| Eligibility |
Inclusion Criteria:
- Must have a confirmed diagnosis of chronic lymphocytic leukemia or small lymphocytic
lymphoma as per 2018 IWCLL criteria with evidence of persistent disease, defined as
measurable adenopathy or splenomegaly, circulating disease, or marrow disease
- On ibrutinib or acalabrutinib which was instituted due to patient previously meeting
2018 IWCLL criteria for treatment, started at least 6 months prior to study entry for
any patient who have received at least one prior line of therapy prior to ibrutinib or
acalabrutinib. Reduced dose of ibrutinib or acalabrutinib is allowed as long as the
dose has been stable for at least 4 weeks and all toxicities are = grade 1
- Must have achieved either SD, PR or PR-L on ibrutinib or acalabrutinib by 2018 IWCLL
criteria
- ECOG performance status < 2
- Patients must meet the following hematologic criteria at screening, unless they have
significant bone marrow involvement of CLL confirmed on biopsy:
- Absolute neutrophil count =500 cells/mm3 (0.5 x 109/L). Growth factor is allowed
in order to achieve this
- Platelet count =50,000 cells/mm3 independent of transfusion within 7 days of
screening
- Adequate hepatic function defined as: Serum aspartate transaminase (AST) and alanine
transaminase (ALT) = 3.0 x upper limit of normal (ULN), bilirubin =2.0 x ULN (unless
bilirubin rise is due to Gilbert's syndrome or of non-hepatic origin including
hemolysis)
- Adequate renal function defined by serum creatinine =1.5 x ULN or creatinine clearance
(by Cockroft-Gauldt = 50 ml/min
- Women of child-bearing potential and men must agree to use adequate contraception
(hormonal or barrier method of birth control; abstinence) prior to study entry and for
the duration of study participation
- Ability to understand and the willingness to sign a written informed consent document
Exclusion Criteria:
- Patients receiving cancer therapy (i.e., chemotherapy, radiation therapy,
immunotherapy, biologic therapy, hormonal therapy, surgery and/or tumor embolization)
other than ibrutinib or acalabrutinib within 2 weeks of Cycle 1/Day 1 with the
following exceptions:
- Limited palliative radiation is allowed if completed > 1 weeks of C1D1
- Hormonal therapy given in the adjuvant setting
- Corticosteroid therapy (prednisone or equivalent <15 mg daily) is allowed as
clinically warranted as long as the dose is stabilized at least for 7 days prior
to initial dosing.Topical or inhaled corticosteroids are permitted
- Within six months of allogeneic hematologic stem cell transplant at the time of
starting study treatment or active graft vs. host disease requiring systemic treatment
or prophylaxis within 6 weeks of starting study treatment
- Prior treatment with copanlisib
- Patients in CR on ibrutinib or acalabrutinib
- History of other malignancies, except:
- Malignancy treated with curative intent and with no known active disease present
for =2 years before the first dose of study drug and felt to be at low risk for
recurrence by treating physician
- Adequately treated non-melanoma skin cancer or lentigo maligna without evidence
of disease
- Adequately treated carcinoma in situ without evidence of disease.
- Low-risk prostate cancer on active surveillance
- Vaccinated with live, attenuated vaccines <4 weeks before first dose of study drug
- Active autoimmune disease requiring systemic treatment
- Recent infection requiring intravenous antibiotics that was completed =7 days before
the first dose of study drug, or any uncontrolled active systemic infection
- Known bleeding disorders (eg, von Willebrand's disease) or hemophilia
- History of stroke or intracranial hemorrhage within 6 months prior to enrollment
- Human immunodeficiency virus (HIV) or active hepatitis C virus (HCV) or hepatitis B
virus (HBV) infection
- CMV PCR positive at baseline
- Major surgery within 4 weeks of first dose of study drug
- History of or concurrent condition of interstitial lung disease of any severity and/or
severely impaired lung function (as judged by the investigator)
- Concurrent diagnosis of pheochromocytoma
- Uncontrolled arterial hypertension despite optimal medical management
- Type 1 or type 2 diabetes mellitus with a HgbA1c > 8.5%
- Any life-threatening illness, medical condition, or organ system dysfunction that, in
the investigator's opinion, could compromise the subject's safety
- Currently active, clinically significant cardiovascular disease, such as uncontrolled
arrhythmia or Class 3 or 4 congestive heart failure as defined by the New York Heart
Association Functional Classification; or a history of myocardial infarction, unstable
angina, or acute coronary syndrome within 6 months prior to randomization
- Unable to swallow capsules or malabsorption syndrome, disease significantly affecting
gastrointestinal function, or resection of the stomach or small bowel, symptomatic
inflammatory bowel disease or ulcerative colitis, or partial or complete bowel
obstruction
- Lactating or pregnant
- Patients with known CNS involvement
- Concurrent administration of medications or foods that are strong inhibitors or
inducers of CYP3A
- Known hypersensitivity to copanlisib, ibrutinib, or acalabrutinib
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