow tablets."}
• {"criterion_text":"-Allergies and Adverse Drug Reactions a) Known allergy/hypersensitivity to any component (including excipients) of the study intervention or related compounds or significant drug allergy b) Known hypersensitivity to the active substance or to murine proteins, or to any of the other excipients of rituximab. c) Known hypersensitivity to any component of CHOP regimen. d) Known allergy to thalidomide, pomalidomide, or lenalidomide."}
• {"criterion_text":"-Other Exclusion Criteria Participation in another clinical trial concurrent with this study"}

Primary endpoints

• {"endpoint_text":"-To evaluate the PFS. This is the time from when a person starts the trial until their disease gets worse or they pass away, whichever happens first.","definition_or_measurement_approach":"Progression-Free Survival (PFS): time from randomisation / start of trial until objective disease progression or death from any cause, whichever occurs first (as described in main objective)."}

Secondary endpoints

• {"endpoint_text":"-To evaluate the OS. This is the time from when a person starts the trial until they pass away from any cause.","definition_or_measurement_approach":"Overall Survival (OS): time from randomisation / start of trial until death from any cause."}
• {"endpoint_text":"-To evaluate the EFS. This is the time from when a person starts the trial until one of the following happens: they pass away, their disease gets worse or comes back, they start a new treatment for their lymphoma, or they show signs of disease after finishing the treatment.","definition_or_measurement_approach":"Event-Free Survival (EFS): time from randomisation / start of trial to first of: death, disease progression/recurrence, initiation of new lymphoma therapy, or signs of disease after end of treatment."}
• {"endpoint_text":"-To evaluate the CMR. This means that at the end of the treatment, the person's disease has completely responded to the treatment.","definition_or_measurement_approach":"Complete Metabolic Response (CMR): absence of metabolic evidence of disease at end of treatment on appropriate imaging (as defined in protocol)."}
• {"endpoint_text":"-To evaluate the MRD negativity. This means that at the end of the treatment, we can't detect any cancer DNA in the person's body.","definition_or_measurement_approach":"Minimal Residual Disease (MRD) negativity: absence of detectable tumor-derived DNA in blood at end of treatment per the MRD assay specified in protocol."}

Primary sponsor

Full Name

Celgene Corp.

Organisation Type

Pharmaceutical company

Country Of Registered Address

United States

Contract research organisations

Name

IQVIA Laboratories Limited

Responsibilities

Sample management, kit building, storage and distribution of samples to vendors for analysis, immunophenotyping

Name

Medidata Solutions Inc.

Responsibilities

Data management / electronic data capture services

Name

Signant Health Global LLC

Responsibilities

IVRS – treatment randomisation, PRO/COA

Name

Omnitrace Corp.

Responsibilities

Lost / follow-up patient tracking

Name

Prometrika LLC

Responsibilities

Data Monitoring Committee (DMC) services

Name

QPS LLC

Responsibilities

PK analyses

Name

Cerba Research

Responsibilities

Routine clinical pathology testing, clinical chemistry, haematology, microbiology, histopathology

Third parties

• {"country":"Belgium","full_name":"Cerba Research","duties_or_roles":"Routine clinical pathology testing, Clinical chemistry, Clinical haematology, Clinical microbiology, Histopathology, Ailolos/Ikaros","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"Germany","full_name":"Azenta Germany GmbH","duties_or_roles":"Long term Sample storage for any samples throughout the study as well as any of the residual samples.","organisation_type":"Pharmaceutical company"}
• {"country":"India","full_name":"Accenture Solutions Private Limited","duties_or_roles":"Pharmacovigilance: Medical review & Cases Data Entry. / Embarc operations (multiple entries)","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"Iqvia Laboratories Limited","duties_or_roles":"Smpl mgmt, Kit building, Storage-distrib of samples to vendors for analysis, Immunophenotyping","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"Q2 Solutions","duties_or_roles":"Routine clin pathology testing, Clin chemistry, Clin haematology, Clin microbiology, Histopathology, Serology/endocrinology, Analytical chemistry, ECG analysis/review, Smpl mgmt, Kit building, Storage-distrib of smpls to vendors for analysis, Immunophenotyping","organisation_type":"SME"}
• {"country":"United States","full_name":"Signant Health Global LLC","duties_or_roles":"IVRS – treatment randomisation, PRO/COA","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Omnitrace Corp.","duties_or_roles":"Lost of F-Up patients tracking","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United States","full_name":"Medidata Solutions Inc.","duties_or_roles":"Data management (application lists code 6 in sponsor duties)","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United States","full_name":"Yprime LLC","duties_or_roles":"Core Technology Services and related duties","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United States","full_name":"QPS LLC","duties_or_roles":"PK analyses","organisation_type":"Pharmaceutical company"}
• {"country":"India","full_name":"Accenture Services Pvt. Ltd.","duties_or_roles":"Pharmacovigilance duties: Medical review and Cases Data Entry","organisation_type":"SME"}
• {"country":"United States","full_name":"Greenphire LLC","duties_or_roles":"Provides electronic payments, travel arrangements, electronic study-related communications to patients","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United States","full_name":"Clario","duties_or_roles":"Medical image analysis/review, IT Infrastructure and storage/Document Storage/Data Management/Archive/Translation Services, Cognitive Debriefing","organisation_type":"Industry"}
• {"country":"United States","full_name":"Prometrika LLC","duties_or_roles":"Data Monitoring Committee (DMC) services","organisation_type":"Pharmaceutical company"}