C833 Diffuse large B-cell lymphoma Diffuse large B-cell lymphoma
Conditions
Interventions
Zilovertamab vedotin (MK 2140): Powder, dose strength 60 mg/vial. Dose level 1.75 mg/kg by intravenous infusion every 3 weeks for 6 cycles. Additionally, Rituximab, Cyclophosphamide, Doxorubicin and P
Sponsors
Merck Sharp & Dohme LLC., (una subsidiaria de Merck & Co. Inc.)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Has an IPI score of 2 to 5 assessed within 7 days before randomization. Note: enrollment of participants with an IPI score of 2 will be capped at 30% per arm. Has an ejection fraction =45% as determined by either ECHO or MUGA. Type of Participant and Disease Characteristics: Histologically-confirmed diagnosis of DLBCL, by prior biopsy, according to the WHO classification of neoplasms of the hematopoietic and lymphoid tissues [Swerdlow, S. H., et al 2016], which includes but is not limited to: DLBCL, NOS germinal center B-cell type, or activated B cell type; DLBCL leg-type; EBV+ DLBCL, NOS; and T-cell histiocytic-rich DLBCL. NOTE: HGBL participants will be excluded from this study. Has PET-positive disease at screening, defined as 4 to 5 on the Lugano 5 point scale. Has received no prior treatment for their DLBCL. Demographics: Is an individual of any sex/gender, =18 years of age at the time of providing documented informed consent. Assigned Male Sex at Birth: If capable of producing sperm, the participant agrees to the following during the intervention period and for at least the time needed to eliminate each study intervention after the last dose of study intervention. The length of time required to continue contraception for each study intervention is: - Zilovertamab vedotin: 110 days - Cyclophosphamide: 90 days - Doxorubicin: 90 days - Rituximab (or biosimilar): no contraception needed - Vincristine: 110 days • Refrains from donating sperm PLUS either: • Abstains from penile-vaginal intercourse as their preferred and usual lifestyle (abstinent on a long-term and persistent basis) and agrees to remain abstinent. OR • Uses a penile/external condom when having penile-vaginal intercourse with a nonparticipant of childbearing potential who is not currently pregnant PLUS partner use of an additional contraceptive method (refer to Section 10.5.3), as a condom may break or leak. Contraceptive use should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. If the contraception requirements in the local label for any of the study interventions are more stringent than the requirements above, the local label requirements are to be followed. Note: If the participant is azoospermic (vasectomized or secondary to medical cause, documented from the site personnel’s review of the participant’s medical records, medical examination, or medical history interview), no contraception is required. Assigned Female Sex at Birth: A POCBP is eligible to participate if not pregnant and a negative highly sensitive pregnancy test (urine or serum), as required by local regulations, within 24 hours (for a urine test) or 72 hours (for a serum test) before the first dose of study intervention has been obtained. If a urine test cannot be confirmed as negative (eg, an ambiguous result), a serum pregnancy test is required. Additional requirements for pregnancy testing during and after study intervention are in Section 8.3.5. A POCBP is eligible to participate if not breastfeeding during the study intervention period and for at least 180 days or 210 days after study intervention in Arm 1 and Arm 2, respectively. A POCBP is eligible to participate if a contraceptive method that is highly effective (with a failure rate of <1% per year), with low user dependency is used, or penile-vaginal intercourse abstinence, as their preferred and usual lifestyle (abstinent on a long-term and persistent basis), is adhered
Exclusion criteria
Exclusion criteria: Medical Conditions: Has a history of transformation of indolent disease to DLBCL. Has received a diagnosis of PMBCL or Grey zone lymphoma. Has Ann Arbor Stage I DLBCL. Has clinically significant (ie, active) cardiovascular disease: cerebral vascular accident/stroke (480 msec. Has clinically significant pericardial or pleural effusion. Has ongoing Grade >1 peripheral neuropathy. Has a demyelinating form of Charcot-Marie-Tooth disease. HIV-infected participants with a history of Kaposi’s sarcoma and/or Multicentric Castleman’s Disease. Prior/Concomitant Therapy: Has ongoing corticosteroid therapy (exceeding 30 mg daily of prednisone equivalent). Prednisone equivalent dosing must have been stable for at least 28 days prior to randomization. Note: If corticosteroid treatment is required for lymphoma symptom control prior to C1D1, up to 100 mg per day of prednisone equivalent can be given for up to 5 days. All tumor assessments must have been completed prior to the start of corticosteroid treatment. Received a live or live-attenuated vaccine within 30 days before the first dose of study intervention. Administration of killed vaccines is allowed. Refer to Section 6.5 for information on COVID-19 vaccines. Known intolerance to any of the study interventions and/or their excipients. Received a strong inhibitor or inducer of CYP3A4 within 14 days prior to randomization or is expected to require chronic use of a strong CYP3A4 inhibitor during treatment study intervention until 30 days after the last dose (see Section 6.5.2). Note: For participants requiring antifungal prophylaxis/therapy, oral fluconazole or isavuconazonium can be considered. Echinocandins (eg, caspofungin, anidulafungin, or micafungin) are also acceptable, realizing the disadvantage of the requirement for IV administration. Note: For examples of CYP3A4 induces and inhibitors, refer to https://www.fda.gov/drugs/drug-interactions-labeling/drug-development-and-drug-interactions-table-substrates-inhibitors-and-inducers Received a strong modulator of CYP2D6 or P-gp within 14 days prior to randomization or is expected to require chronic use of a modulator of CYP2D6 or P-gp during treatment study intervention until 30 days after the last dose (see Section 6.5.2). Note: For examples of modulators of CYP2D6 and P-gp, refer to https://www.fda.gov/drugs/drug-interactions-labeling/drug-development-and-drug-interactions-table-substrates-inhibitors-and-inducers Prior/Concurrent Clinical Study Experience: Has received an investigational agent or has used an investigational device within 4 weeks prior to study intervention administration. Diagnostic Assessments: Known additional malignancy that is progressing or has required active treatment within the past 2 years. Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ, excluding carcinoma in situ of the bladder, that have undergone potentially curative therapy are not excluded. Known active CNS lymphoma. Active autoimmune disease that has required systemic treatment in the past 2 years. Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid) is allowed. Active infection requiring systemic therapy. Concurrent
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Stratified log-rank test Estimation: Stratified Cox model with Efron’s tie handling method NAME OF THE RESULT: Progression-free survival (PFS) PERIOD OF TIME WHERE TE MEASUREMENT WILL BE CONDUCTED AND WHICH WILL ALLOW OBTAINING THE PRIMARY RESULT: Periodically from randomization until first documented disease progression according to RECIST 1.1 by central review blind independent (BICR) or death from any cause, whichever comes first. | — |
Secondary
| Measure | Time frame |
|---|---|
| Stratified log-rank test Estimation: Stratified Cox model with Efron’s tie handling method NAME OF THE RESULT: Progression-free survival (PFS) PERIOD OF TIME WHERE TE MEASUREMENT WILL BE CONDUCTED AND WHICH WILL ALLOW OBTAINING THE PRIMARY RESULT: Periodically from randomization until first documented disease progression according to RECIST 1.1 by central review blind independent (BICR) or death from any cause, whichever comes first.;Testing and estimation: stratified Miettinen and Nurminen method NAME OF THE RESULT: Complete Response at End of Treatment (CR at EOT) PERIOD OF TIME WHERE TE MEASUREMENT WILL BE CONDUCTED AND WHICH WILL ALLOW OBTAINING THE PRIMARY RESULT: At the end of treatment;Stratified log-rank test Estimation: Stratified Cox model with Efron’s tie handling method NAME OF THE RESULT: Overall Survival (OS) PERIOD OF TIME WHERE TE MEASUREMENT WILL BE CONDUCTED AND WHICH WILL ALLOW OBTAINING THE PRIMARY RESULT: From randomization to death due to any cause.;Stratified log-rank test Estimation: Stratified Cox model with Efron’s tie handling method NAME OF THE RESULT: Event-free survival (EFS) PERIOD OF TIME WHERE TE MEASUREMENT WILL BE CONDUCTED AND WHICH WILL ALLOW OBTAINING THE PRIMARY RESULT: From randomization to the first documented disease progression per Lugano response criteria by BICR, death due to any cause, initiation of a new anticancer therapy or a positive biopsy for residual disease, whichever occurs first;Kaplan-Meier medians and quartiles NAME OF THE RESULT: Duration of Complete Response (DurCR) PERIOD OF TIME WHERE TE MEASUREMENT WILL BE CONDUCTED AND WHICH WILL ALLOW OBTAINING THE PRIMARY RESULT: From the first documented evidence of CR at or before EOT until disease progression or death due to any cause, whichever occurs first. | — |
Countries
Argentina, Australia, Belgium, Brazil, Canada, Chile, China, Colombia, Denmark, France, Greece, Guatemala, Hong Kong, Hungary, Israel, Italy, Japan, Korea South, Malasya, Mexico, Nederland, Peru, Philippines, Poland, Puerto Rico, Romania, Singapore, South Africa, Spain, Switzerland, Taiwan, Thailand, Turkey, Ukraine, United States
Contacts
Public ContactNELVA GARCIA
MERCK SHARP & DOHME PERU S.R.L.
Outcome results
None listed