| Eligibility |
Inclusion Criteria:
1. Men and women = 18 years of age.
2. Diagnosed with aggressive B cell non-Hodgkin lymphoma
- Diffuse large B cell lymphoma (Both GCB and non-GCB)
: GCB type should not be more than 40% (N=26) of whole study population (Would
limit number of GCB patients by maximum of 26)
- Primary mediastinal B cell lymphoma
- Transformed follicular lymphoma
- Small lymphocytic lymphoma with Richter transformation
3. Failed previous treatments and last dose administered must be more than 2-week ahead
from enrollment
- Should have received anti-CD20 based chemotherapy previously
- Failed at least two lines of therapy if patient is candidate for autologous stem
cell transplantation
- Failed frontline therapy if patient is ineligible for autologous stem cell
transplantation
4. Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2
5. Woman of childbearing potential (WOCBP) who are sexually active must have 2 negative
urine hCG test prior to first dose, then every week for the first month of study
period, then every 4 weeks afterwards during treatment period if menses are regular or
every 2 weeks if menses are irregular. Urine hCG test must be done 4 weeks after the
last dose of acalabrutinib, lenalidomide and rituximab. WOCBP must use 2 methods
including at least 1 highly effective method of contraception for 4 weeks prior to
first dose, during treatment period and for 4 weeks after the last dose of
acalabrutinib, lenalidomide and for 12 months after the last dose of rituximab. Men
who are sexually active must use condoms during treatment period and 4 weeks after the
last dose of any study drug.
6. Willing and able to participate in all required evaluations and procedures in this
study protocol including swallowing capsules without difficulty.
7. 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. Diagnosed with mantle cell lymphoma
2. Previously treated with more than four lines of chemotherapy (Consolidative autologous
stem cell transplantation is deemed as the same line therapy)
3. Previously treated with allogeneic hematopoietic stem cell transplantation within 6
months
4. GVHD requiring treatment
5. Patient who cannot take drug per oral
6. Known resistance to both BTK inhibitor and lenalidomide (Progression free survival to
both BTK inhibitor and lenalidomide < 6 months)
7. Known resistant mutation to BTK inhibitor (BTKC481S and PLGCR665W)
8. Prior malignancy (or any other malignancy that requires 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 = 5 years or which
will not limit survival to < 5 years.
9. 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.
10. Malabsorption syndrome, disease significantly affecting gastrointestinal function, or
resection of the stomach or small bowel that is likely to affect absorption,
symptomatic inflammatory bowel disease, partial or complete bowel obstruction, or
gastric restrictions and bariatric surgery, such as gastric bypass.
11. Known history of infection with HIV or any uncontrolled active systemic infection (eg,
bacterial, viral or fungal).
12. Known history of drug-specific hypersensitivity or anaphylaxis to study drug
(including active product or excipient components).
13. Active bleeding, history of bleeding diathesis (eg, hemophilia or von Willebrand
disease).
14. Uncontrolled AIHA (autoimmune hemolytic anemia) or ITP (idiopathic thrombocytopenic
purpura).
15. Requires treatment with a strong cytochrome P450 3A4 (CYP3A4) inhibitor/inducer.
16. Requires or receiving anticoagulation with warfarin or equivalent vitamin K
antagonists (eg, phenprocoumon) within 7 days of first dose of study drug.
17. Prothrombin time/INR or aPTT (in the absence of Lupus anticoagulant) > 2x ULN.
18. 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.
19. History of significant cerebrovascular disease or event, including stroke or
intracranial hemorrhage, within 6 months before the first dose of study drug.
20. Major surgical procedure within 28 days 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.
21. 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. Those who are positive only for
anti-HBc and negative for HbsAg and hepatitis B PCR need to receive adequate antiviral
prophylaxis for hepatitis B during the study period.
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.
22. Active tuberculosis (history of exposure or history of positive tuberculin test; plus
presence of clinical symptoms, physical or radiographic findings). Subjects with
latent tuberculosis infection who are deemed to require treatment by the investigator
are not eligible.
23. Uncontrolled active infection as determined by the investigator.
24. WBC < 3,000 /µL, ANC < 1,000 /µL, Platelets < 75,000 /µL, or Hemoglobin < 9.0 g/dL.
Correction with transfusion within 2 weeks is not allowed.
25. Total bilirubin > 2 x ULN, or AST, ALT > 3 x ULN
26. Cr > 1.5 x ULN or CLcr < 30 mL/min/1.73m2
27. Breastfeeding or pregnant.
28. Concurrent participation in another therapeutic clinical trial.
|
