Copanlisib Plus Ibrutinib in R/R CLL

• Status: Recruiting
• Trial end date: 2028-03-01
• Target enrollment: 0
• Participant gender: All

Summary

This research study is examining the effect of adding a fixed duration of copanlisib to ibrutinib in select participants who have been on ibrutinib for at least six months for relapsed/refractory chronic lymphocytic leukemia (CLL).

The names of the study drugs involved in this study are:

• Copanlisib

• Ibrutinib

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Dana-Farber Cancer Institute
• Collaborator: Bayer

Criteria

Inclusion Criteria:

• Must have a confirmed diagnosis of chronic lymphocytic leukemia or small lymphocytic ymphoma as per IW-CLL 2018 criteria with evidence of persistent disease, defined as measurable adenopathy or splenomegaly, circulating disease, or marrow disease

• On ibrutinib which was instituted due to the patient previously meeting IWCLL 2018 criteria for treatment, started at least 6 months prior to study entry

• Must have received at least one prior line of therapy for CLL prior to ibrutinib

• Must have achieved either SD, PR or PR-L (with residual lymphadenopathy in addition to lymphocytosis) on ibrutinib by IW-CLL 2018 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

• Age greater than or equal to 18 years.

• 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 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, or in partial response with residual lymphocytosis (PR-L) as their only remaining evidence of disease on ibrutinib

• 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

• 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)

• 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 HbA1c > 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 or ibrutinib