Nemtabrutinib and Pembrolizumab for the Treatment of Richter Transformation, Diffuse Large B-cell Lymphoma Subtype
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age18+
SponsorRoswell Park Cancer Institute
About this trial
This phase II trial tests how well nemtabrutinib in combination with pembrolizumab works in treating patients with Richter transformation, diffuse large B-cell lymphoma subtype (RT-DLBCL). Nemtabrutinib is in a class of medications called kinase inhibitors. It blocks a protein called BTK, which is present on B-cells (a type of white blood cell) in cancers such as Richter transformation at abnormal levels. This may help keep cancer cells from growing and spreading. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of cancer cells to grow and spread. Giving nemtabrutinib in combination with pembrolizumab may kill more cancer cells in patients with RT-DLBCL.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Patients with biopsy-proven Richter transformation, diffuse large B-cell lymphoma subtype (RT-DLBCL) from an antecedent or concurrently diagnosed chronic lymphocytic leukemia (CLL) and/or small lymphocytic lymphoma (SLL).
Be ineligible for frontline anthracycline-based chemoimmunotherapy (determined by treating investigator) OR have clinical evidence of disease progression after any prior treatment for RT-DLBCL.
Participants who have adverse events (AEs) due to previous anti-cancer therapies must have recovered to ≤ grade 1 or baseline. Participants with endocrine-related AEs who are adequately treated with hormone replacement or participants who have ≤ grade 2 neuropathy are eligible.
Note: Participants who have lingering cytopenias from prior anti-cancer therapy or progressive disease may be eligible at the discretion of the study principal investigator (PI), provided they meet all other study criteria.
Disqualifiers
Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PDL2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g., CTLA-4, OX40, CD137).
Has received prior systemic anti-cancer therapy within 5 half-lives or 14 days, whichever is lesser (or within 30 days for cellular therapy or investigational agents, or within 100 days post allogeneic hematopoietic stem cell transplantation and without any grade ≥ 2 graft versus host disease) prior to enrollment.
Has received prior radiotherapy within 2 weeks of start of study intervention or has radiation related toxicities requiring corticosteroids. Note: Two weeks or fewer of palliative radiotherapy for non-central nervous system (CNS) disease is permitted. The last radiotherapy treatment must have been performed at least 7 days before the first dose of study intervention.
Has received a live vaccine or live-attenuated vaccine within 30 days before the first dose of study intervention. Administration of killed or messenger ribonucleic acid (mRNA) vaccines is allowed.
Trial design
Design model
Single group
Treatments tested in this trial
Biospecimen Collection
Procedure/SurgeryUndergo blood sample collection
Bone Marrow Biopsy
Procedure/SurgeryUndergo bone marrow biopsy
Computed Tomography
Procedure/SurgeryUndergo PET/CT or CT
Echocardiography
Procedure/SurgeryUndergo ECHO
Multigated Acquisition Scan
Procedure/SurgeryUndergo MUGA
Nemtabrutinib
DrugGiven PO
Pembrolizumab
Biological/VaccineGiven IV
Positron Emission Tomography
Procedure/SurgeryUndergo PET/CT
Questionnaire Administration
Other interventionAncillary studies
Treatment groups
32 Participants
are divided into 1 treatment groupGroup A: Treatment (nemtabrutinib, pembrolizumab)Experimental treatment 9 interventions
Trial outcomes
Primary outcomes
1
Overall response rate
Will be defined as having either a complete response (CR) or partial response (PR) as per Cheson et al., 2014. Will be summarized using frequencies and relative frequencies.
Time frame
After 6 cycles (approximately 18 weeks) (1 cycle = 21 days)2
Quality of life
Tolerability and patient-reported outcomes (PROs) assessed using the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (version 3) . EORTC-C 30 is measure from nat at all (better) to very much (worse)
Time frame
Up to 3 years after completion of study treatment3
Quality of life -PRO CTCAE
Will be evaluated using the patient reported outcome PRO CTCAE measurement system. Responses are scored on a 0-5 point scale where higher outcomes indicate worse
Time frame
Up to 3 years after completion of study treatmentSecondary outcomes
1
Response outcomes
CR, PR, stable disease (SD), CR+PR, and CR+PR+SD will be summarized using frequencies and relative frequencies, with response rates estimated using 90% credible regions obtained by Jeffrey's prior method.
Time frame
Up to 3 years after completion of study treatment2
Duration of response
Will be summarized using standard Kaplan-Meier methods, where the median will be estimated with a 90% confidence interval.
Time frame
From first PR (or greater) until disease progression or last follow-up, assessed up to 3 years after completion of study treatment3
Overall survival
Will be summarized using standard Kaplan-Meier methods, where the medians will be estimated with 90% confidence intervals.
Time frame
From treatment initiation until death due to any cause or last follow-up, assessed up to 3 years after completion of study treatment4
Progression-free survival
Will be summarized using standard Kaplan-Meier methods, where the medians will be estimated with 90% confidence intervals.
Time frame
From treatment initiation until disease progression, death due to any cause, subsequent treatment, or last follow-up, assessed up to 3 yearsSponsors and contacts
Click on the lead sponsor to view all of their trials.
Source ClinicalTrials.gov