RECRUITING

Nemtabrutinib With Rituximab for the Treatment of Patients With Mantle Cell Lymphoma

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

This phase II trial tests how well nemtabrutinib works with rituximab for the treatment of patients with mantle cell lymphoma. Nemtabrutinib is in a class of medications called kinase inhibitors. It blocks a protein called BTK, which is present on B-cell (a type of white blood cells) cancers such as mantel cell lymphoma at abnormal levels. This may help keep cancer cells from growing and spreading. Rituximab is a monoclonal antibody. It binds to a protein called CD20, which is found on B cells (a type of white blood cell) and some types of cancer cells. This may help the immune system kill cancer cells. Giving nemtabrutinib with rituximab may kill more cancer cells in patients with mantle cell lymphoma.

Official Title

A Phase 2 Study of BTK Inhibitor Nemtabrutinib in Combination With Rituximab in Patients With Previously Untreated Mantle Cell Lymphoma

Quick Facts

Study Start:2025-02-11

Study Completion:2027-01-08

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT06572618

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
* Documented informed consent of the participant and/or legally authorized representative. * Assent, when appropriate, will be obtained per institutional guidelines * Age: ≥ 18 years * Eastern Cooperative Oncology Group (ECOG) ≤ 2 * Diagnosis of MCL established by histologic assessment including one of the following: * Immunohistochemistry of the biopsy * Flow cytometry of the biopsy * Requiring treatment for MCL, and for which no prior systemic anticancer therapies have been received * Local radiotherapy not exceeding a total dose of 20 gray (Gy) at least 2 weeks prior the first dose of study therapy is allowed * Laboratory, radiographic, physical exam findings and/or symptoms attributable to MCL. * Asymptomatic patients with blastoid or pleomorphic variant can be enrolled * Radiographically measurable lymphadenopathy or extranodal lymphoid malignancy (as defined by Lugano Classification for non hodgkin's lymphoma \[NHL\]) * Without bone marrow involvement: absolute neutrophil count (ANC) ≥ 1,000/mm\^3, with bone marrow involvement: ANC ≥ 500/mm\^3 * NOTE: Growth factor is not permitted within 7 days of ANC assessment unless cytopenia is secondary to disease involvement * Without bone marrow involvement: platelets ≥ 75,000/mm\^3 with bone marrow involvement: platelets ≥ 30,000/mm\^3 * NOTE: Platelet transfusions are not permitted within 7 days of platelet assessment unless cytopenia is secondary to disease involvement * Total bilirubin ≤ 1.5 × upper limit of normal (ULN) OR direct bilirubin ≤ ULN for participants with total bilirubin levels \> 1.5 × ULN * Aspartate aminotransferase (AST) ≤ 2.5 x ULN * Alanine aminotransferase (ALT) ≤ 2.5 x ULN * Serum creatinine ≤ 1.5 × ULN OR creatinine clearance of ≥ 30 mL/min per 24 hour urine test or the Cockcroft-Gault formula * If not receiving anticoagulants: International normalized ratio (INR) OR prothrombin time (PT) ≤ 1.5 × ULN, if on anticoagulant therapy: PT must be within therapeutic range of intended use of anticoagulants * If not receiving anticoagulants: activated partial thromboplastin time (aPTT) ≤ 1.5 × ULN, if on anticoagulant therapy: aPTT must be within therapeutic range of intended use of anticoagulants * Seronegative for hepatitis C virus (HCV), hepatitis B virus (HBV) (surface antigen negative) OR * If seropositive for HBV or HCV, nucleic acid quantitation must be performed. Viral load must be undetectable. Patients with occult or prior HBV infection (defined as negative hepatitis B surface antigen \[HBsAg\] and positive hepatitis B core antibody \[HBcAb\]) may be included if HBV deoxyribonucleic acid (DNA) is undetectable, if they are willing to undergo DNA testing on day 1 of every cycle and every three months for at least 12 months after the last cycle of study treatment * Participants with HIV are eligible if they meet ALL the following: * CD4 count \> 350 cells/uL at screening * The HIV viral load is below the detectable level as per locally available testing * Are on a stable antiretroviral therapy (ART) regimen for at least 4 weeks prior to study entry * NOTE: ART includes drugs, which are NOT strong CYP3A4 inducers (participants receiving ART that are strong CYP3A4 inducers are not eligible to be included in the study). * HIV screening tests are not required unless: * Known history of HIV infection * As mandated by local health authority * Are compliant with their ART NOTE: If the participant has had an AIDS defining opportunistic infection in the past 12 months prior to screening, they are not eligible to be included in the study * Person of childbearing potential (POCBP): negative urine or serum pregnancy test. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required * Participants assigned male sex at birth: * Nemtabrutinib: 12 days * Rituximab: 3 months * Abstains from penile-vaginal intercourse as their preferred and usual lifestyle (abstinent on a long-term and persistent basis) and agrees to remain abstinent OR * Uses contraception as detailed below unless confirmed to be azoospermic (vasectomized or secondary to medical cause, documented from the site personnel's review of the participant's medical records, medical examination, or medical history interview) as detailed below: * Uses a penile/external condom plus nonparticipant of childbearing potential who is not currently pregnant and should also be advised of the benefit for that partner to use an additional method of contraception, as a condom may break or leak. * Note: Participants capable of producing ejaculate whose partner is pregnant or breastfeeding must agree to use penile/external condom during each episode of sexual activity in which the partner is at risk of drug exposure via ejaculate. * Contraceptive use by participants capable of producing sperm should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. If the contraception requirements in the local label for any of the study interventions are more stringent than the requirements above, the local label requirements are to be followed * Participants assigned female sex at birth: * Is not a person of childbearing potential (POCBP) OR * Is a POCBP and: * Uses a contraceptive method that is highly effective (with a failure rate of \< 1% per year), with low user dependency, or is abstinent from penile-vaginal intercourse as their preferred and usual lifestyle (abstinent on a long-term and persistent basis), during the intervention period and for at least the time needed to eliminate each study intervention after the last dose of study intervention. The length of time required to continue contraception for each study intervention is: * Nemtabrutinib: 1 month * Rituximab: 12 months * The investigator should evaluate the potential for contraceptive method failure (ie, noncompliance, recently initiated) in relationship to the first dose of study intervention. Contraceptive use by POCBPs should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. If the contraception requirements in the local label for any of the study interventions are more stringent than the requirements above, the local label requirements are to be followed. * Has a negative highly sensitive pregnancy test (urine or serum) as required by local regulations within 24 hours (for urine test) or 72 hours (for serum test) before the first dose of study intervention. If a urine test cannot be confirmed as negative (e.g., an ambiguous result), a serum pregnancy test is required. In such cases, the participant must be excluded from participation if the serum pregnancy result is positive. * Abstains from breastfeeding during the study intervention period and for at least 30 days after study intervention with nemtabrutinib. * Medical history, menstrual history, and recent sexual activity has been reviewed by the investigator to decrease the risk for inclusion of a POCBP with an early undetected pregnancy	* Chronic systemic corticosteroid use \> 20 mg/day of prednisone or equivalent. Patients who received corticosteroid treatment with ≤ 20 mg/day of prednisone or equivalent must be documented to be on a stable dose of at least 4 weeks' duration prior to day 1 of cycle 1. Patients may have received a brief (≤ 14 days) course of systemic steroids (≤ 100 mg prednisone equivalent per day) prior to initiation of study therapy for control of lymphoma-related symptoms * History of severe bleeding disorder defined as an ongoing congenital or acquired condition that leads to an increased likelihood of bleeding * Unstable cardiac disease as defined by one of the following: * Acute myocardial infarction (MI) within the past 6 months * NYHA (New York Heart Association) heart failure class III-IV * Unstable angina (angina symptoms at rest) or new-onset angina (begun within the last 3 months) * Corrected QT (QTc) prolongation (defined as a Fridericia's corrected QT interval \[QTcF\] \> 450 msecs) or other significant electrocardiogram (ECG) abnormalities including second degree atrioventricular (AV) block type II, third degree AV block, or bradycardia (ventricular rate less than 50 beats/min) * Positive for hepatitis C virus (HCV) virus by polymerase chain raction (PCR) at screening. Testing only required if the hepatitis (hep) C antibody is positive * AIDS-defining opportunistic infection in the past 12 months prior to screening * Known allergy/sensitivity (≥ grade 3) to nemtabrutinib or any of the excipients; history of allergic reactions attributed to compounds of similar chemical or biologic composition to study agents * Clinically significant uncontrolled illness * Known active bacterial, viral, fungal, mycobacterial, parasitic, or other infection (excluding fungal infections of nail beds) at study enrollment or any major episode of infection (as evaluated by the investigator) within 4 weeks prior to the first study treatment * Primary or secondary central nervous system (CNS) lymphoma at the time of recruitment or history of CNS lymphoma * Other active malignancy. Exceptions include malignancy treated with curative intent and no known active disease present for ≥ 2 years prior to initiation of protocol therapy; adequately treated non-melanoma skin cancer or lentigo maligna (melanoma in situ) without evidence of disease; adequately treated in situ carcinomas (e.g., cervical, esophageal, etc.) without evidence of disease; asymptomatic prostate cancer managed with "watch and wait" strategy * POCBP: Pregnant or breastfeeding * Patients with gastrointestinal dysfunction and/or clinically significant medical condition of malabsorption, inflammatory bowel disease, chronic conditions which manifest with diarrhea, refractory nausea, vomiting or any other condition that will interfere significantly with drug absorption (e.g., gastric bypass surgery, gastrectomy) * Any other condition that would, in the investigator's judgment, contraindicate the patient's participation in the clinical study due to safety concerns with clinical study procedures * Prospective participants who, in the opinion of the investigator, may not be able to comply with all study procedures (including compliance issues related to feasibility/logistics)

Inclusion Criteria

Exclusion Criteria

* Documented informed consent of the participant and/or legally authorized representative.
* Assent, when appropriate, will be obtained per institutional guidelines
* Age: ≥ 18 years
* Eastern Cooperative Oncology Group (ECOG) ≤ 2
* Diagnosis of MCL established by histologic assessment including one of the following:
* Immunohistochemistry of the biopsy
* Flow cytometry of the biopsy
* Requiring treatment for MCL, and for which no prior systemic anticancer therapies have been received
* Local radiotherapy not exceeding a total dose of 20 gray (Gy) at least 2 weeks prior the first dose of study therapy is allowed
* Laboratory, radiographic, physical exam findings and/or symptoms attributable to MCL.
* Asymptomatic patients with blastoid or pleomorphic variant can be enrolled
* Radiographically measurable lymphadenopathy or extranodal lymphoid malignancy (as defined by Lugano Classification for non hodgkin's lymphoma \[NHL\])
* Without bone marrow involvement: absolute neutrophil count (ANC) ≥ 1,000/mm\^3, with bone marrow involvement: ANC ≥ 500/mm\^3
* NOTE: Growth factor is not permitted within 7 days of ANC assessment unless cytopenia is secondary to disease involvement
* Without bone marrow involvement: platelets ≥ 75,000/mm\^3 with bone marrow involvement: platelets ≥ 30,000/mm\^3
* NOTE: Platelet transfusions are not permitted within 7 days of platelet assessment unless cytopenia is secondary to disease involvement
* Total bilirubin ≤ 1.5 × upper limit of normal (ULN) OR direct bilirubin ≤ ULN for participants with total bilirubin levels \> 1.5 × ULN
* Aspartate aminotransferase (AST) ≤ 2.5 x ULN
* Alanine aminotransferase (ALT) ≤ 2.5 x ULN
* Serum creatinine ≤ 1.5 × ULN OR creatinine clearance of ≥ 30 mL/min per 24 hour urine test or the Cockcroft-Gault formula
* If not receiving anticoagulants: International normalized ratio (INR) OR prothrombin time (PT) ≤ 1.5 × ULN, if on anticoagulant therapy: PT must be within therapeutic range of intended use of anticoagulants
* If not receiving anticoagulants: activated partial thromboplastin time (aPTT) ≤ 1.5 × ULN, if on anticoagulant therapy: aPTT must be within therapeutic range of intended use of anticoagulants
* Seronegative for hepatitis C virus (HCV), hepatitis B virus (HBV) (surface antigen negative) OR
* If seropositive for HBV or HCV, nucleic acid quantitation must be performed. Viral load must be undetectable. Patients with occult or prior HBV infection (defined as negative hepatitis B surface antigen \[HBsAg\] and positive hepatitis B core antibody \[HBcAb\]) may be included if HBV deoxyribonucleic acid (DNA) is undetectable, if they are willing to undergo DNA testing on day 1 of every cycle and every three months for at least 12 months after the last cycle of study treatment
* Participants with HIV are eligible if they meet ALL the following:
* CD4 count \> 350 cells/uL at screening
* The HIV viral load is below the detectable level as per locally available testing
* Are on a stable antiretroviral therapy (ART) regimen for at least 4 weeks prior to study entry
* NOTE: ART includes drugs, which are NOT strong CYP3A4 inducers (participants receiving ART that are strong CYP3A4 inducers are not eligible to be included in the study).
* HIV screening tests are not required unless:
* Known history of HIV infection
* As mandated by local health authority
* Are compliant with their ART NOTE: If the participant has had an AIDS defining opportunistic infection in the past 12 months prior to screening, they are not eligible to be included in the study
* Person of childbearing potential (POCBP): negative urine or serum pregnancy test. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
* Participants assigned male sex at birth:
* Nemtabrutinib: 12 days
* Rituximab: 3 months
* Abstains from penile-vaginal intercourse as their preferred and usual lifestyle (abstinent on a long-term and persistent basis) and agrees to remain abstinent OR
* Uses contraception as detailed below unless confirmed to be azoospermic (vasectomized or secondary to medical cause, documented from the site personnel's review of the participant's medical records, medical examination, or medical history interview) as detailed below:
* Uses a penile/external condom plus nonparticipant of childbearing potential who is not currently pregnant and should also be advised of the benefit for that partner to use an additional method of contraception, as a condom may break or leak.
* Note: Participants capable of producing ejaculate whose partner is pregnant or breastfeeding must agree to use penile/external condom during each episode of sexual activity in which the partner is at risk of drug exposure via ejaculate.
* Contraceptive use by participants capable of producing sperm should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. If the contraception requirements in the local label for any of the study interventions are more stringent than the requirements above, the local label requirements are to be followed
* Participants assigned female sex at birth:
* Is not a person of childbearing potential (POCBP) OR
* Is a POCBP and:
* Uses a contraceptive method that is highly effective (with a failure rate of \< 1% per year), with low user dependency, or is abstinent from penile-vaginal intercourse as their preferred and usual lifestyle (abstinent on a long-term and persistent basis), during the intervention period and for at least the time needed to eliminate each study intervention after the last dose of study intervention. The length of time required to continue contraception for each study intervention is:
* Nemtabrutinib: 1 month
* Rituximab: 12 months
* The investigator should evaluate the potential for contraceptive method failure (ie, noncompliance, recently initiated) in relationship to the first dose of study intervention. Contraceptive use by POCBPs should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. If the contraception requirements in the local label for any of the study interventions are more stringent than the requirements above, the local label requirements are to be followed.
* Has a negative highly sensitive pregnancy test (urine or serum) as required by local regulations within 24 hours (for urine test) or 72 hours (for serum test) before the first dose of study intervention. If a urine test cannot be confirmed as negative (e.g., an ambiguous result), a serum pregnancy test is required. In such cases, the participant must be excluded from participation if the serum pregnancy result is positive.
* Abstains from breastfeeding during the study intervention period and for at least 30 days after study intervention with nemtabrutinib.
* Medical history, menstrual history, and recent sexual activity has been reviewed by the investigator to decrease the risk for inclusion of a POCBP with an early undetected pregnancy

* Chronic systemic corticosteroid use \> 20 mg/day of prednisone or equivalent. Patients who received corticosteroid treatment with ≤ 20 mg/day of prednisone or equivalent must be documented to be on a stable dose of at least 4 weeks' duration prior to day 1 of cycle 1. Patients may have received a brief (≤ 14 days) course of systemic steroids (≤ 100 mg prednisone equivalent per day) prior to initiation of study therapy for control of lymphoma-related symptoms
* History of severe bleeding disorder defined as an ongoing congenital or acquired condition that leads to an increased likelihood of bleeding
* Unstable cardiac disease as defined by one of the following:
* Acute myocardial infarction (MI) within the past 6 months
* NYHA (New York Heart Association) heart failure class III-IV
* Unstable angina (angina symptoms at rest) or new-onset angina (begun within the last 3 months)
* Corrected QT (QTc) prolongation (defined as a Fridericia's corrected QT interval \[QTcF\] \> 450 msecs) or other significant electrocardiogram (ECG) abnormalities including second degree atrioventricular (AV) block type II, third degree AV block, or bradycardia (ventricular rate less than 50 beats/min)
* Positive for hepatitis C virus (HCV) virus by polymerase chain raction (PCR) at screening. Testing only required if the hepatitis (hep) C antibody is positive
* AIDS-defining opportunistic infection in the past 12 months prior to screening
* Known allergy/sensitivity (≥ grade 3) to nemtabrutinib or any of the excipients; history of allergic reactions attributed to compounds of similar chemical or biologic composition to study agents
* Clinically significant uncontrolled illness
* Known active bacterial, viral, fungal, mycobacterial, parasitic, or other infection (excluding fungal infections of nail beds) at study enrollment or any major episode of infection (as evaluated by the investigator) within 4 weeks prior to the first study treatment
* Primary or secondary central nervous system (CNS) lymphoma at the time of recruitment or history of CNS lymphoma
* Other active malignancy. Exceptions include malignancy treated with curative intent and no known active disease present for ≥ 2 years prior to initiation of protocol therapy; adequately treated non-melanoma skin cancer or lentigo maligna (melanoma in situ) without evidence of disease; adequately treated in situ carcinomas (e.g., cervical, esophageal, etc.) without evidence of disease; asymptomatic prostate cancer managed with "watch and wait" strategy
* POCBP: Pregnant or breastfeeding
* Patients with gastrointestinal dysfunction and/or clinically significant medical condition of malabsorption, inflammatory bowel disease, chronic conditions which manifest with diarrhea, refractory nausea, vomiting or any other condition that will interfere significantly with drug absorption (e.g., gastric bypass surgery, gastrectomy)
* Any other condition that would, in the investigator's judgment, contraindicate the patient's participation in the clinical study due to safety concerns with clinical study procedures
* Prospective participants who, in the opinion of the investigator, may not be able to comply with all study procedures (including compliance issues related to feasibility/logistics)

Contacts and Locations

Principal Investigator

Alexey V Danilov

PRINCIPAL_INVESTIGATOR

City of Hope Medical Center

Study Locations (Sites)

City of Hope Medical Center

Duarte, California, 91010

United States

City of Hope at Irvine Lennar

Irvine, California, 92618

United States

Collaborators and Investigators

Sponsor: City of Hope Medical Center

Alexey V Danilov, PRINCIPAL_INVESTIGATOR, City of Hope Medical Center

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2025-02-11

Study Completion Date2027-01-08

Study Record Updates

Study Start Date2025-02-11

Study Completion Date2027-01-08

Terms related to this study

Additional Relevant MeSH Terms

Mantle Cell Lymphoma