Actively Recruiting
Nemtabrutinib and Pembrolizumab in Patients With Richter Transformation: A Phase II Study
Led by Roswell Park Cancer Institute · Updated on 2026-05-20
32
Participants Needed
1
Research Sites
52 weeks
Total Duration
On this page
AI-Summary
What this Trial Is About
Researchers are evaluating the combination of nemtabrutinib and pembrolizumab in patients with Richter transformation, diffuse large B-cell lymphoma subtype (RT-DLBCL), a condition arising from chronic lymphocytic leukemia or small lymphocytic lymphoma. This phase II trial aims to measure how well this treatment works by assessing overall response rates and other clinical outcomes, while also studying safety, quality of life, and biological effects on immune cells and tumor characteristics. Participants receive nemtabrutinib orally once daily on days 1 through 21 of each 21-day cycle, along with pembrolizumab given intravenously on day 1 of each cycle. Treatment may continue for up to 35 cycles (about 2 years) unless the disease progresses or side effects become unacceptable. Before and during treatment, patients undergo various scans such as echocardiography or MUGA, PET/CT or CT scans, blood tests, and possibly bone marrow biopsies to monitor their condition and treatment effects. Throughout the study, participants are closely monitored with imaging and laboratory tests to evaluate response and safety. After completing treatment, follow-up visits occur 30 days later and then every 6 months for up to 3 years or until death, totaling up to 5 years of observation. Researchers will measure outcomes including response rates after 6 cycles, survival, duration of response, progression-free survival, and patient-reported quality of life and symptoms.
CONDITIONS
Brief Title
Nemtabrutinib and Pembrolizumab for the Treatment of Richter Transformation, Diffuse Large B-cell Lymphoma Subtype
Who Can Participate
Eligibility Criteria
You may qualify if you...
- Biopsy-proven Richter transformation, diffuse large B-cell lymphoma subtype from chronic lymphocytic leukemia or small lymphocytic lymphoma
- Ineligible for frontline anthracycline-based chemoimmunotherapy or have disease progression after prior RT-DLBCL treatment
- Recovery to grade 1 or baseline from previous treatment adverse events; neuropathy grade 2 or lower allowed
- Measurable disease by imaging or pathology criteria
- Able to swallow and retain oral medication
- Age 18 years or older
- Eastern Cooperative Oncology Group (ECOG) performance status 0-2
- No other malignancy within 2 years except certain low-risk cancers
- Adequate blood counts and organ function as specified
- HIV-positive patients eligible if stable with specific criteria
- Hepatitis B and C patients eligible if viral load undetectable and treated
- Negative pregnancy test and use of birth control for those of childbearing potential
- Ability to understand and sign informed consent
You will not qualify if you...
- Prior therapy with anti-PD-1, anti-PD-L1, or similar immunotherapies
- Recent systemic anti-cancer therapy or radiotherapy within specified timeframes
- Live vaccine within 30 days before treatment
- Immunodeficiency or recent immunosuppressive therapy
- Active progressing malignancy other than allowed exceptions
- Active CNS metastases or carcinomatous meningitis unless stable
- Severe hypersensitivity to pembrolizumab
- Active autoimmune disease requiring recent systemic treatment
- Current or history of pneumonitis or interstitial lung disease requiring steroids
- Active infection needing systemic therapy
- Incomplete recovery from major surgery
- Conditions or treatments interfering with trial participation
- Hodgkin-like Richter's transformation
- Life expectancy less than 1 month
- Uncontrolled serious illnesses
- Concurrent active Hepatitis B and C infections
- Significant ECG abnormalities
- Pregnancy or breastfeeding
- Unwillingness or inability to follow protocol
- Recent investigational agent use
- HIV with Kaposi's sarcoma or Castleman's disease
- Severe bleeding disorders
- Psychiatric or substance abuse disorders interfering with participation
- History of allogeneic tissue or solid organ transplant
- Use of certain medications affecting drug metabolism within 14 days prior to treatment start
AI-Screening
AI-Powered Screening
Complete this quick 3-step screening to check your eligibility
Your Study Journey
Duration - 2 to 4 weeks
Participants are screened for eligibility to participate in the trial.
1 screening visit (in-person)
Duration - Up to 2 years (up to 35 cycles of 21 days each)
Participants receive nemtabrutinib orally once daily on days 1-21 and pembrolizumab intravenously on day 1 of each 21-day cycle. Treatment continues for up to 35 cycles (approximately 2 years) unless disease progresses or there is unacceptable toxicity. Participants undergo PET/CT or CT scans and blood sample collection during the treatment period. Bone marrow biopsies may also be performed as needed.
Visits every 21 days for treatment administration and assessments
Duration - Up to 3 years after treatment completion
After completing treatment, participants are followed up at 30 days and then every 6 months for up to 3 years or until death to monitor health status and quality of life.
1 visit at 30 days post-treatment, then visits every 6 months
Trial Site Locations
Total: 1 location
1
Roswell Park Cancer Institute
Buffalo, New York, United States, 14263
Actively Recruiting
How is the study designed?
Study Type
INTERVENTIONAL
Masking
NONE
Allocation
NA
Model
SINGLE_GROUP
Primary Purpose
TREATMENT
Number of Arms
1
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