Copanlisib + Venetoclax for Lymphoma

Recruiting at 2 trial locations

Overseen By Jennifer Crombie, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Dana-Farber Cancer Institute

Must not be taking: CYP3A inhibitors, Herbal medications

Disqualifiers: Autoimmune disease, HIV, Hepatitis, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 1

48 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial does not specify if you must stop taking your current medications, but it does exclude certain medications. You cannot take strong inhibitors or inducers of CYP3A, certain anticoagulants like warfarin, or herbal medications within 7 days of starting the study treatment. It's best to discuss your current medications with the study team.

Is the combination of Copanlisib and Venetoclax safe for treating lymphoma?

Venetoclax, also known as Venclexta or Venclyxto, has been shown to have an acceptable safety profile in patients with chronic lymphocytic leukemia (CLL), with manageable side effects like neutropenia (low white blood cell count) and infections. While specific safety data for the combination of Copanlisib and Venetoclax in lymphoma is not provided, Venetoclax alone has been generally safe in human studies for similar conditions. ^{1 2 3 4 5}

How is the drug combination of Copanlisib and Venetoclax unique for treating lymphoma?

The combination of Copanlisib and Venetoclax is unique because Venetoclax is a first-in-class oral drug that specifically targets and inhibits the BCL-2 protein, which helps cancer cells survive. This combination may offer a novel approach for treating lymphoma by potentially enhancing the effectiveness of treatment through different mechanisms of action. ^{1 2 4 5 6}

What is the purpose of this trial?

This research study is evaluating the combination of two drugs, copanlisib and venetoclax, as a possible treatment for trelapsed/refractory diffuse large B-cell lymphoma (DLBCL) The names of the study drugs involved in this study are: * Copanlisib * Venetoclax

Research Team

Jennifer Crombie, MD

Principal Investigator

Dana-Farber Cancer Institute

Eligibility Criteria

Adults (≥18 years) with relapsed/refractory diffuse large B-cell lymphoma who have failed or are ineligible for stem cell transplant or CAR T-cell therapy. Participants must have adequate organ function, no severe autoimmune diseases, no recent major surgeries, and not be pregnant. They should agree to use effective contraception.

Inclusion Criteria

My condition worsened after stem cell transplant or CAR T-cell therapy, or I can't have these treatments.

Total bilirubin ≤ 1.5 x ULN (< 3 x ULN for patients with Gilbert's syndrome, patients with cholestasis due to compressive adenopathies of the hepatic hilum or documented liver involvement or with biliary obstruction due to lymphoma)

My platelet count is above 75,000 or above 50,000 if cancer has spread to my bone marrow.

Exclusion Criteria

I take medication for seizures.

I finished IV antibiotics for an infection less than a week ago or have an ongoing infection.

I am on preventive antibiotics with no active infection and my medication is not prohibited.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase I Treatment

Dose escalation of copanlisib and venetoclax to determine the maximum tolerated dose

28 days up to 1 year

Copanlisib IV on days 1, 8, and 15; Venetoclax orally daily

Phase II Treatment

Treatment with copanlisib and venetoclax at the recommended phase II dose

28 days

Follow-up

Participants are monitored for safety and effectiveness after treatment

Every 3 months up to 1 year

Long-term Follow-up

Monitoring overall survival and progression-free survival

Up to 5 years

Treatment Details

Interventions

• Copanlisib
• Venetoclax

Trial Overview The trial is testing a combination of two drugs, copanlisib and venetoclax, as potential treatments for those with difficult-to-treat B-cell lymphoma that has returned after treatment or hasn't responded to previous therapies.

Participant Groups

Group I: Recommended phase II dose (RP2D) Copanlisib + Venetoclax Experimental Treatment 2 Interventions

Patients will be treated with copanlisib in combination with venetoclax, administered at the Recommended phase II dose (RP2D).

Group II: Dose Escalation Copanlisib + Venetoclax Experimental Treatment 2 Interventions

Phase 1 * Dose escalation will occur using a 3+3 design * Copanlisib will be administered IV on days 1, 8 and 15 in 28 day cycle * Venetoclax will be administered orally daily for each 28-day cycle. During cycle 1, a venetoclax dose ramp-up is performed in the outpatient setting

Who Is Running the Clinical Trial?

Dana-Farber Cancer Institute

Lead Sponsor

Trials

1,128

Recruited

382,000+

AbbVie

Industry Sponsor

Trials

1,079

Recruited

535,000+

Founded

2013

Headquarters

North Chicago, USA

Known For

Immunology treatments

Top Products

Humira (adalimumab), Skyrizi (risankizumab), Rinvoq (upadacitinib)

Dr. Roopal Thakkar

AbbVie

Chief Medical Officer since 2023

MD from Wayne State University School of Medicine

Robert A. Michael

AbbVie

Chief Executive Officer

Bachelor's degree in Finance from the University of Illinois

Bayer

Industry Sponsor

Trials

2,291

Recruited

25,560,000+

Founded

1863

Headquarters

Leverkusen, Germany

Known For

Pharmaceutical Innovations

Top Products

Aspirin, Aleve, Yaz, Nexavar

Bill Anderson

Bayer

Chief Executive Officer since 2023

BSc in Chemical Engineering from the University of Texas, MSc in Chemical Engineering and Management from MIT

Michael Devoy

Bayer

Chief Medical Officer since 2014

MD, PhD

Findings from Research

Venetoclax is a highly effective treatment for relapsed or refractory chronic lymphocytic leukemia (CLL), achieving response rates of about 80% in clinical trials involving 240 patients from 2011 to 2016.

While venetoclax has an acceptable safety profile, common side effects include neutropenia and diarrhea, and there is a risk of tumor lysis syndrome (TLS), which can be managed through careful dose ramp-up and patient education, leading to no reported TLS events in ongoing trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Venetoclax: Management and Care for Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia . Brumbaugh Paradis, H., Alter, D., Llerandi, D.[2018]

Venetoclax is an effective oral treatment for relapsed or refractory chronic lymphocytic leukemia (CLL), showing durable responses and a manageable safety profile in clinical trials, including patients with poor prognostic factors.

In combination with rituximab, venetoclax significantly improved progression-free survival and achieved undetectable minimal residual disease compared to bendamustine plus rituximab, with benefits lasting for at least 36 months.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Venetoclax: A Review in Relapsed/Refractory Chronic Lymphocytic Leukemia. Scott, LJ.[2020]

The combination of venetoclax and obinutuzumab was found to be safe and well-tolerated in patients with relapsed/refractory or previously untreated chronic lymphocytic leukemia, with no dose-limiting toxicities observed during the study.

The treatment resulted in a high overall response rate of 95% in relapsed/refractory patients and 100% in previously untreated patients, with significant rates of undetectable minimal residual disease, indicating effective disease control.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 1b study of venetoclax-obinutuzumab in previously untreated and relapsed/refractory chronic lymphocytic leukemia. Flinn, IW., Gribben, JG., Dyer, MJS., et al.[2021]

In the phase III CLL14 trial, a 12-month treatment with venetoclax combined with obinutuzumab significantly improved progression-free survival and rates of undetectable minimal residual disease compared to traditional chemoimmunotherapy with chlorambucil and obinutuzumab in patients with untreated chronic lymphocytic leukaemia.

Venetoclax + obinutuzumab is a well-tolerated, chemotherapy-free treatment option for CLL, with manageable side effects like neutropenia, making it suitable for patients who cannot undergo intensive chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Venetoclax: A Review in Previously Untreated Chronic Lymphocytic Leukaemia. Blair, HA.[2021]

Venetoclax is an oral medication that selectively inhibits the BCL-2 protein, which helps cancer cells survive, thereby restoring the ability of these malignant cells to undergo programmed cell death (apoptosis).

It has been approved in the USA for treating chronic lymphocytic leukaemia (CLL) in patients with a specific genetic marker (17p deletion) who have already undergone at least one prior therapy, and it is being studied for various other blood cancers and conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Venetoclax: First Global Approval. Deeks, ED.[2018]

In a study involving 272 patients with relapsed or refractory chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL), higher concentrations of venetoclax led to a quicker reduction in lymphocyte counts and tumor size, resulting in a high objective response rate (ORR) of 84.8% at a daily dose of 400 mg.

Importantly, increasing the dose of venetoclax did not correlate with a higher risk of serious adverse events like neutropenia or infections, suggesting that the 400 mg daily regimen is both effective and safe for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of Venetoclax Exposure on Clinical Efficacy and Safety in Patients with Relapsed or Refractory Chronic Lymphocytic Leukemia. Freise, KJ., Jones, AK., Eckert, D., et al.[2018]

References

1. United States pubmed.ncbi.nlm.nih.gov

Venetoclax: Management and Care for Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia . [2018]

2. France pubmed.ncbi.nlm.nih.gov

Venetoclax: A Review in Relapsed/Refractory Chronic Lymphocytic Leukemia. [2020]

3. United States pubmed.ncbi.nlm.nih.gov

Phase 1b study of venetoclax-obinutuzumab in previously untreated and relapsed/refractory chronic lymphocytic leukemia. [2021]

4. New Zealand pubmed.ncbi.nlm.nih.gov

Venetoclax: A Review in Previously Untreated Chronic Lymphocytic Leukaemia. [2021]

5. New Zealand pubmed.ncbi.nlm.nih.gov

Venetoclax: First Global Approval. [2018]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Impact of Venetoclax Exposure on Clinical Efficacy and Safety in Patients with Relapsed or Refractory Chronic Lymphocytic Leukemia. [2018]