Ensayos clínicos

Inclusion Criteria:

• Participants must have signed and dated an Institutional Review Board (IRB)/Independent Ethics Committee (IEC)-approved written informed consent form (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
• Participant has histologically confirmed (per local evaluation) diagnosis of de novo, previously untreated LBCL according to 2022 WHO classification including:
  • DLBCL, NOS (including GCB and ABC types)
  • High-grade B-cell lymphoma, with MYC and BCL2 rearrangements
  • High-grade B-cell lymphoma, NOS
  • T-cell/histiocyte/rich large B-cell lymphoma
  • Epstein-Barr virus + DLBCL
• Participant has:
  • IPI score 1 or 2 with LDH ≥ 1.3 x ULN and/or bulky disease defined as single lesion of ≥ 7 cm OR
  •  IPI ≥ 3
  • NOTE: The number of patients with IPI 1 or 2 with LDH ≥ 1.3 x ULN and/or bulky disease ≥ 7 cm will be capped at 25% of the total enrolled population
• Participants must have measurable disease defined by at least one fluorodeoxyglucose (FDG)-avid lesion for FDG-avid subtype and one bi-dimensionally measurable (> 1.5 cm in longest diameter) disease by computed tomography (CT) or magnetic resonance imaging (MRI), as defined by the Lugano classification
• Participant has an ECOG PS of 0, 1, or 2. ECOG PS 3 is allowed if it is disease related and not due to comorbidities.
• Participants must have Ann Arbor Stage II-IV disease
• Participants must have the following laboratory values:
  • Absolute neutrophil count ≥ 1.0 × 109 /L or ≥ 0.5 × 109 /L in case of documented bone marrow involvement or DLBCL-related hypersplenism present.
  • Hemoglobin ≥ 75 g/L. 
  • Platelets (PLT) ≥ 75 × 109 /L or ≥ 50 × 109 /L in case of documented bone marrow involvement or DLBCL-related hypersplenism present.
  • Aspartate 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.
  • 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 Gilbert syndrome, then serum total bilirubin ≤ 5 × ULN.
  • Estimated serum creatinine clearance (CrCl) of ≥ 45 mL/min using the modification of diet in renal disease (MDRD) formula or ≥ 30 mL/min in case of documented renal involvement by lymphoma.
• All participants must:
  • Agree to receive pregnancy counseling and adhere to all requirements defined in the Pregnancy Prevention Program for golcadomide: Pregnancy Prevention Plan for Participants in Clinical Trials.
  • Agree to refrain from donating blood while on study treatment, during dose interruptions, and for at least 28 days following the last dose of study treatment.
  • Agree not to share study medication with another person.
• Participant is willing and able to adhere to the study visit schedule and other protocol requirements.
• Participant must be 18 to 80 years of age, inclusive, at the time of signing the ICF.
• The investigator or designee shall counsel individuals of childbearing potential (IOCBP) participants 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.
• The investigator or designee shall evaluate the effectiveness of the contraceptive method in relationship to the first dose of study intervention.
• Local laws and regulations may require the use of alternative and/or additional contraceptive methods.
  • Female (as assigned at birth) participants must adhere to Pregnancy Prevention Plan requirements including:
    • Female (as assigned at birth) participants who are not of childbearing potential must have documented proof. Note: Documentation can be obtained from the site personnel’s review of the participant’s medical records, medical examination, or medical history interview. Individuals who are not of childbearing potential are exempt from contraceptive requirements.
    • 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, at least 2 effective contraceptive methods (oral, injectable, or implantable hormonal contraceptive; tubal ligation; intrauterine device; barrier contraceptive with spermicide; or vasectomized partner), which must include one highly effective method and one additional (barrier) method, from signing the ICF, at least 28 days before starting golcadomide, throughout the study, for up to 28 days following the last dose of golcadomide, and for 12 months after the last dose of rituximab, whichever is longer.
    • Have 2 negative pregnancy tests as verified by the Investigator prior to starting golcadomide:
      • A negative serum pregnancy test (sensitivity of at least 25 mIU/mL) at screening (between 10 to 14 days prior to Cycle 1 Day 1).
      • A negative serum or urine pregnancy test (sensitivity of at least 25 mIU/mL) 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.
    • Avoid conceiving for up to 28 days after the last dose of golcadomide
    • Agree to ongoing pregnancy testing during the course of the study, and after the end of study treatment. This applies even if the subject practices true abstinence from heterosexual contact.
    • Agree to refrain from donating ova while on golcadomide for at least 28 days after its discontinuation.
    • Agree to abstain from breastfeeding or providing breast milk while on golcadomide and 28 days after discontinuation of golcadomide and according to the approved rituximab product/prescribing information.
  • Male (as assigned at birth) participants:
    • Males (as assigned at birth) must adhere to Pregnancy Prevention Plan requirements (Appendix 4) including the practice of true abstinence (which must be reviewed on a monthly basis) or agree to use a condom (a latex condom is recommended) during sexual contact with a pregnant female or an IOCBP and will avoid conceiving from the date of signing the ICF, while participating in the study, during dose interruptions, and for at least 28 days following golcadomide discontinuation or 90 days for rituximab, whichever is longer, even if he has undergone a successful vasectomy.
    • 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 study intervention or 90 days for rituximab, whichever is longer, for the male participant.
    • 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 study intervention or 90 days for rituximab, whichever is longer.
    • Male participants must refrain from donating sperm during the intervention period and for at least 28 days after the last dose of study intervention or 90 days for rituximab, whichever is longer.
    • 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.

Exclusion Criteria:

• Medical Conditions
  • Participant has any significant medical condition, active infection, laboratory abnormality, or psychiatric illness that would prevent the participant from participating in the study.
  • Participant has any other subtype of lymphoma. Cases of primary mediastinal (thymic) large B-cell lymphoma, primary cutaneous DLBCL-leg type, Grade 3b follicular lymphoma (FL), FL transformed to activated B-cell lymphoma, ALK-positive large Bcell lymphoma, primary effusion lymphoma, or Burkitt lymphoma are excluded.
  • Participant has documented or suspected central nervous system (CNS) involvement by lymphoma.
  • Participant has persistent diarrhea or malabsorption ≥ Grade 2 (National Cancer Institute Common Terminology Criteria for Adverse Events [NCI CTCAE] v5.0), despite medical management.
  • Participant has peripheral neuropathy ≥ Grade 2 (NCI CTCAE v5.0) 
  • Participant has impaired cardiac function or clinically significant cardiac disease, including any of the following:
    • Left ventricular ejection fraction < 45% as determined by multigated acquisition scan or echocardiogram (ECHO)
    • Heart failure (New York Heart Association Class III or IV)
    • Clinically significant abnormal electrocardiogram (ECG) finding at screening
    • Unstable angina or myocardial infarction ≤ 6 months prior to starting study treatment
    • Persistent or uncontrolled ventricular arrhythmias or atrial fibrillation or cardiac conduction abnormalities not mitigated by a pacemaker
  • Participant has history of other malignancy, unless being free of the disease for ≥ 3 years; exceptions to the ≥ 3-year time limit include history of the following:
    • 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
• Reproductive Status
  •  Individuals who are breastfeeding
• Prior/Concomitant Therapy
  • Inability to comply with restrictions and prohibited treatments
  • Participant is on chronic systemic immunosuppressive therapy or corticosteroids (prednisone or equivalent not to exceed 10 mg per day within the last 14 days is allowed); stable use of inhaled or topical corticosteroids is allowed. Corticosteroid treatment as a part of prephase is allowed.
  • Participant has current treatment with strong cytochrome P450 3A4/5 (CYP3A4/5) modulators.
  • Participants who are unwilling to take venous thromboembolism (VTE) prophylaxis.
  • Participant received live attenuated vaccines or live coronavirus disease 2019 (COVID19) vaccines within 30 days prior to initiation of study treatment.
• Physical and Laboratory Test Findings
  • 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.
  • 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 and/or hepatitis B core antibody [anti-HBc] positive with viral DNA positive) or C (positive serology requiring treatment and/or with evidence of liver damage) infection.
  • Participant has any 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.
  • Participant had major surgery ≤ 2 weeks prior to starting golcadomide; participant must have recovered from any clinically significant effects of recent surgery.
  • Participant has any condition causing inability to swallow tablets.
• Allergies and Adverse Drug Reactions
  • History of allergy/hypersensitivity to any component (including excipients) of the study intervention or related compounds.
  • History of any significant drug allergy (such as anaphylaxis or hepatotoxicity)
  • Participant has known hypersensitivity to the active substance or to murine proteins, or to any of the other excipients of rituximab.
  • Participant has known hypersensitivity to any component of CHOP regimen.
  • Participant has known allergy to thalidomide, pomalidomide, or lenalidomide.
• Other Exclusion Criteria
  • 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 may be included or permitted to continue as a participant. Strict conditions apply, and Sponsor approval is required.)
  • Participation in another clinical trial concurrent with this study

Note: Other protocol defined Inclusion/Exclusion Criteria may apply.

Eligibility last updated 3/15/2024. Questions regarding updates should be directed to the study team contact.