8 Participants Needed

Copanlisib + Venetoclax for Mantle Cell Lymphoma

Recruiting at 1 trial location
Age: 18+
Sex: Any
Trial Phase: Phase 1 & 2
Sponsor: City of Hope Medical Center
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)

Trial Summary

What is the purpose of this trial?

This phase I/II trial studies the side effects, best dose, and effectiveness of copanlisib and venetoclax in treating patients with mantle cell lymphoma that has come back (relapsed) or does not respond to treatment (refractory). Copanlisib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Venetoclax may stop the growth of cancer cells by blocking Bcl-2, a protein needed for cancer cell survival. Giving copanlisib and venetoclax may help treat patients with mantle cell lymphoma.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you cannot take medications or foods that strongly affect CYP3A4 within 7 days of starting the study treatment, and you cannot be on high-dose corticosteroids.

What data supports the effectiveness of the drug combination Copanlisib and Venetoclax for treating Mantle Cell Lymphoma?

Venetoclax has shown effectiveness in treating Mantle Cell Lymphoma (MCL) when combined with other drugs, achieving high response rates and minimal residual disease clearance in patients. Additionally, Venetoclax has been effective in treating other types of blood cancers, such as chronic lymphocytic leukemia, with good response rates and safety profiles.12345

Is the combination of Copanlisib and Venetoclax safe for treating Mantle Cell Lymphoma?

Venetoclax has been generally well tolerated in patients with various types of non-Hodgkin lymphoma, including mantle cell lymphoma, with most side effects being mild to moderate. Common serious side effects include low blood cell counts, which can be managed with supportive care and dose adjustments.13467

What makes the drug combination of Copanlisib and Venetoclax unique for treating Mantle Cell Lymphoma?

The combination of Copanlisib and Venetoclax is unique because it targets specific proteins involved in cancer cell survival, potentially offering a new approach for treating Mantle Cell Lymphoma, a condition with limited standard treatment options. Venetoclax is known for its ability to inhibit BCL-2, a protein that helps cancer cells survive, while Copanlisib targets different pathways, which may enhance the overall effectiveness of the treatment.12468

Research Team

AD

Alexey Danilov

Principal Investigator

City of Hope Medical Cneter

Eligibility Criteria

This trial is for adults with mantle cell lymphoma that has returned or isn't responding to treatment. Participants must be able to take pills, have a life expectancy of at least 3 months, and proper organ function. They should not have HIV, hepatitis B or C, uncontrolled diseases like diabetes or heart conditions, and women must not be pregnant.

Inclusion Criteria

You are able to swallow pills or take medication by mouth.
Your doctor believes you will live for at least 3 more months.
Aspartate aminotransferase (AST) =< 2.5 x ULN (to be performed within 30 days prior to day 1 of protocol therapy unless otherwise stated)
See 30 more

Exclusion Criteria

You have already been treated with venetoclax or other experimental drugs that target BCL2, or with copanlisib.
- All other chemotherapy, radiation therapy within 30 days prior to initiation of therapy
- Targeted therapy within 6 half-lives
See 27 more

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive copanlisib intravenously on days 1, 8, and 15, and venetoclax orally daily on days 1-28. Treatment repeats every 28 days for up to 26 cycles.

Up to 2 years
3 visits per cycle (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment completion every 3 months for 2 years.

2 years
Every 3 months

Treatment Details

Interventions

  • Copanlisib Hydrochloride
  • Venetoclax
Trial Overview The trial is testing the combination of two drugs: Copanlisib Hydrochloride and Venetoclax. It aims to find the safest doses and see how effective they are against relapsed or refractory mantle cell lymphoma by blocking enzymes and proteins cancer cells need to grow.
Participant Groups
1Treatment groups
Experimental Treatment
Group I: Treatment (copanlisib hydrochloride, venetoclax)Experimental Treatment2 Interventions
Patients receive copanlisib hydrochloride IV over 1 hour on days 1, 8, and 15, and venetoclax PO QD on days 1-28. Treatment repeats every 28 days for up to 26 cycles in the absence of disease progression or unacceptable toxicity. Copanlisib will be given at 30mg, 45mg, or 60 mg depending on the assigned dose level. Venetoclax will have a weekly dose ramp up from 20mg, 50mg, 100mg, 200mg, and then 400mg thereafter.

Find a Clinic Near You

Who Is Running the Clinical Trial?

City of Hope Medical Center

Lead Sponsor

Trials
614
Recruited
1,924,000+

National Cancer Institute (NCI)

Collaborator

Trials
14,080
Recruited
41,180,000+

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.
Venetoclax: Management and Care for Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia .Brumbaugh Paradis, H., Alter, D., Llerandi, D.[2018]
In a multicenter study of 28 patients with untreated mantle cell lymphoma (MCL), the combination of lenalidomide, rituximab, and venetoclax demonstrated a high overall response rate of 96% and a complete response rate of 86%, indicating strong efficacy for this treatment regimen.
The treatment was found to be safe, with no dose-limiting toxicities reported, although common side effects included neutropenia and thrombocytopenia, suggesting that this combination could be a promising option for patients who are ineligible for transplantation.
Adding venetoclax to lenalidomide and rituximab is safe and effective in patients with untreated mantle cell lymphoma.Phillips, TJ., Bond, D., Takiar, R., et al.[2023]
In a phase I trial involving 106 patients with various subtypes of non-Hodgkin lymphoma, venetoclax, a BCL-2 inhibitor, was found to be generally well tolerated, with a 44% overall response rate across different lymphoma types.
The study identified 1,200 mg as the recommended dose for future studies in follicular lymphoma and diffuse large B-cell lymphoma, while 800 mg was effective for mantle cell lymphoma, indicating varying efficacy based on lymphoma subtype.
Phase I First-in-Human Study of Venetoclax in Patients With Relapsed or Refractory Non-Hodgkin Lymphoma.Davids, MS., Roberts, AW., Seymour, JF., et al.[2018]

References

Venetoclax: Management and Care for Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia . [2018]
Adding venetoclax to lenalidomide and rituximab is safe and effective in patients with untreated mantle cell lymphoma. [2023]
Venetoclax for Patients With Chronic Lymphocytic Leukemia With 17p Deletion: Results From the Full Population of a Phase II Pivotal Trial. [2019]
Phase I First-in-Human Study of Venetoclax in Patients With Relapsed or Refractory Non-Hodgkin Lymphoma. [2018]
Ibrutinib, obinutuzumab, and venetoclax in relapsed and untreated patients with mantle cell lymphoma: a phase 1/2 trial. [2021]
Venetoclax: First Global Approval. [2018]
Venetoclax: A Review in Previously Untreated Chronic Lymphocytic Leukaemia. [2021]
The path to venetoclax resistance is paved with mutations, metabolism, and more. [2023]
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