| Eligibility |
Inclusion Criteria:
1. Men and women = 18 years of age deemed eligible for treatment with full-dose R-CHOP
and ASCT by the qualified investigator.
2. Histologic diagnosis of MCL according to the World Health Organization classification
3. Previously untreated MCL with the following exceptions: (a) prior radiotherapy for
localized disease, (b) up to 7 days of corticosteroids (prednisone 100mg/day
equivalent), (c) up to one dose of single-agent chemotherapy (for example,
cyclophosphamide), (d) up to one cycle of R-CHOP or bendamustine-rituximab (BR).
Patients with exceptions (c) and (d) are eligible as long as all other eligibility
criteria are met AND at least a CT scan and bone marrow biopsy were performed prior to
chemotherapy.
4. Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2.
5. Presence of at least one radiologically measurable nodal or extranodal mass. A
measurable nodal mass must have a longest diameter =1.5 cm. A measurable extranodal
mass should have a longest diameter =1.0 cm.
6. Women of childbearing potential (WOCBP) who are sexually active must use highly
effective methods of contraception during treatment and up to 12 months after the last
dose of rituximab or R-CHOP, or 2 days after the last dose of acalabrutinib, whichever
is last administered. Examples of highly effective contraceptive methods include an
agreement to remain abstinent (ie, refrain from heterosexual intercourse), bilateral
tubal ligation, male sterilization, established proper use of hormonal contraceptives
that inhibit ovulation, hormone-releasing intrauterine devices, and copper
intrauterine devices. Men who are sexually active must use highly effective methods of
contraception during treatment and up to 6 months after the last dose of rituximab or
R-CHOP, or 2 days after the last dose of acalabrutinib, whichever is last
administered. Men require an agreement to remain abstinent (ie, refrain from
heterosexual intercourse) or use a condom, and an agreement to refrain from donating
sperm. Periodic abstinence and withdrawal are not acceptable methods of contraception.
Fertility preservation options should be discussed.
7. Willing and able to participate in all required evaluations and procedures in this
study protocol including swallowing capsules without difficulty.
8. Ability to understand the purpose and risks of the study and provide signed and dated
informed consent and authorization to use protected health information
Exclusion Criteria:
1. Secondary central nervous system involvement.
2. Prior exposure to a BCR inhibitor (eg, BTK inhibitors, phosphoinositide-3 kinase
(PI3K), or Syk inhibitors) or BCL-2 inhibitor.
3. Prior malignancy (or any other malignancy requiring active treatment), except for
adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer,
or other cancer from which the subject has been disease free for = 2 years or which
will not limit survival to < 5 years. Subjects receiving adjuvant hormonal therapy for
early breast or prostate cancer are eligible.
4. Clinically significant cardiovascular disease such as uncontrolled or symptomatic
arrhythmias, congestive heart failure, or myocardial infarction within 6 months of
screening, or any Class 3 or 4 cardiac disease as defined by the New York Heart
Association Functional Classification. Subjects with controlled, asymptomatic atrial
fibrillation during screening can enroll on study.
5. Difficulty with or unable to swallow oral medication, or conditions significantly
affecting gastrointestinal function that would limit absorption of oral medication.
6. Known history of infection with HIV or any significant active infection (eg,
bacterial, viral or fungal), including suspected or confirmed progressive multifocal
leukoencephalopathy.
7. Known history of drug-specific hypersensitivity or anaphylaxis to study drugs
(acalabrutinib and individual components of R-CHOP), including active product or
excipient components.
8. Active bleeding or history of bleeding diathesis (eg, hemophilia or von Willebrand
disease).
9. Uncontrolled AIHA (autoimmune hemolytic anemia) or ITP (idiopathic thrombocytopenic
purpura).
10. Requires treatment with a strong cytochrome P450 3A4 (CYP3A4) inhibitor/inducer.
11. Requires or receiving anticoagulation with warfarin or equivalent vitamin K
antagonists (eg, warfarin).
12. Requires treatment with proton pump inhibitors (eg, omeprazole, esomeprazole,
lansoprazole, dexlansoprazole, rabeprazole, or pantoprazole). Subjects receiving
proton pump inhibitors who switch to H2-receptor antagonists or antacids are eligible
for enrollment to this study.
13. History of significant cerebrovascular disease/event, including stroke or intracranial
hemorrhage, within 6 months before the first dose of study drug.
14. Major surgical procedure within 4 weeks of first dose of study drug. Note: If a
subject had major surgery, they must have recovered adequately from any toxicity
and/or complications from the intervention before the first dose of study drug.
15. Received a live virus vaccination within 28 days of first dose of R-CHOP +
acalabrutinib.
16. Hepatitis B or C serologic status: subjects who are hepatitis B core antibody
(anti-HBc) positive and who are surface antigen negative will need to have a negative
polymerase chain reaction (PCR). Those who are hepatitis B surface antigen (HbsAg)
positive or hepatitis B PCR positive will be excluded.
Subjects who are hepatitis C antibody positive will need to have a negative PCR
result. Those who are hepatitis C PCR positive will be excluded. Subjects with a
history of Hepatitis C who received antiviral treatment are eligible as long as PCR is
negative.
17. ANC <1.0 x109/L (subjects with bone marrow involvement by lymphoma are eligible
regardless of ANC)
18. Platelets <50 x109/L (subjects with bone marrow involvement by lymphoma are eligible
regardless of platelet count)
19. Total serum bilirubin >2 times the upper limit of normal (or <3 times for Gilbert's
disease or documented hepatic involvement by lymphoma), AST and ALT <3 times the upper
limit of normal (or <5 times for documented hepatic involvement by lymphoma)
20. Creatinine clearance <30 mL/min.
21. PT/INR >2 times the upper limit of normal in the absence of anticoagulants and/or PTT
>2 times the upper limit of normal in the absence of anticoagulants.
22. Breastfeeding or pregnant. WOCBP must have a serum pregnancy test done a maximum of 7
days prior to treatment initiation and a negative result must be documented prior to
recruitment.
23. Concurrent participation in another therapeutic clinical trial.
24. Evidence of disease (such as severe or uncontrolled systemic diseases, including
uncontrolled hypertension and renal transplant) that, in the investigator's opinion,
make it undesirable for the patient to participate in the study or that would
jeopardize compliance with the protocol.
25. Received any investigational drug within 30 days or 5 half-lives (whichever is
shorter) before first dose of study drug.
26. Current life-threatening illness, medical condition, or organ system dysfunction
which, in the Investigator's opinion, could compromise the subject's safety or put the
study at risk.
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