Copanlisib Plus Ibrutinib or Acalabrutinib in R/R CLL

NCT04685915 | Withdrawn Phase 2 DMC FDA Drug

• 1 other identifier: 20-281
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief 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). The names of the study drugs involved in this study are:

• Copanlisib
• Ibrutinib
• Acalabrutinib

Conditions

Chronic Lymphocytic Leukemia (CLL)

Keywords

Chronic Lymphocytic Leukemia (CLL); Ibrutinib; Acalabrutinib; Copanlisib

Outcome Measures

Primary Outcomes (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.

  6 months

Secondary Outcomes (4)

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

  6 months

• Duration of Response (DOR)

  3 years

• Progression-free Survival (PFS)

  3 years

• Overall Survival (OS)

  3 years

Study Arms (1)

Addition of copanlisib to either ibrutinib or acalabrutinib

EXPERIMENTAL

During 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.

Drug: Ibrutinib; Drug: Copanlisib; Drug: Acalabrutinib

Interventions

Ibrutinib DRUG

Capsule, taken by mouth once daily

Also known as: Imbruvica

Addition of copanlisib to either ibrutinib or acalabrutinib

Copanlisib DRUG

Intravenous Infusion

Also known as: Aliqopa

Addition of copanlisib to either ibrutinib or acalabrutinib

Acalabrutinib DRUG

Capsule, taken by mouth twice daily

Also known as: Calquence

Addition of copanlisib to either ibrutinib or acalabrutinib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Inhye Ahn: lead
• Bayer: collaborator

MeSH Terms

Conditions

Leukemia, Lymphocytic, Chronic, B-Cell

Interventions

ibrutinib; copanlisib; acalabrutinib

Condition Hierarchy (Ancestors)

Leukemia, B-Cell; Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Inhye Ahn, MD

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Sponsor Investigator

Study Record Dates

• First Submitted: December 22, 2020
• First Posted: December 28, 2020
• Study Start: February 18, 2021
• Primary Completion: March 1, 2023
• Study Completion (Estimated): March 1, 2028
• Last Updated: May 22, 2025

Record last verified: 2023-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Data can be shared no earlier than 1 year following the date of publication
• Access Criteria: Contact the Belfer Office for Dana-Farber Innovations (BODFI) at innovation@dfci.harvard.edu