Letermovir for the Prevention of Cytomegalovirus Reactivation in Patients With Hematological Malignancies Treated With Alemtuzumab

NCT04312841 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: OSU-19289NCI-2020-00169
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

Brief Summary

This phase II trial studies how well letermovir works for the prevention of cytomegalovirus reactivation in patients with hematological malignancies treated with alemtuzumab. Patients receiving treatment with alemtuzumab may experience cytomegalovirus reactivation. Letermovir may block cytomegalovirus replication and prevent infection.

Conditions

B-Cell Prolymphocytic Leukemia; Chronic Lymphocytic Leukemia; Peripheral T-Cell Lymphoma; Primary Cutaneous T-Cell Non-Hodgkin Lymphoma; Sezary Syndrome; T-Cell Prolymphocytic Leukemia

Outcome Measures

Primary Outcomes (1)

• Cytomegalovirus (CMV) Reactivation

  Defined as the proportion of patients who experience CMV reactivation (CMV deoxyribonucleic acid \[DNA\] by real time polymerase chain reaction \> 500 IU/mL) during prophylaxis period among all patients who receive \>= 90% of planned letermovir doses. The rate will be provided with 95% binomial confidence interval.

  During prophylaxis treatment (3 months after last dose of alemtuzumab)

Secondary Outcomes (4)

• Number of Participants With Adverse Events Grade 3 or Above

  Up to 30 days post treatment, an average of 5 months

• Development of CMV Disease

  Up to 2 years

• Progression Free Survival (PFS)

  From trial enrollment to the occurrence of progression and death, assessed up to 2 years

• Overall Survival (OS)

  From trial enrollment to the occurrence of death due to any cause, assessed up to 2 years

Other Outcomes (1)

• Genotyping of Mutations in CMV Terminase Complex Genes

  Up to 2 years

Study Arms (1)

Treatment (letermovir)

EXPERIMENTAL

Beginning within 7 days of the first administration of standard alemtuzumab, patients receive letermovir PO (or IV over 1 hour if patient is unable to take PO for an extended period of time) daily on days 1-28. Cycles repeat every 28 days for up to 3 months after the last dose of alemtuzumab in the absence of unacceptable toxicity.

Drug: Letermovir

Interventions

Letermovir DRUG

Given PO

Also known as: 2-((4S)-8-Fluoro-2-(4-(3-methoxyphenyl)piperazin-1-yl)-3-(2-methoxy-5-(trifluoromethyl)phenyl)-4H-quinazolin-4-yl)acetic Acid, AIC246, MK-8228, Prevymis

Treatment (letermovir)

Eligibility Criteria

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

You may qualify if:

• Confirmed diagnosis of T-cell or B-cell prolymphocytic leukemia, chronic lymphocytic leukemia, peripheral T-cell lymphoma, cutaneous T-cell lymphoma, or Sezary syndrome
• Intent to treat with alemtuzumab. Monotherapy or combination with chemotherapy is allowed
• Confirmed seropositivity for CMV IgG (\>= 0.7 U/mL) within 1 year of first letermovir dose
• Confirmed lack of active CMV infection as evidenced by:
• Undetectable CMV deoxyribonucleic acid (DNA) by Abbott RealTime CMV in vitro polymerase chain reaction assay (\< 50 IU/mL) within 7 days of first letermovir dose AND
• Negative CMV IgM (\< 30 AU/mL) within 7 days of first letermovir dose
• Able to provide informed consent
• Life expectancy \> 4 months
• Eastern Cooperative Oncology Group (ECOG) performance status =\< 3
• Highly unlikely to become pregnant or impregnate a partner by meeting at least one of the following:
• A female subject who is not of reproductive potential is eligible without requiring the use of contraception. A female subject who is not of reproductive potential is defined as one who:
• Has reached natural menopause (defined as 6 months of spontaneous amenorrhea with serum follicle-stimulating hormone \[FSH\] levels in the postmenopausal range as determined by the local laboratory, or 12 months of spontaneous amenorrhea) OR
• Is 6 weeks post-surgical bilateral oophorectomy with or without hysterectomy OR
• Has undergone bilateral tubal ligation. Spontaneous amenorrhea does not include cases for which there is an underlying disease that causes amenorrhea (e.g., anorexia nervosa)
• A male subject who is not of reproductive potential is eligible without requiring the use of contraception. A male subject who is not of reproductive potential is defined as one whom has undergone a successful defined as:

You may not qualify if:

• History of confirmed CMV disease within 1 year of study entry
• History of prior allogeneic hematopoietic stem cell transplant
• End stage renal disease with creatinine clearance \< 10 mL/min as defined by Cockcroft-Gault equation using serum creatinine within 7 days of enrollment
• Child-Pugh class C within 7 days of enrollment
• Serum aspartate aminotransferase (AST) or alanine aminotransferase (ALT) \> 5 times the upper limit of normal (ULN) or serum total bilirubin \> 2.5 x ULN
• Both moderate hepatic insufficiency AND moderate renal insufficiency:
• Moderate hepatic insufficiency is defined as Child Pugh Class B
• Moderate renal insufficiency is defined as a creatinine clearance less than 50 mL/min, as calculated by the Cockcroft-Gault equation
• Received any of the following drugs within 7 days of enrollment or plans to receive any of the following during the study:
• Ganciclovir
• Valganciclovir
• Foscarnet
• Acyclovir (at doses \> 3200 mg PO per day or \> 25 mg/kg IV per day)
• Valacyclovir (at doses \> 3000 mg PO per day)
• Famciclovir (at doses \> 1500 mg PO per day)

Sponsors & Collaborators

• Ohio State University Comprehensive Cancer Center: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (1)

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210, United States

Location

Related Links

• The Jamesline

MeSH Terms

Conditions

Leukemia, Prolymphocytic, B-Cell; Leukemia, Lymphocytic, Chronic, B-Cell; Lymphoma, T-Cell, Peripheral; Lymphoma, T-Cell, Cutaneous; Sezary Syndrome; Leukemia, Prolymphocytic, T-Cell

Interventions

letermovir

Condition Hierarchy (Ancestors)

Leukemia, B-Cell; Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Leukemia, Prolymphocytic; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Lymphoma, T-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Leukemia, T-Cell

Results Point of Contact

• Title: Dr. John Reneau
• Organization: The Ohio State University Comprehensive Cancer Center

John.Reneau@osumc.edu

614-293-3196

Study Officials

• John C Reneau, MD

  Ohio State University Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: March 16, 2020
• First Posted: March 18, 2020
• Study Start: September 15, 2020
• Primary Completion: November 24, 2023
• Study Completion: April 9, 2024
• Last Updated: February 28, 2025
• Results First Posted: July 18, 2024

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)