Trial Title:
Nemtabrutinib With Rituximab for the Treatment of Patients With Mantle Cell Lymphoma
NCT ID:
NCT06572618
Condition:
Mantle Cell Lymphoma
Conditions: Official terms:
Lymphoma
Lymphoma, Mantle-Cell
Rituximab
Antineoplastic Agents, Immunological
Antibodies
Immunoglobulins
Antibodies, Monoclonal
Tyrosine Kinase Inhibitors
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Not yet recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Procedure
Intervention name:
Biospecimen Collection
Description:
Undergo blood sample collection
Arm group label:
Treatment (nemtabrutinib and rituximab)
Other name:
Biological Sample Collection
Other name:
Biospecimen Collected
Other name:
Specimen Collection
Intervention type:
Procedure
Intervention name:
Bone Marrow Biopsy
Description:
Undergo bone marrow biopsy
Arm group label:
Treatment (nemtabrutinib and rituximab)
Other name:
Biopsy of Bone Marrow
Other name:
Biopsy, Bone Marrow
Intervention type:
Drug
Intervention name:
Nemtabrutinib
Description:
Given PO
Arm group label:
Treatment (nemtabrutinib and rituximab)
Other name:
ARQ 531
Other name:
ARQ-531
Other name:
ARQ531
Other name:
Bruton's Tyrosine Kinase Inhibitor ARQ 531
Other name:
BTK Inhibitor ARQ 531
Other name:
MK-1026
Intervention type:
Procedure
Intervention name:
Positron Emission Tomography and Computed Tomography Scan
Description:
Undergo PET-CT scan
Arm group label:
Treatment (nemtabrutinib and rituximab)
Other name:
PET-CT Scan
Other name:
PET/CT SCAN
Other name:
Positron Emission Tomography/Computed Tomography
Intervention type:
Biological
Intervention name:
Rituximab
Description:
Given IV
Arm group label:
Treatment (nemtabrutinib and rituximab)
Other name:
ABP 798
Other name:
BI 695500
Other name:
BI-695500
Other name:
BI695500
Other name:
Blitzima
Other name:
C2B8 Monoclonal Antibody
Other name:
Chimeric Anti-CD20 Antibody
Other name:
CT-P10
Other name:
IDEC 102
Other name:
IDEC-102
Other name:
IDEC-C2B8
Other name:
IDEC-C2B8 Monoclonal Antibody
Other name:
IDEC102
Other name:
Ikgdar
Other name:
Mabtas
Other name:
MabThera
Other name:
Monoclonal Antibody IDEC-C2B8
Other name:
PF 05280586
Other name:
PF-05280586
Other name:
PF05280586
Other name:
Riabni
Other name:
Ritemvia
Other name:
Rituxan
Other name:
Rituximab ABBS
Other name:
Rituximab ARRX
Other name:
Rituximab Biosimilar ABP 798
Other name:
Rituximab Biosimilar BI 695500
Other name:
Rituximab Biosimilar CT-P10
Other name:
Rituximab Biosimilar GB241
Other name:
Rituximab Biosimilar IBI301
Other name:
Rituximab Biosimilar JHL1101
Other name:
Rituximab Biosimilar PF-05280586
Other name:
Rituximab Biosimilar RTXM83
Other name:
Rituximab Biosimilar SAIT101
Other name:
Rituximab Biosimilar SIBP-02
Other name:
rituximab biosimilar TQB2303
Other name:
Rituximab PVVR
Other name:
Rituximab-abbs
Other name:
Rituximab-arrx
Other name:
Rituximab-blit
Other name:
Rituximab-pvvr
Other name:
Rituximab-rite
Other name:
Rituximab-rixa
Other name:
Rituximab-rixi
Other name:
Rixathon
Other name:
Riximyo
Other name:
RTXM 83
Other name:
RTXM-83
Other name:
RTXM83
Other name:
Ruxience
Other name:
Truxima
Summary:
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.
Detailed description:
PRIMARY OBJECITVE:
I. To evaluate the efficacy (complete response rate) of nemtabrutinib and rituximab
(Nem-R) in patients with treatment-naïve mantle cell lymphoma (MCL).
SECONDARY OBJECITVES:
I. To evaluate objective response rate (ORR), median progression-free survival (PFS),
overall survival (OS) and duration of response (DOR).
II. To evaluate safety and tolerability of Nem-R in patients with treatment-naïve MCL.
EXPLORATORY OBJECITVES:
I. To conduct preliminary assessment of the predictive value of minimal residual disease
(MRD) in MCL treated with a novel regimen.
II. To explore immune cell populations in patients treated with Nem-R. III. To explore
mechanisms of resistance to Nem-R therapy in MCL. IV. To estimate the second PFS after
salvage therapy for patients who progress after Nem-R therapy.
OUTLINE:
INDUCTION: Patients receive nemtabrutinib orally (PO) once per day (QD) on days 1-28 of
each cycle and rituximab intravenously (IV) on days 1, 8, 15 and 22 of cycle 1 and on day
1 of subsequent cycles. Cycles repeat every 28 days for up to 6 cycles in the absence of
disease progression or unacceptable toxicity.
MAINTENANCE: Patients receive nemtabrutinib PO QD on days 1-28 of each cycle and
rituximab IV on day 1 of event numbered cycles. Cycles repeat every 28 days for up to 24
cycles in the absence of disease progression or unacceptable toxicity. Patients may
optionally continue to receive nemtabrutinib PO QD in the absence of disease progression
or unacceptable toxicity.
Patients undergo bone marrow biopsy during screening and may undergo throughout the trial
and positron emission tomography-computed tomography (PET-CT) scan and blood sample
collection throughout the study.
After completion of study treatment, patients are followed up at 30 days, then every 3
months for the first 2 years and every 6 months for the third year for patients in
remission at the end of treatment or every 6 months for patients who end response follow
up.
Criteria for eligibility:
Criteria:
Inclusion 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:
If capable of producing sperm, the participant agrees to the following 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: 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:
A participant assigned female sex at birth is eligible to participate if not pregnant or
breastfeeding, and at least one of the following conditions applies:
- 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
Exclusion Criteria:
- 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)
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
City of Hope Medical Center
Address:
City:
Duarte
Zip:
91010
Country:
United States
Contact:
Last name:
Alexey V. Danilov
Phone:
626-218-2405
Email:
adanilov@coh.org
Investigator:
Last name:
Alexey V. Danilov
Email:
Principal Investigator
Facility:
Name:
City of Hope at Irvine Lennar
Address:
City:
Irvine
Zip:
92618
Country:
United States
Contact:
Last name:
Alexey V. Danilov
Phone:
626-218-2405
Email:
adanilov@coh.org
Investigator:
Last name:
Alexey V. Danilov
Email:
Principal Investigator
Start date:
February 11, 2025
Completion date:
February 19, 2026
Lead sponsor:
Agency:
City of Hope Medical Center
Agency class:
Other
Collaborator:
Agency:
National Cancer Institute (NCI)
Agency class:
NIH
Source:
City of Hope Medical Center
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06572618
