| Eligibility |
Inclusion Criteria:
1. Subject must be = 18 years of age.
2. Subject must have a confirmed Mantle Cell Lymphoma (MCL) diagnosis according to WHO
(2008) criteria.
3. Previously untreated MCL
4. Subject has an Eastern Cooperative Oncology Group (ECOG) performance score of = 2.
5. Nonsterile men and women of child-bearing potential must agree to use highly effective
contraceptives (e.g., condoms, implants, injectables, combined oral contraceptives,
intrauterine devices, sexual abstinence, or sterilized partner) while on study; this
should be maintained for 90 days after the last dose of study drug.
6. Subject must have adequate bone marrow function at Screening as follows:
a.Absolute Neutrophil Count (ANC) = 1.0 x 109/L (neutropenia due to marrow
infiltration may be supported by growth factors);
• b. Platelets = 75,000/mm3 (or = 50,000/mm3 for patients with bone marrow involvement
of lymphoma) within 7 days
7. Subject must have adequate coagulation, renal, and hepatic function, per laboratory
reference range at Screening as follows:
1. aPTT and PT not to exceed 1.5 × the upper limit of normal (ULN); Serum creatinine
not to exceed 2 x ULN, and a calculated creatinine clearance of at least 50
mL/min using the Cockcroft-Gault equation or a 24-hour urine collection;
2. AST or ALT = 3.0 × the upper normal limit (ULN) of institution's normal range;
Bilirubin = 1.5 × ULN. Subjects with documented Gilbert's Syndrome may have a
bilirubin > 1.5 × ULN.
8. Written informed consent form according to GCP and national regulations.
Exclusion Criteria:
1. Subject has known central nervous system involvement by MCL.
2. Prior malignancy other than MCL within the past 3 years, except for curatively treated
basal or squamous cell skin cancer, superficial bladder cancer, carcinoma in situ of
the cervix or breast, or localized Gleason score 6 prostate cancer.
3. Receiving any treatment with a moderate CYP3A4 inhibitor or strong CYP3A4 inhibitor or
inducer within 2 weeks (or 5 half-lives, whichever is longer) before the first dose of
study drug or requiring long-term use of strong CYP3A4 inhibitors or inducers.
4. Prior ASCT within the last 3 months; or prior autologous chimeric antigen receptor-T
cell therapy within the last 3 months; or prior allogeneic stem cell transplant within
the last 6 months or currently has an active graft-vs-host disease requiring the use
of immunosuppressants.
5. Major surgery within 4 weeks of screening.
6. Clinically significant cardiovascular disease including the following:
1. Myocardial infarction within 6 months before screening
2. Unstable angina within 3 months before screening
3. New York Heart Association class III or IV congestive heart failure
4. History of clinically significant arrhythmias (eg, sustained ventricular
tachycardia, ventricular fibrillation)
5. QT interval corrected based on Fridericia's formula (QTcF) > 480 msec.
6. History of Mobitz II second-degree or third-degree heart block without a
permanent pacemaker in place
7. Uncontrolled hypertension as indicated by a minimum of 2 consecutive blood
pressure measurements showing systolic blood pressure > 170 mmHg and diastolic
blood pressure > 105 mmHg at screening.
7. Prior exposure to a BCL2 inhibitor (e.g., venetoclax/ABT-199).
8. Prior exposure to a BTK inhibitor (e.g., ibrutinib, zanubrutinib).
9. History of hypersensitivity to excipient(s) of the sonrotoclax tablet.
10. Patients with unresolved hepatitis B or C infection or known HIV-positive infection:
1. Presence of hepatitis B surface antigen (HBsAg) or hepatitis B core antibody
(HBcAb). Patients with presence of HBcAb, but absence of HBsAg, are eligible if
hepatitis B virus (HBV) DNA is undetectable (< 20 IU/mL), and if they are willing
to undergo monitoring for HBV reactivation.
2. Presence of hepatitis C virus (HCV) antibody. Patients with presence of HCV
antibody are eligible if HCV RNA is undetectable (< 15 IU/mL), and if they are
willing to undergo monitoring for HCV reactivation.
11. Unable to swallow capsules or disease significantly affecting gastrointestinal
function such as malabsorption syndrome, resection of the stomach or small bowel,
bariatric surgery procedures, symptomatic inflammatory bowel disease, or partial or
complete bowel obstruction.
12. Pregnant or lactating women.
13. History of stroke or intracranial hemorrhage within 6 months before the first dose of
study drug.
14. Underlying medical conditions that, in the investigator's opinion, will render the
administration of study drug hazardous or obscure the interpretation of safety or
efficacy results.
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