Gender
All
Age Group
18 Years to 70 Years
Accepting Healthy Volunteers
No
Inclusion Criteria:
- Baseline measurements and evaluations must be obtained within 6 weeks of
randomization to the study. Abnormal PET or CT scans may constitute evaluable
disease. Patient must have at least one objective measurable disease parameter.
Measurable disease in the liver is required if the liver is the only site of
lymphoma.
- MIPI score must be calculated and entered in Oncology Patient Enrollment Network
(OPEN).
- Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status
score of 0-2.
- Patients must have untreated histologically confirmed mantle cell lymphoma, with
cyclin D1 (BCL1) expression by immunohistochemical stains and/or t(11;14) by
cytogenetics or fluorescent in situ hybridization (FISH). The diagnosis must be
confirmed by formal hematopathology review at the enrolling center.
- Patients being treated with gastric reducing agents proton pump inhibitors must be
switched to an alternative drug before starting acalabrutinib.
- Absolute neutrophil count (ANC) >= 1,000/mcL (obtained with 14 days of
randomization). If disease includes marrow involvement or hypersplenism, please
reference the below revised ANC requirement:
- ANC >= 500/mcL
- Platelets >= 75,000 mcL (obtained with 14 days of randomization). If disease
includes involvement or hypersplenism, please reference the below revised platelet
requirement:
- Platelets >= 25,000/mcL
- Total bilirubin =< 2 x institutional upper limit of normal (ULN) (obtained with 14
days of randomization). If disease includes hepatic infiltration or is causing
biliary obstruction, or if elevated bilirubin is due to Gilbert's disease, please
reference the below revised bilirubin requirements:
- Bilirubin =< 3 x institutional ULN
- Aspartate aminotransferase (AST) and alanine transaminase (ALT) =< 2.5 x
institutional ULN (obtained with 14 days of randomization). If disease includes
hepatic infiltration or is causing biliary obstruction, or if elevated bilirubin is
due to Gilbert's disease, please reference the below revised AST/ALT requirements:
- AST/ALT =< 5 x institutional ULN
- Prothrombin time (PT)/international normalized ratio (INR) or partial thromboplastin
time (aPTT) in the absence of lupus anticoagulant) < 2 x institutional ULN (obtained
with 14 days of randomization). Patients receiving anticoagulant therapy (other than
warfarin or equivalent vitamin K antagonists which are excluded), higher INR/aPTT
may be permitted to enroll to this study after discussion with the primary
investigator (PI).
- Creatinine =< institutional ULN, OR glomerular filtration rate (GFR) >= 40
mL/min/1.73 m^2 (obtained with 14 days of randomization).
- Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral
therapy with undetectable viral load within 6 months are eligible for this trial.
- For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV
viral load must be undetectable on suppressive therapy, if indicated.
- Patients with a history of hepatitis C virus (HCV) infection must have been treated
and cured. For patients with HCV infection who are currently on treatment, they are
eligible if they have an undetectable HCV viral load.
- Patients with a prior or concurrent malignancy whose natural history or treatment
does not have the potential to interfere with the safety or efficacy assessment of
the investigational regimen are eligible for this trial.
- Patients with known history or current symptoms of cardiac disease, or history of
treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac
function using the New York Heart Association Functional classification. To be
eligible for this trial, patients should be class 2B or better.
- Patients must have a QT interval (QTc) =< 480 msec obtained within 14 days of
randomization.
- Women must not be pregnant or breast-feeding due to the potential harm to an unborn
fetus and possible risk for adverse events in nursing infants with the treatment
regimens being used. Patients must also not expect to conceive or father children
from the time of registration, while on study treatment, and until 12 months after
the last dose of study treatment. All females of childbearing potential must have a
blood test or urine study within 2 weeks prior to randomization to rule out
pregnancy. A female of childbearing potential is any woman, regardless of sexual
orientation or whether they have undergone tubal ligation, who meets the following
criteria: has achieved menarche at some point, has not undergone a hysterectomy or
bilateral oophorectomy; or has not been naturally postmenopausal (amenorrhea
following cancer therapy does not rule out childbearing potential) for at least 24
consecutive months (i.e., has had menses at any time in the preceding 24 consecutive
months).
- Women of childbearing potential and sexually active males must agree to use accepted
and effective method(s) of contraception or to abstain from sexual intercourse for
the duration of their participation in the study and for 12 months after treatment
ends.
- Patients are not eligible if they require treatment with a strong cytochrome P450
(CYP) 3A inhibitor.
- Patients may not have received the following within 7 days prior to the first dose
of study drug:
- Strong and moderate CYP3A inhibitors
- Strong and moderate CYP3A inducers
- Patients are ineligible if they have any of the following:
- Malabsorption syndrome or disease significantly affecting gastrointestinal
function.
- Active bleeding or history of bleeding diathesis (e.g. hemophilia or von
Willebrand disease).
- Uncontrolled AIHA (autoimmune hemolytic anemia) or ITP (idiopathic
thrombocytopenia purpura).
- Requires or receiving anticoagulation with warfarin or equivalent vitamin K
antagonists (e.g. phenprocoumon) within 7 days of first dose of study drug.
- History of significant cerebrovascular disease/event, including stroke or
intracranial hemorrhage, within 6 months before the first dose of study drug.
- Known active bacterial, viral, fungal, mycobacterial, parasitic, or other
infections at study enrollment (defined as exhibiting ongoing signs/symptoms
related to the infection and without improvement, despite appropriate
antibiotics or other treatment).
- History of severe allergic reaction attributed to compounds of similar chemical
or biologic composition to rituximab, bendamustine, cytarabine, or
acalabrutinib.
- Patients must be able to fulfill one of the following eligibility requirements
pertaining to biospecimen availability for submission following randomization:
- Archived formalin-fixed paraffin-embedded (FFPE) tumor tissue specimen from the
original diagnostic biopsy is available for submission OR,
- If tumor tissue is not available, peripheral blood collected prior to
initiation of protocol therapy will be submitted
- NOTE: Biospecimens must be submitted within 60 days following
randomization to Adaptive Biotechnologies for ClonoSEQ ID molecular marker
identification of unique clonal immunoglobulin deoxyribonucleic acid (DNA)
sequence. If peripheral blood will be submitted, Adaptive Biotechnologies
should be contacted prior to patient randomization for guidance pertaining
to collection and submission requirements.