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Chronic Lymphocytic Leukemia (CLL)Phase 2NCT04685915

Copanlisib Plus Ibrutinib or Acalabrutinib in R/R CLL

A Phase 2 study testing Ibrutinib, Copanlisib and Acalabrutinib in people with Chronic Lymphocytic Leukemia (CLL), run by Inhye Ahn.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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Trial summary

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

Who is it for?
Ages 18 years and older
Conditions the study is for
Chronic Lymphocytic Leukemia (CLL)
What is being tested?
Ibrutinib, Copanlisib and Acalabrutinib
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
No sites listed yet
Study dates
18 Feb 2021to 1 Mar 2028
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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

Who cannot join

  • 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
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  • 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

About this study

Official title: A Phase II Study of Copanlisib to Deepen Response in CLL Patients on Ibrutinib or Acalabrutinib in the Relapsed/Refractory Setting

This research study is examining the effect of adding a fixed duration of copanlisib to ibrutinib or acalabrutinib in select participants who have been on ibrutinib or acalabrutinib 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
  • Acalabrutinib
Read the detailed description

This is an open-label, phase II study, adding copanlisib to ibrutinib or acalabrutinib 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 and acalabrutinib are 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 or acalabrutinib 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 and acalabrutinib will be obtained from commercial supply.

Being tested
Ibrutinib, Copanlisib, Acalabrutinib
Keywords
Chronic Lymphocytic Leukemia (CLL), Ibrutinib, Acalabrutinib, Copanlisib
Medical subject headings
Leukemia, Lymphocytic, Chronic, B-Cell

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • IbrutinibDrug

    Also called Imbruvica

    Capsule, taken by mouth once daily

  • CopanlisibDrug

    Also called Aliqopa

    Intravenous Infusion

  • AcalabrutinibDrug

    Also called Calquence

    Capsule, taken by mouth twice daily

Study groups in NCT04685915
Study groupRoleWhat they receive
Addition of copanlisib to either ibrutinib or acalabrutinibExperimentalDuring the 28-day study treatment cycles, participants will: * Continue to take ibrutinib (daily) or acalabrutinib (twice a day) at a 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.
Receives: Drug: Ibrutinib; Drug: Copanlisib; Drug: Acalabrutinib

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Complete response (CR) Rate

    Rate of complete response (CR) by 2018 IWCLL criteria following the addition of six months of copanlisib to the therapy of patients with SD or PR or PR-L on ibrutinib or acalabrutinib in the relapsed/refractory setting.

    Measured: 6 months

Secondary outcomes (4)

  1. Number of Participants with Treatment Related Adverse Events as Assessed by CTCAE ver. 5.0.

    Adverse events will be collected and reported as percentages

    Measured: 6 months

  2. Duration of Response (DOR)

    Legnth of time the patients respond to therapy

    Measured: 3 years

  3. Progression-free Survival (PFS)

    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.

    Measured: 3 years

  4. Overall Survival (OS)

    The time from registration to death due to any cause or censored at date last known alive.

    Measured: 3 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted28 Dec 2020
  2. Study start18 Feb 2021
  3. Primary completion1 Mar 2023 (estimated)
  4. Study completion1 Mar 2028 (estimated)

Why it stopped: Bayer is no longer funding due to lack of accrual

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04685915
Sponsor's protocol ID
20-281
Status last verified
Jan 2023
First submitted
22 Dec 2020
Last updated
22 May 2025
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: The Dana-Farber / Harvard Cancer Center encourages and supports the responsible and ethical sharing of data from clinical trials. De-identified participant data from the final research dataset used in the published manuscript may only be shared under the terms of a Data Use Agreement. Requests may be directed to: \[contact information for Sponsor Investigator or designee\]. The protocol and statistical analysis plan will be made available on Clinicaltrials.gov only as required by federal regulation or as a condition of awards and agreements supporting the research.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Ibrutinib, Copanlisib and Acalabrutinib in people with Chronic Lymphocytic Leukemia (CLL), run by Inhye Ahn.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 11 inclusion and 31 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: withdrawn, as of the sponsor's last update on 22 May 2025. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was withdrawn before enrolling participants, so there are no results.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Complete response (CR) Rate (time frame: 6 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04685915.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 May 2025.

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