B-Cell Prolymphocytic LeukemiaPhase 2NCT04312841
Letermovir for the Prevention of Cytomegalovirus Reactivation in Patients With Hematological Malignancies Treated With Alemtuzumab
A Phase 2 study testing Letermovir in people with B-Cell Prolymphocytic Leukemia and Chronic Lymphocytic Leukemia, run by Ohio State University Comprehensive Cancer Center at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- B-Cell Prolymphocytic Leukemia, Chronic Lymphocytic Leukemia, Peripheral T-Cell Lymphoma
- What is being tested?
- Letermovir
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 6 participants
- Where
- 1 siteUnited States
- Study dates
- 15 Sep 2020to 9 Apr 2024
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Show all 19Show fewer
- 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:
- Microscopic documentation of azoospermia OR
- A vasectomy more than 2 years ago with no resultant pregnancy despite sexual activity post-vasectomy
- A male or female subject who is of reproductive potential agrees to true abstinence or to use (or have their partner use) an acceptable method of birth control starting from the time of consent through 90 days after the last dose of study therapy. True abstinence is defined as abstinence in line with the preferred and usual lifestyle of the subject. Periodic abstinence (e.g., abstinence only on certain calendar days, abstinence only during ovulation period, use of symptothermal method, use of post-ovulation methods) and withdrawal are not acceptable methods of contraception. Acceptable methods of birth control are:
- Intrauterine device (IUD), diaphragm with spermicide, contraceptive sponge, condom, and vasectomy OR use of appropriate double barrier contraception. Hormonal contraceptives (e.g., birth control pills, transdermal patch, or injectables) are also acceptable
Who cannot join
- 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
- Note: Subjects who meet this exclusion criterion may, at the discretion of the investigator, have one repeat testing done. If the repeat value does not meet this criterion, they may continue in the screening process. Only the specific out of range value should be repeated (not the entire panel)
Show all 36Show fewer
- 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
- Cytopenias are NOT an exclusion criteria in this trial as cytopenias are common in this patient population and letermovir has no known adverse effects on blood counts. Patients will be treated per institutional standard of care with as needed transfusions and growth factor support
- 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)
- Cyclosporine A
- Pimozide
- Ergot alkaloids (ergotamine and dihydroergotamine)
- Atorvastatin at doses greater than 20 mg daily
- Received any of the following within 30 days prior to enrollment
- Cidofovir
- CMV hyper-immune globulin
- Any investigational CMV antiviral agent/biologic therapy
- Infection or underlying disease necessitating ongoing use of prohibited medications
- Suspected or known hypersensitivity to active or inactive ingredients of letermovir formulations
- Positive at the time of screening for:
- Human immunodeficiency virus (HIV) with CD4 count < 350. If HIV positive, must remain on antiretroviral therapy that is not anticipated to interact with letermovir throughout study
- Hepatitis B surface antigen or core antibody positivity associated with detectable viral load. For any patient with serologic evidence of prior infection but undetectable viral load, viral load and surface antigen will be monitored every 2 weeks. Those with evidence of reactivation (detectable viral load) will be treated with entecavir or lamivudine. Upon resolution of detectable viral load, the patient will be allowed to continue on trial assuming adequate liver function as defined above. Alternatively, patients may be put on prophylactic entecavir or lamivudine to prevent hepatitis B reactivation at the investigator's discretion
- Hepatitis C if no prior or current curative antiviral therapy. For those currently on curative antiviral therapy, they will be allowed on trial if hepatitis C virus (HCV) quantitation is below the limit of detection and adequate liver function as above
- Pregnant or expecting to conceive, is breastfeeding, or plans to breastfeed from the time of consent through 90 days after the last dose of study therapy
- Expecting to donate eggs or sperm starting from the time of consent through 90 days after the last dose of study therapy
- Currently participating or has participated in a study with an unapproved investigational compound or device within 28 days, or 5X half-life of the investigational compound (excluding monoclonal antibodies), whichever is longer, of initial dosing on this study. Subjects previously treated with a monoclonal antibody will be eligible to participate after a 28-day washout period
- Previous participation in a study using letermovir
- Has a history or current evidence of any condition, therapy, lab abnormality, or other circumstance that might confound the results of the study, interfere with the subject's participation for the full duration of the study, or would be put at undue risk as judged by the investigator, such that it is not in the best interest of the subject to participate in this study
Trial locations and contacts
1 site in 1 country.
United States1 site
Ohio State University Comprehensive Cancer Center
Columbus, Ohio, 43210
About this study
Official title: Letermovir for Cytomegalovirus Prophylaxis in Patients With Hematological Malignancies Treated With Alemtuzumab
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.
Read the detailed description
PRIMARY OBJECTIVE:
- To estimate the rate of cytomegalovirus (CMV) reactivation in patients treated with letermovir at 3 months after completion of alemtuzumab therapy.
SECONDARY OBJECTIVES:
- To evaluate the tolerability of letermovir in combination with alemtuzumab.
II. To evaluate the efficacy of letermovir for the prevention of clinically significant CMV disease.
III. To estimate the progression free survival of patients in the study population.
IV. To estimate the overall survival of patients in the study population.
EXPLORATORY OBJECTIVE:
- To evaluate mechanisms of antiviral resistance in letermovir prophylaxis failures.
OUTLINE:
Beginning within 7 days of the first administration of standard alemtuzumab, patients receive letermovir orally (PO) (or intravenously [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.
After completion of study treatment, patients are followed up at 30 days.
- 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
- Being tested
- Letermovir
- Medical subject headings
- Leukemia, Prolymphocytic, B-Cell, Leukemia, Lymphocytic, Chronic, B-Cell, Lymphoma, T-Cell, Peripheral, Lymphoma, T-Cell, Cutaneous, Sezary Syndrome, Leukemia, Prolymphocytic, T-Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LetermovirDrug
Also called 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
Given PO
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Letermovir |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: During prophylaxis treatment (3 months after last dose of alemtuzumab)
Secondary outcomes (4)
Number of Participants With Adverse Events Grade 3 or Above
Adverse event data will be described and graded per the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0 guidelines. The maximum grade for each type of toxicity will be recorded for each patient, and frequency tables will be reviewed to determine toxicity patterns, especially for grade 3 or above adverse events. To assess tolerability, will also capture the proportion of patients who go off treatment due to adverse events.
Measured: Up to 30 days post treatment, an average of 5 months
Development of CMV Disease
Clinically significant CMV reactivation be determined per the Disease Definitions Working Group of the Cytomegalovirus Drug Development Forum.
Measured: Up to 2 years
Progression Free Survival (PFS)
PFS will be estimated with the method of Kaplan-Meier (KM), where KM curves will be drawn to aid with visualization and estimates provided with 95% confidence intervals.
Measured: From trial enrollment to the occurrence of progression and death, assessed up to 2 years
Overall Survival (OS)
OS will be estimated with the method of KM, where KM curves will be drawn to aid with visualization and estimates provided with 95% confidence intervals.
Measured: From trial enrollment to the occurrence of death due to any cause, assessed up to 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Mar 2020
- Study start15 Sep 2020
- Primary completion24 Nov 2023
- Study completion9 Apr 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for B-Cell Prolymphocytic LeukemiaStudies of the same condition, open and under way.
- More trials run by Ohio State University Comprehensive Cancer CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 6 participants (actual)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC
- Responsible party
- Principal investigator, John Reneau, Ohio State University Comprehensive Cancer Center
- Investigators
- John C Reneau, MD, Principal investigator, Ohio State University Comprehensive Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04312841
- Sponsor's protocol ID
- OSU-19289
- Other IDs
- NCI-2020-00169
- Status last verified
- Feb 2025
- First submitted
- 16 Mar 2020
- Last updated
- 28 Feb 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 28 Feb 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Letermovir for Cytomegalovirus Prophylaxis in Patients With Hematological Malignancies Treated With Alemtuzumab
- ClinicalTrials.gov ID
- NCT04312841
- Acronym / sponsor ID
- OSU-19289
- 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
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 6 participants (actual)
- Lead sponsor
- Ohio State University Comprehensive Cancer CenterUniversity, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC
- Study start
- 15 Sep 2020 (actual)
- Primary completion
- 24 Nov 2023 (actual)
- Study completion
- 9 Apr 2024 (actual)
- First posted
- 18 Mar 2020 (actual)
- Results
- Posted 18 Jul 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
PRIMARY OBJECTIVE:
- To estimate the rate of cytomegalovirus (CMV) reactivation in patients treated with letermovir at 3 months after completion of alemtuzumab therapy.
SECONDARY OBJECTIVES:
- To evaluate the tolerability of letermovir in combination with alemtuzumab.
II. To evaluate the efficacy of letermovir for the prevention of clinically significant CMV disease.
III. To estimate the progression free survival of patients in the study population.
IV. To estimate the overall survival of patients in the study population.
EXPLORATORY OBJECTIVE:
- To evaluate mechanisms of antiviral resistance in letermovir prophylaxis failures.
OUTLINE:
Beginning within 7 days of the first administration of standard alemtuzumab, patients receive letermovir orally (PO) (or intravenously [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.
After completion of study treatment, patients are followed up at 30 days.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment (letermovir) | Experimental | Drug: LetermovirBeginning 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (19 listed)
- 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:
- Able to provide informed consent
Key exclusion criteria (36 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| LetermovirAlso: 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, PrevymisGiven PO | Drug | Treatment (letermovir) |
Primary outcome
Cytomegalovirus (CMV) Reactivation
Time frame: During prophylaxis treatment (3 months after last dose of alemtuzumab)
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.
4 secondary outcomes
Number of Participants With Adverse Events Grade 3 or Above
Time frame: Up to 30 days post treatment, an average of 5 months
Development of CMV Disease
Time frame: Up to 2 years
Progression Free Survival (PFS)
Time frame: From trial enrollment to the occurrence of progression and death, assessed up to 2 years
Overall Survival (OS)
Time frame: From trial enrollment to the occurrence of death due to any cause, assessed up to 2 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Feb 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- The JameslineLink provided by the sponsor.
- Individual participant dataSharing planned: No
Related trials for B-Cell Prolymphocytic Leukemia
RecruitingObservational study
Tissue, Blood, and Body Fluid Sample Collection From Patients With Hematologic Cancer
Chronic Myeloproliferative Disorders, Leukemia
Active, not recruitingPhase 1
Cellular Immunotherapy Following Chemotherapy in Treating Patients With Recurrent Non-Hodgkin Lymphomas, Chronic Lymphocytic Leukemia, or B-Cell Prolymphocytic Leukemia
B-Cell Lymphoma, Unclassifiable, With Features Intermediate Between Diffuse Large B-Cell Lymphoma and Classic Hodgkin Lymphoma, B-Cell Prolymphocytic Leukemia
Active, not recruitingObservational study
Infection Prophylaxis and Management in Treating Cytomegalovirus (CMV) Infection in Patients With Hematologic Malignancies Previously Treated With Donor Stem Cell Transplant
Hematopoietic/Lymphoid Cancer, Accelerated Phase Chronic Myelogenous Leukemia
Active, not recruitingPhase 2
HLA-Mismatched Unrelated Donor Peripheral Blood Stem Cell Transplantation With Reduced Dose Post Transplantation Cyclophosphamide GvHD Prophylaxis
Acute Lymphoblastic Leukemia, Acute Myeloid Leukemia
Active, not recruiting
3'-Deoxy-3'-[18F] Fluorothymidine PET Imaging in Patients With Cancer
Brain and Central Nervous System Tumors, Chronic Myeloproliferative Disorders
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
John C Reneau, MD principal investigator
Ohio State University Comprehensive Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Letermovir in people with B-Cell Prolymphocytic Leukemia and Chronic Lymphocytic Leukemia, run by Ohio State University Comprehensive Cancer Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 19 inclusion and 36 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 28 Feb 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 18 Jul 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Cytomegalovirus (CMV) Reactivation (time frame: During prophylaxis treatment (3 months after last dose of alemtuzumab)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Feb 2025.