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New treatment option for Richter Syndrome
Official title Nemtabrutinib and Pembrolizumab for the Treatment of Richter Transformation, Diffuse Large B-cell Lymphoma Subtype
ClinicalTrials.gov ID: NCT06863402
What this study is testing
What is Nemtabrutinib?
Nemtabrutinib is an investigational medicine, given as an once-daily infusion into a vein, being studied as a potential treatment for richter syndrome.
Also referred to as ARQ 531, ARQ-531.
Plain-language explanation of the investigational treatment - it is being studied and is not an approved or proven therapy. The study team can confirm the details.
- What it's testing
- 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.
- Phase 2: a mid-size study of how well it works
A plain-language read of the study's public ClinicalTrials.gov listing. The study team confirms the details.
Who can take part
Ages 18 and older
You may be able to join if
- Patients with biopsy-proven Richter transformation, diffuse large B-cell lymphoma subtype (RT-DLBCL) from an antecedent or concurrently diagnosed...
- Be ineligible for frontline anthracycline-based chemoimmunotherapy (determined by treating investigator) OR have clinical evidence of disease...
- Participants who have adverse events (AEs) due to previous anti-cancer therapies must have recovered to ≤ grade 1 or baseline. Participants with...
- Note: Participants who have lingering cytopenias from prior anti-cancer therapy or progressive disease may be eligible at the discretion of the study...
- Have measurable disease as determined by imaging (by positron-emission tomography [PET] and/or computed tomography [CT] scans), immunohistochemistry...
You likely can't join if
- 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...
- 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...
- Has received prior radiotherapy within 2 weeks of start of study intervention or has radiation related toxicities requiring corticosteroids. Note...
- Has received a live vaccine or live-attenuated vaccine within 30 days before the first dose of study intervention. Administration of killed or...
- Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (daily dose exceeding 10 mg of prednisone equivalent) or any...
- Known additional malignancy that is progressing or has required active treatment within the past 2 years.
See the full eligibility criteria
Who can join
- 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...
- 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...
- 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...
- Have measurable disease as determined by imaging (by positron-emission tomography [PET] and/or computed tomography [CT] scans), immunohistochemistry, and/or flow cytometry, as per the Cheson criteria.
- Have the ability to swallow and retain oral medication.
- Age 18 years and older on the day of signing informed consent.
- Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.
- Be free from other malignancy within 2 years prior to enrollment (with the exception of CLL/SLL, low-risk and early stage [T1-T2a- Gleason score ≤ 6, and prostate-specific antigen [PSA] \< 10 ng/mL] prostate cancer, or...
- Absolute neutrophil count: ANC ≥ 500 cells/µL (without G-CSF dose within the last 7 days prior to initiation of study treatment
- Platelets: ≥ 25,000/µL -not requiring transfusion within the last 3 days prior to initiation of study treatment). Patients on medications that increase bleeding risk (e.g. systemic anticoagulation, anti-platelet...
- Hemoglobin: ≥ 7gm/dL (transfusion support allowed).
- Total bilirubin: ≤ 1.5 x upper limit of normal (ULN) OR direct bilirubin ≤ ULN for participants with total bilirubin levels \> 1.5 x ULN.
- Aspartate aminotransferase (AST)(serum glutamic-oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT)(serum glutamic-pyruvic transaminase [SGPT]): ≤ 2.5 x ULN (≤ 5 x ULN for participants with liver metastases).
- Creatinine clearance (CrCl): ≥ 30 mL/min (per Cockroft-Gault equation).
- International normalized ratio (INR) (prothrombin [PT]/activated partial thromboplastin time [aPTT]): ≤ 1.5 x ULN, unless participant is receiving anticoagulant therapy, as long as PT or aPTT is within therapeutic range...
- Patients with history of human immunodeficiency virus (HIV) infection are potentially eligible (after conferring with the PI) if they meet ALL of the following criteria:
- Must have a CD4+ T-cell count ≥ 350 cells/mm\^3 AND an HIV viral load below the detectable level as per locally available testing at the time of screening
- It is advised that participants must not have had any AIDS-defining opportunistic infections within the past 12 months.
- Participants on anti-retroviral therapy (ART) must have been on a stable regimen, without changes in drugs or dose modification, for at least 4 weeks before study entry (day 1) and agree to continue ART throughout the...
- The combination ART regimen must not contain any antiretroviral medications that interact with strong CYP3A4 inhibitors/inducers/substrates (\ ). Participants receiving ART that are strong CYP3A4 inducers are not...
- Participants who are hepatitis B surface antigen (HBsAg) positive are eligible if they have received hepatitis B virus (HBV) antiviral therapy for at least 4 weeks and have undetectable HBV viral load prior to...
- Participants with history of hepatitis C virus (HCV) infection are eligible if HCV viral load is undetectable at screening (Participants must have completed curative anti-viral therapy at least 4 weeks prior to the...
- A person of childbearing potential must have a negative urine or serum pregnancy within 72 hours prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a...
- Participants of child-bearing potential must agree to use 2 methods of birth control or be surgically sterile or abstain from heterosexual activity for the course of the study through 6 months after the last dose of...
- Participant must understand the investigational nature of this study and sign an Independent Ethics Committee/Institutional Review Board approved written informed consent form prior to receiving any study related...
What rules you out
- 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...
- 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...
- 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.
- Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (daily dose exceeding 10 mg of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first...
- Known additional malignancy that is progressing or has required active treatment within the past 2 years.
- Has known active CNS metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are radiologically stable, i.e. without evidence of progression for at...
- Has severe hypersensitivity (≥ grade 3) to pembrolizumab and/or any of its excipients.
- Has active autoimmune disease that has required systemic treatment in the past 2 years except replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid allowed).
- Has a history of (non-infectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease.
- Has an active infection requiring systemic therapy.
- Has not adequately recovered from major surgery or has ongoing surgical complications.
- Has a history or current evidence of any condition, therapy, or laboratory abnormality or other circumstance that might confound the results of the study, interfere with the participant's participation for the full...
- Patients with pathologically confirmed Hodgkin-like RT (RT-classical Hodgkin's lymphoma [cHL]).
- Estimated life expectancy of \< 1 month as determined by the treating investigator.
- Uncontrolled active illness including but not limited to heart failure, unstable ischemic heart disease, arrhythmia, psychiatric illness, acute renal failure, and any other conditions that would reasonably be expected...
- Concurrent active Hepatitis B (defined as HBsAg positive and/or detectable HBV deoxyribonucleic acid [DNA]) and Hepatitis C virus (defined as anti-HCV Ab positive and detectable HCV RNA) infection.
- Corrected QT interval (QTc) prolongation (defined as a Fridericia's corrected QT [QTcF] \> 450 msecs) or other significant electrocardiogram (ECG) abnormalities including second degree atrioventricular (AV) block type...
- Is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 120 days after the last dose of trial treatment.
- Unwilling or unable to follow protocol requirements.
- Received any other investigational agent within 30 days prior to enrollment.
- HIV-infected participants with a history of Kaposi's sarcoma and/or multicentric Castleman's disease.
- History of severe bleeding disorder defined as an ongoing congenital or acquired condition that leads to an increased likelihood of bleeding.NOTE: Patients on active anti-coagulation, anti-platelet therapies, and other...
- Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
- Has had an allogeneic tissue/solid organ transplant. Note: Patients with prior allogeneic hematopoietic stem cell transplant or allogeneic cellular therapy are allowed, provided they meet they meet the washout period.
- Use of medications that are strong CYP3A4 inhibitors or inducers or P-gp and/or BCRP substrates with a narrow therapeutic index within 14 days prior to first dose of study treatment or 5 half-lives of the given drug...
The study team makes the final eligibility decision.
Where it's taking place
- Buffalo, New York, United States
Questions & answers
Do participants get paid in this trial?
This listing doesn't specify compensation. Many trials still reimburse travel or offer a stipend, so it's worth asking the study team when you connect.
Is it free to join, and do I need insurance?
Searching and applying through BridgeMD is free. In clinical trials the study-related treatment and visits are generally provided at no cost to you. You usually don't need insurance to take part - confirm specifics with the study team.
How long does this study last?
The listing doesn't state an exact length. The study team walks you through the schedule and number of visits before you decide to enroll.
Who can join this trial?
This study is enrolling all sexes, 18 years and older. The study team makes the final eligibility decision.
Where is this trial taking place?
Study sites include Buffalo, New York, United States. Enter your location above to see the nearest site and check your eligibility.
Explore other conditions
BridgeMD is an information and trial-matching tool - not medical advice, and not the study sponsor. Details come from ClinicalTrials.gov; the study team decides eligibility.