Trial Title:
Pirtobrutinib and Venetoclax With MRD Detection for Previously Untreated Chronic Lymphocytic Leukemia
NCT ID:
NCT05677919
Condition:
Chronic Lymphocytic Leukemia
Small Lymphocytic Lymphoma
Conditions: Official terms:
Leukemia
Leukemia, Lymphoid
Leukemia, Lymphocytic, Chronic, B-Cell
Venetoclax
Pirtobrutinib
Pyrazole
Study type:
Interventional
Study phase:
Phase 2
Overall status:
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 collection of blood, tissue, stool, and saliva samples
Arm group label:
Treatment (pirtobrutinib and venetoclax)
Other name:
Biological Sample Collection
Other name:
Biospecimen Collected
Other name:
Specimen Collection
Intervention type:
Procedure
Intervention name:
Bone Marrow Aspiration
Description:
Undergo bone marrow aspiration
Arm group label:
Treatment (pirtobrutinib and venetoclax)
Intervention type:
Procedure
Intervention name:
Bone Marrow Biopsy
Description:
Undergo bone marrow biopsy
Arm group label:
Treatment (pirtobrutinib and venetoclax)
Other name:
Biopsy of Bone Marrow
Other name:
Biopsy, Bone Marrow
Intervention type:
Procedure
Intervention name:
Computed Tomography
Description:
Undergo CT scan
Arm group label:
Treatment (pirtobrutinib and venetoclax)
Other name:
CAT
Other name:
CAT Scan
Other name:
Computed Axial Tomography
Other name:
Computerized Axial Tomography
Other name:
Computerized Tomography
Other name:
CT
Other name:
CT Scan
Other name:
tomography
Other name:
Computerized axial tomography (procedure)
Intervention type:
Procedure
Intervention name:
Magnetic Resonance Imaging
Description:
Undergo MRI scan
Arm group label:
Treatment (pirtobrutinib and venetoclax)
Other name:
Magnetic Resonance
Other name:
Magnetic Resonance Imaging Scan
Other name:
Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance
Other name:
MR
Other name:
MR Imaging
Other name:
MRI
Other name:
MRI Scan
Other name:
NMR Imaging
Other name:
NMRI
Other name:
Nuclear Magnetic Resonance Imaging
Other name:
Magnetic resonance imaging (procedure)
Intervention type:
Drug
Intervention name:
Pirtobrutinib
Description:
Given PO
Arm group label:
Treatment (pirtobrutinib and venetoclax)
Other name:
5-Amino-3-(4-((5-fluoro-2-methoxybenzamido)methyl)phenyl)-1-((2S)-1,1,1-trifluoropropan-2-yl)-1h-pyrazole-4-carboxamide
Other name:
BTK Inhibitor LOXO-305
Other name:
LOXO 305
Other name:
LOXO-305
Other name:
LOXO305
Other name:
LY3527727
Other name:
Jaypirca
Intervention type:
Procedure
Intervention name:
Positron Emission Tomography
Description:
Undergo PET scan
Arm group label:
Treatment (pirtobrutinib and venetoclax)
Other name:
Medical Imaging, Positron Emission Tomography
Other name:
PET
Other name:
PET Scan
Other name:
Positron Emission Tomography Scan
Other name:
Positron-Emission Tomography
Other name:
proton magnetic resonance spectroscopic imaging
Other name:
PT
Other name:
Positron emission tomography (procedure)
Intervention type:
Drug
Intervention name:
Venetoclax
Description:
Given PO
Arm group label:
Treatment (pirtobrutinib and venetoclax)
Other name:
ABT-0199
Other name:
ABT-199
Other name:
ABT199
Other name:
GDC-0199
Other name:
RG7601
Other name:
Venclexta
Other name:
Venclyxto
Intervention type:
Procedure
Intervention name:
Echocardiography
Description:
Undergo ECHO
Arm group label:
Treatment (pirtobrutinib and venetoclax)
Other name:
EC
Other name:
ECHO
Intervention type:
Procedure
Intervention name:
Multigated Acquisition Scan
Description:
Undergo MUGA
Arm group label:
Treatment (pirtobrutinib and venetoclax)
Other name:
Blood Pool Scan
Other name:
Equilibrium Radionuclide Angiography
Other name:
Gated Blood Pool Imaging
Other name:
Gated Heart Pool Scan
Other name:
MUGA
Other name:
MUGA Scan
Other name:
Multi-Gated Acquisition Scan
Other name:
Radionuclide Ventriculogram Scan
Other name:
Radionuclide ventriculography
Other name:
RNVG
Other name:
SYMA Scanning
Other name:
Synchronized Multigated Acquisition Scanning
Summary:
This phase II trial studies how well pirtobrutinib and venetoclax work in treating
patients with chronic lymphocytic leukemia or small lymphocytic lymphoma. This study also
seeks to adopt a blood test which shows a small number of cancer cells in the body after
cancer treatment called minimal residual disease as a guide to determine length of
treatment. Drugs used in chemotherapy, such as pirtobrutinib and venetoclax, work in
different ways to stop the growth of tumor cells, either by killing the cells or by
stopping them from dividing. Identifying minimal residual disease results after
combination chemotherapy may help guide future treatment decisions for patients with
chronic lymphocytic leukemia or small lymphocytic lymphoma.
Detailed description:
PRIMARY OBJECTIVE:
I. To assess the rate of undetectable minimal residual disease (MRD) (uMRD, by ClonoSEQ)
in both peripheral blood and bone marrow after 15 cycles of treatment.
SECONDARY OBJECTIVES:
I. To assess best peripheral blood uMRD rate and best bone marrow uMRD rate by ClonoSEQ.
II. To assess progression-free survival (PFS). III. To assess overall response rate (ORR)
and complete response (CR) rate. IV. To assess duration of response (DOR), time to next
treatment (TTNT), and overall survival (OS).
V. To assess toxicities associated with pirtobrutinib and venetoclax.
CORRELATIVE RESEARCH OBJECTIVE:
I. To analyze the dynamics of MRD (by ClonoSEQ) and its association with response to
treatment and clinical outcomes.
OUTLINE:
Patients receive pirtobrutinib orally (PO) daily (QD) on days 1-28 of each cycle and
venetoclax PO QD starting in cycle 4 on days 1-28 of each cycle. Treatment repeats every
28 days for up to 27 cycles in the absence of disease progression or unacceptable
toxicity. Patients also undergo computed tomography (CT), magnetic resonance imaging
(MRI), and/or positron emission tomography (PET)/CT scans during screening and on study.
Patients also undergo bone marrow aspiration and biopsy and collection of blood samples
throughout the study and collection of stool and saliva on study. Patients may undergo
echocardiography (ECHO) or multigated acquisition (MUGA) scan during screening.
After completion of study treatment, patients follow up at 30 days and every 6 months for
up to 3 years for clinical follow-up and then every 6 months for up to 5 years after
registration for survival follow-up.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- PRE-REGISTRATION - INCLUSION CRITERIA
- Age >= 18 years.
- Confirmed diagnosis of CLL according to the International Workshop on (iw)CLL 2018
criteria or biopsy proven small lymphocytic lymphoma (SLL) according to the World
Health Organization (WHO) criteria.
- NOTE: The diagnosis of CLL requires the presence of > 5 × 10^9/L B lymphocytes
in the peripheral blood. Typically, CLL cells express CD19, CD5, and CD23, with
variable expression of CD20 (typically dim), and show kappa or lambda light
chain restriction.
- NOTE: A diagnosis of mantle cell lymphoma must be excluded by demonstrating a
negative cyclin D1 expression and/or a negative t(11;14) translocation.
- No prior CLL/SLL-directed therapy such as chemotherapy, immunotherapy, targeted
therapy with small molecule inhibitors, radiation therapy, or cellular therapy.
- NOTE: Nutraceutical treatments with no established benefit in CLL (such as
epigallocatechin gallate or EGCG, found in green tea or other herbal treatments
or supplemental vitamins) will not be considered prior CLL/SLL-directed
therapy.
- NOTE: Prior corticosteroid therapy for an indication other than CLL/SLL will
not be considered prior CLL/SLL-directed therapy.
- NOTE: A short course of corticosteroid (e.g., =< 1 week of intravenous or =< 2
weeks of oral corticosteroid) given for acute SLL-related symptoms or impending
severe organ dysfunction is allowed.
- Provide written informed consent.
- REGISTRATION - INCLUSION CRITERIA
- Patients with SLL must have a measurable B-cell clone (of CLL immunophenotype) in
either peripheral blood or bone marrow (e.g., by flow cytometry) at baseline.
- Meeting at least one of the following indications for treatment:
- Evidence of progressive marrow failure as manifested by the development of, or
worsening of, anemia (Hb < 11 g/dL) and/or thrombocytopenia (platelet counts <
100 × 10^9/L).
- Massive (i.e., >= 6 cm below the left costal margin) or progressive or
symptomatic splenomegaly.
- Massive nodes (i.e., >= 10 cm in longest diameter) or progressive or
symptomatic lymphadenopathy.
- Progressive lymphocytosis with an increase of >= 50% over a 2-month period, or
lymphocyte doubling time (LDT) < 6 months. LDT can be obtained by linear
regression extrapolation of absolute lymphocyte counts obtained at intervals of
2 weeks over an observation period of 2 to 3 months; patients with initial
blood lymphocyte counts < 30 × 10^9/L may require a longer observation period
to determine the LDT. Factors contributing to lymphocytosis other than CLL
(e.g., infections, steroid administration) should be excluded.
- Autoimmune complications including anemia or thrombocytopenia poorly responsive
to corticosteroids.
- Symptomatic or functional extranodal involvement (e.g., skin, kidney, lung,
spine).
- Disease-related symptoms as defined by any of the following:
- Unintentional weight loss >= 10% within the previous 6 months.
- Significant fatigue (i.e., cannot work or unable to perform usual activities).
- Fevers >= 100.4°F or 38.0°C for 2 or more weeks without evidence of infection.
- Night sweats for >= 1 month without evidence of infection.
- Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0, 1 or 2
- Absolute neutrophil count (ANC) >= 0.75 × 10^9/L (750/mm^3) (obtained =< 14 days
prior to registration)
- Platelet count >= 50 × 10^9/L (obtained =< 14 days prior to registration)
- Hemoglobin >= 8 g/dL (obtained =< 14 days prior to registration)
- Activated partial thromboplastin time (aPTT) or partial thromboplastin time (PTT)
and prothrombin (PT) or international normalized ratio (INR) =< 1.5 × upper normal
limit (ULN) (obtained =< 14 days prior to registration)
- Total bilirubin =< 1.5 × ULN (or =< 3 × ULN if there is evidence of parenchymal
liver involvement with CLL/SLL); patients with hemolysis or Gilbert's disease may
enroll if indirect bilirubin is =< 3 × ULN and direct bilirubin is =< 1.5 × ULN
(obtained =< 14 days prior to registration)
- Alanine aminotransferase (ALT) and aspartate transaminase (AST) =< 3 × ULN (or =< 5
× ULN if there is evidence of parenchymal liver involvement with CLL/SLL) (obtained
=< 14 days prior to registration)
- Calculated creatinine clearance >=40 ml/min using the Cockcroft-Gault formula.
- Negative serum pregnancy test done =< 7 days prior to registration, for persons of
childbearing potential only.
- NOTE: Persons of reproductive potential is defined as following: menarche and
who are not postmenopausal (and 2 years of non-therapy-induced amenorrhea) or
surgically sterile.
- Male and females of reproductive potential must agree to use a highly effective
(preferred) or an acceptable form of birth control during study treatment and for 6
months following the last dose of pirtobrutinib.
- Males must be willing to not donate sperm during the study and for 6 months after
the last dose of any study drug.
- Willingness to provide mandatory research blood, bone marrow, saliva, and stool
specimens for correlative research.
- Willing to return to enrolling institution for follow-up (during treatment and
Clinical Follow-up).
Exclusion Criteria:
- REGISTRATION - EXCLUSION CRITERIA
- Any of the following because this study involves an investigational agent whose
genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn are
unknown:
- Pregnant persons.
- Nursing persons (lactating persons are eligible provided that they agree not to
breast feed while receiving treatment on the study or within 6 months of the
last dose of study treatment).
- Male or females of reproductive potential who are unwilling to employ adequate
contraception during treatment and for 6 months after pirtobrutinib.
- Evidence of Richter transformation.
- Central nervous system (CNS) involvement of CLL/SLL (e.g., any parenchymal,
leptomeningeal, cerebrospinal fluid [CSF], cranial or spinal nerve root
involvement).
- Active uncontrolled autoimmune complications (e.g., active autoimmune hemolytic
anemia or clinically significant immune thrombocytopenia).
- Receiving any other investigational agent which would be considered as a treatment
for the CLL/SLL (with the exception of corticosteroid).
- Any of the following medication requirement or recent use:
- Requirement of a strong cytochrome P450 (CYP) 3A inhibitor or inducer during
the study.
- Use of a strong or moderate CYP3A inhibitor or inducer =< 7 days prior to
registration.
- Requirement of a strong P-glycoprotein 1 (PgP) inhibitor during the study.
- Anticoagulation with a vitamin K antagonist =< 7 days prior to registration or
anticipated use during the study.
- Vaccination with live vaccine =< 28 days prior to registration.
- NOTE: Because of their effect on CYP3A4, use of any of the following =< 3
days of study therapy start or planned use during study participation is
prohibited:
- Grapefruit or grapefruit products.
- Seville oranges or products from Seville oranges.
- Star fruit.
- Malabsorption syndrome or other condition that precludes enteral route of
administration.
- History of a bleeding diathesis (e.g., hemophilia, von Willebrand disease, etc.).
- Patients who have tested positive for Human Immunodeficiency Virus (HIV) are
excluded due to potential drug-drug interactions between anti-retroviral medications
and pirtobrutinib and risk of opportunistic infections with both HIV and
irreversible BTK inhibitors. For patients with unknown HIV status, HIV testing will
be performed at Screening and result should be negative for enrollment.
- Co-morbid systemic illnesses or other severe concurrent disease which, in the
judgment of the investigator, would make the patient inappropriate for entry into
this study or interfere significantly with the proper assessment of safety and
toxicity of the prescribed regimens.
- Uncontrolled intercurrent illness including, but not limited to:
- Ongoing or active infection.
- Known active cytomegalovirus (CMV) infection is ineligible; unknown or
negative status are eligible.
- Hepatitis B virus (HBV): Patients with positive hepatitis B surface
antigen (HBsAg) are excluded. Patients with positive hepatitis B core
antibody (anti-HBc) and negative HBsAg require hepatitis B polymerase
chain reaction (PCR) evaluation. Patients who are hepatitis B PCR positive
will be excluded.
- Hepatitis C virus (HCV): If hepatitis C antibody result is positive,
patient will need to have a negative result for hepatitis C ribonucleic
acid (RNA). Patients who are hepatitis C RNA positive will be excluded.
- New York Heart Association (NYHA) Class III or IV or symptomatic congestive
heart failure.
- Documented left ventricular ejection fraction (LVEF) by any method of =< 40% =<
12 months prior to registration.
- Unstable angina or acute coronary syndrome =<3 months prior to registration.
- History of myocardial infarction =< 6 months prior to registration.
- Uncontrolled or symptomatic cardiac arrhythmia.
- NOTE: Patients with pacemakers are eligible if they have no history of
fainting or clinically relevant arrhythmias while using the pacemaker
- Prolongation of the QT interval corrected for heart rate (Fridericia's
correction formula [QTcF]) > 470 msec on at least 2/3 consecutive
electrocardiograms (ECGs), and mean QTcF > 470 msec on all 3 ECGs, during
screening.
- NOTE: QTcF is calculated using Fridericia's Formula (QTcF).
- NOTE: Correction for a widened QRS complex such as pacing, underlying
bundle branch block (BBB), etc. is allowed e.g., "Adjusted QTcF" =
measured QTcF - (measured QRS - 90 ms).
- NOTE: Correction of suspected drug-induced QTcF prolongation can be
attempted at the investigator's discretion and only if clinically safe to
do so with either discontinuation of the offending drug or switch to
another drug not known to be associated with QTcF prolongation.
- History of cerebral vascular accident =< 6 months prior to registration.
- Ongoing inflammatory bowel disease (such as ulcerative colitis) requiring
active treatment.
- Oxygen dependent baseline lung disease (such as interstitial lung disease or
chronic obstructive pulmonary disease [COPD]).
- Psychiatric illness/social situations that would limit compliance with study
requirements.
- Major surgery =< 4 weeks prior to registration.
- Other active primary malignancy (other than localized non-melanotic skin cancer or
carcinoma in situ of the cervix) requiring treatment or limiting expected survival
to =< 2 years.
- NOTE: If there is a history of prior malignancy, the patient must not require
ongoing therapy such as radiation, chemotherapy, or immunotherapy for their
cancer. Patients on hormonal therapy for adequately treated nonmetastatic
breast or prostate cancer are permitted if they meet other eligibility
criteria.
- Have a known hypersensitivity to any of the excipients of pirtobrutinib.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Mayo Clinic in Rochester
Address:
City:
Rochester
Zip:
55905
Country:
United States
Status:
Recruiting
Contact:
Last name:
Clinical Trials Referral Office
Phone:
855-776-0015
Email:
mayocliniccancerstudies@mayo.edu
Investigator:
Last name:
Yucai Wang, M.D., Ph.D.
Email:
Principal Investigator
Investigator:
Last name:
Sameer A. Parikh, M.B.B.S.
Email:
Principal Investigator
Start date:
January 31, 2023
Completion date:
August 31, 2027
Lead sponsor:
Agency:
Mayo Clinic
Agency class:
Other
Source:
Mayo Clinic
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05677919
https://www.mayo.edu/research/clinical-trials
