Clinical Trials /

Copanlisib Plus Ibrutinib in R/R CLL

NCT04685915

Description:

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

Related Conditions:
  • Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Copanlisib Plus Ibrutinib in R/R CLL
  • Official Title: A Phase II Study of Copanlisib to Deepen Response in CLL Patients on Ibrutinib in the Relapsed/Refractory Setting

Clinical Trial IDs

  • ORG STUDY ID: 20-281
  • NCT ID: NCT04685915

Conditions

  • Chronic Lymphocytic Leukemia (CLL)
  • Relapsed Chronic Lymphocytic Leukemia
  • Refractory Chronic Lymphocytic Leukemia

Interventions

DrugSynonymsArms
IbrutinibImbruvicaIbrutinib + Copanlisib
CopanlisibAliqopaIbrutinib + Copanlisib

Purpose

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

Detailed Description

      This is an open-label, phase II study, adding copanlisib to ibrutinib in select participants
      who are receiving ibrutinib for relapsed/refractory CLL.

      Copanlisib has not been approved by the U.S. Food and Drug Administration (FDA) for CLL, but
      it has been approved for use in relapsed/refractory follicular lymphoma. Ibrutinib is
      approved by the FDA as a treatment option for CLL.

      This research study is:

        -  Trying to understand what effects, good or bad, treatment with copanlisib in combination
           with ibrutinib has in select participants who are receiving ibrutinib for
           relapsed/refractory CLL

        -  Determining if this approach is better or worse than the usual approach for this type of
           cancer

        -  Determining whether genomic changes in CLL cells and changes in immune response make
           treatment with the study drugs more or less effective

      The research study procedures include screening for eligibility and study treatment including
      evaluations and follow up visits.

      Participants will receive combination therapy for six months before resuming ibrutinib alone.
      They will continue therapy for as long as they do not have serious side effects and their
      disease does not get worse and will be followed for up to 5 years.

      It is expected that about 30 people will take part in this research study.

      Bayer HealthCare Pharmaceuticals is supporting this research study by providing the study
      drug, copanlisib. Ibrutinib will be obtained from commercial supply.
    

Trial Arms

NameTypeDescriptionInterventions
Ibrutinib + CopanlisibExperimentalDuring 28 day study treatment cycle, participants will: Take Ibrutinib daily at predetermined dose for as long as there are no serious side effects and disease progression Receive intravenous infusion of Copanlisib at a predetermined dose days 1, 8 and 15 for cycles 1-6.
  • Ibrutinib
  • Copanlisib

Eligibility 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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Complete response (CR) Rate
Time Frame:6 months
Safety Issue:
Description:Rate of complete response (CR) by 2018 IW-CLL criteria following the addition of six months of copanlisib to the therapy of patients with SD or PR or PR-L on ibrutinib in the relapsed/refractory setting.

Secondary Outcome Measures

Measure:Number of Participants with Treatment Related Adverse Events as Assessed by CTCAE ver. 5.0.
Time Frame:6 months
Safety Issue:
Description:Adverse events will be collected and reported as percentages
Measure:Duration of Response (DOR)
Time Frame:3 years
Safety Issue:
Description:Legnth of time the patients respond to therapy
Measure:Progression-free Survival PFS
Time Frame:3 years
Safety Issue:
Description:The time from registration to progression or death due to any cause. Participants alive without disease progression are censored at date of last disease evaluation.
Measure:Overall Survival
Time Frame:3 years
Safety Issue:
Description:The time from registration to death due to any cause or censored at date last known alive.
Measure:Genomic Mutation Rates
Time Frame:3 years
Safety Issue:
Description:RNA and DNA Sequencing will be performed and correlated with outcome

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Dana-Farber Cancer Institute

Trial Keywords

  • Chronic Lymphocytic Leukemia (CLL)
  • Frontline Chronic Lymphocytic Leukemia (CLL)
  • Relapsed Chronic Lymphocytic Leukemia
  • Refractory Chronic Lymphocytic Leukemia

Last Updated

December 28, 2020