Phase II Trials of Letermovir Prophylaxis in Patients With RRMM Undergoing Elranatamab Therapy

NCT06920251 | Recruiting Phase 2 DMC

• 1 other identifier: H-2503-044-1261
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

This is an open-label, single arm, multicenter study to evaluate the efficacy of letermovir in the prevention of clinically significant CMV infection in adult, CMV-seropositive relapsed/refractory MM patients undergoing BsAbs therapy.

Conditions

Relapsed Refractory Multiple Myeloma (RRMM)

Outcome Measures

Primary Outcomes (1)

• Proportion of subjects with clinically significant CMV infection during 6 cycles of elranatamab treatment

  Clinically significant CMV infection is defined as the occurrence of either one of the following outcomes: 1. onset of CMV end-organ disease or 2. initiation of anti-CMV pre-emptive therapy based on documented CMV viremia\* and the clinical condition of the subject. Initiation of pre-emptive therapy refers to the practice of initiating therapy with the following approved anti-CMV agents when active CMV viral replication is documented: ganciclovir, valganciclovir, foscarnet, and/or cidofovir. * Viral load threshold for initiating pre-emptive therapy is viral DNA ≥ 500 IU/mL in 2 consecutive assessments separated by at least 1 day, or, single viral DNA ≥ 1,000 IU/mL

  From Cycle 1 Day 1 to completion of Cycle 6 (Week 24; each cycle is 28 days)

Secondary Outcomes (5)

• Proportion of subjects with clinically significant CMV infection during 12 cycles of elranatamab treatment

  From Cycle 1 Day 1 to completion of Cycle 12 (each cycle is 28 days)

• Incidence of CMV disease during the first 6 and 12 cycles of elranatamab

  From Cycle 1 Day 1 to completion of Cycle 6 and Cycle 12, respectively (each cycle is 28 days)..

• Incidence of CMV viremia during the first 6 and 12 cycles of elranatamab

  From Cycle 1 Day 1 to completion of Cycle 6 and Cycle 12, respectively (each cycle is 28 days).

• Toxicity

  From Cycle 1 Day 1 to study completion, an average of 1 year.

• Tolerability

  From Cycle 1 Day 1 to study completion, an average of 1 year.

Study Arms (1)

Treatment arm

EXPERIMENTAL

This is an experimental cohort designed to evaluate the effectiveness of letermovir in reducing CMV infection in patients with relapsed or refractory multiple myeloma (RRMM) undergoing Elranatamab treatment. Letermovir is administered from Cycle 1 Day 15 (Week 3) to Cycle 4 (Week 16), for a total duration of 98 days.

Drug: Letermovir

Interventions

Letermovir DRUG

Elranatamab: Participants will receive SC administration of elranatamab QW, Q2W or Q4W. The initial doses of elranatamab will be 12 mg (C1D1) and 32 mg (C1D4) and will serve as the 2 step-up priming regimen. Dexamethasone: Dexamethasone is administered at the dose of 20 mg/day on C1D1, C1D4 and C1D8 as a premedication for elranatamab Letermovir: Letermovir is administered at the dose of 480mg/day PO from C1D15 (W3) to C4 (W16) (total of 98 days).

Also known as: Elranatamab

Treatment arm

Eligibility Criteria

• Age: 19 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects must satisfy the following criteria to be enrolled in the study:
• Subject is ≥ 19 years of age at the time of signing the informed consent form (ICF).
• Subject must understand and voluntarily sign an ICF prior to any study-related assessments/procedures being conducted.
• Subject is willing and able to adhere to the study visit schedule and other protocol requirements.
• ④ Subjects have documented seropositivity for CMV (CMV IgG seropositvity) at any point. CMV IgG status will be re-checked during screening.
• ⑤ Subject has documented diagnosis of MM and measurable disease, defined as any of the following: A. M-protein ≥ 0.5 g/dL by serum protein electrophoresis (sPEP) or B. M-protein ≥ 200 mg/24-hour urine collection by urine protein electrophoresis (uPEP) or C. For subjects without measurable disease in sPEP or uPEP: serum free light chain (sFLC) levels \> 100 mg/L (10 mg/dL) involved light chain and an abnormal kappa/lambda FLC ratio.
• \*Patients with extramedullary disease (EMD) only will be allowed to participate if there is a measurable extramedullary lesion. These patients require PET-CT follow-up for response evaluation.
• ⑥ Subject has received 3 or more prior lines of antimyeloma therapy. (Note: One line can contain several phases \[e.g., induction, (with or without) hematopoietic stem cell transplant, (with or without) consolidation, and/or (with or without) maintenance therapy).
• ⑦ Subject must have received at least one proteasome inhibitor, one immunomodulatory drug, and one anti-CD38 antibody.
• Subject must have documented disease progression during or after their last antimyeloma regimen.
• Subject has an Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1 or 2.
• Individual of childbearing potential (IOCBP) must:
• A. Have two negative pregnancy tests as verified by the investigator prior to starting study treatment. She must 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.
• B. 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, 2 forms of contraception: one highly effective, and one additional effective (barrier) measure of contraception without interruption 28 days prior to starting study treatment, during the study treatment (including dose interruptions), and for at least 90 days after the last dose of letermovir or 4 months after the last dose of elranatamab, whichever is longer.
• ⑪ Male subjects must: A. Practice true abstinence\* (which must be reviewed on a monthly basis) or agree to use a condom during sexual contact with a pregnant individual or an individual of childbearing potential while participating in the study, during dose interruptions and for at least 90 days after the last dose of letermovir, even if he has undergone a successful vasectomy.

You may not qualify if:

• The presence of any of the following will exclude a subject from enrollment:
• Subject who has a history of CMV end-oragn disease within 6 months prior to enrollment.
• Subject who has evidence of CMV viremia at screening (D-7 CMV DNA results required - for specifics refer to section 5.3 and schedule of activities; SoA).
• Subject who has received within 7 days prior to screening or plans to receive during the study ant of the following:
• A. Ganciclovir B. Valganciclovir C. Foscarnet D. Acyclovir, at doses \> 3200mg PO per day or \> 25mg/kg IV per day E. Valacyclovir, at doses \> 3000mg PO per day F. Famciclovir, at doses \> 1500mg PO per day
• Subject who has suspected or known hypersensitivity to active or inactive ingredients of letermovir formulations.
• Subject has received any of the following. A. Plasmapheresis within the last 28 days of initiating study treatment B. Major surgery (as defined by the investigator) within 28 days of initiating study treatment.
• Subject has previously received allogeneic stem cell transplantation within a year during prior therapy or received autologous stem cell transplantation within 12 weeks of initiating study treatment. Patients who received allogeneic stem cell transplantation should not have evidence of active graft-versus-host disease (GVHD) and off any immunosuppressants.
• Subject has plasma cell leukemia defined by IMWG definition for primary plasma cell leukemia, Waldenstrom's macroglobulinemia, POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes) or clinically significant light-chain amyloidosis.
• Subject with known central nervous system (CNS) involvement with myeloma.
• Subject has any significant medical condition, including active or uncontrolled infection, presence of laboratory abnormality, or psychiatric illness that places the subject at an unacceptable risk for treatment-related complications, if he/she were to participate in the study.
• Coronavirus disease 2019 (COVID-19) within 7 days for mild or asymptomatic infections or 14 days for moderate/severe infections prior to initiating study intervention. A longer duration may be needed based on the investigator's clinical judgment.
• A. Acute symptoms must have resolved and there are no sequelae that would place the participant at a higher risk of receiving study intervention, based on investigator assessment. No repeat/follow-up COVID-19 testing is required.
• Subject has any condition that confounds the ability to interpret data from the study.
• Subject has any of the following laboratory abnormalities:

Sponsors & Collaborators

• Seoul National University Hospital: lead

Study Sites (1)

Seoul National University Hospital

Seoul, South Korea

RECRUITING

MeSH Terms

Conditions

Multiple Myeloma

Interventions

letermovir

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Central Study Contacts

Ja Min Byun, MD, PhD

CONTACT

82-2-2072-7215; jaminbyun@snu.ac.kr

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor, MD, PhD

Study Record Dates

• First Submitted: March 26, 2025
• First Posted: April 9, 2025
• Study Start: September 11, 2025
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2028
• Last Updated: December 3, 2025

Record last verified: 2025-11

Locations

KR (1)