18 Participants Needed

Copanlisib + Ibrutinib for Central Nervous System Lymphoma

Recruiting at 8 trial locations
CG
Ingo Mellinghoff, MD profile photo
Overseen ByIngo Mellinghoff, MD
Age: 18+
Sex: Any
Trial Phase: Phase 1 & 2
Sponsor: Memorial Sloan Kettering Cancer Center
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)

Trial Summary

Do I need to stop my current medications to join the trial?

Yes, you may need to stop certain medications before joining the trial. Specifically, you must stop using warfarin or other vitamin K antagonists 7 days before starting the trial drug, and strong CYP3A4/5 inhibitors and inducers 2 weeks prior. Additionally, enzyme-inducing antiepileptic drugs should be switched to non-inducing alternatives 2 weeks before starting the trial.

What data supports the effectiveness of the drugs Copanlisib and Ibrutinib for treating central nervous system lymphoma?

Research shows that Ibrutinib, a drug that can cross the blood-brain barrier, has been effective in treating central nervous system lymphomas, with studies reporting good response rates and improved survival compared to traditional chemotherapy. Additionally, Ibrutinib has shown promise in maintaining remission in patients with primary central nervous system lymphoma.12345

What safety data exists for Ibrutinib in treating central nervous system lymphoma?

Ibrutinib, used alone or with other treatments, has shown good tolerance in patients with central nervous system lymphoma, but there is a risk of increased aspergillosis (a fungal infection) due to its effect on the immune system. It has been used successfully in elderly patients and those with relapsed conditions, with some experiencing rapid symptom recovery and sustained remission.14678

How is the drug combination of Copanlisib and Ibrutinib unique for treating central nervous system lymphoma?

The combination of Copanlisib and Ibrutinib is unique because Ibrutinib is a Bruton's tyrosine kinase inhibitor that can cross the blood-brain barrier, offering a targeted approach for central nervous system lymphoma, which is a rare and aggressive cancer with limited standard treatment options. This combination may provide a novel therapeutic strategy, especially for patients who are not suitable for traditional chemotherapy.12349

What is the purpose of this trial?

This trial is testing the safety of using two drugs, copanlisib and ibrutinib, together. The study focuses on patients with a type of brain and spinal cord cancer called PCNSL. These drugs work by blocking proteins that cancer cells need to grow.

Research Team

Christian Grommes, MD - MSK Neuro ...

Christian Grommes, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Eligibility Criteria

Adults with primary central nervous system lymphoma (PCNSL) that's come back or hasn't responded to treatment, or those newly diagnosed but can't have standard chemo. They must be able to handle MRI/CT scans and lumbar punctures, have a life expectancy over 3 months, and good organ function. Contraception is required during the study.

Inclusion Criteria

- Absolute neutrophil count (ANC) ≥ 1.5 x 10^9/L
My kidney function, measured by creatinine, is within normal limits.
- International Normalized Ratio (INR) ≤ 1.5 and PTT (aPTT) ≤ 1.5 times the upper limit of normal
See 20 more

Exclusion Criteria

I have been newly diagnosed with primary CNS lymphoma and can receive methotrexate chemotherapy.
I have previously been treated with a PI3K, AKT, or mTOR inhibitor, but ibrutinib is allowed.
My high blood pressure is not controlled, even with medication.
See 25 more

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment Phase Ib

Participants receive Ibrutinib and Copanlisib to determine the maximum tolerated dose using a '3+3' design

1 year
Weekly visits for drug administration and monitoring

Treatment Phase II

Participants receive sequential drug dosing with Ibrutinib and Copanlisib in 28-day cycles

1 year
Weekly visits for drug administration and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 years

Treatment Details

Interventions

  • Copanlisib
  • Ibrutinib
Trial Overview The trial tests the safety of combining two drugs, copanlisib and ibrutinib, for treating PCNSL. Participants will receive both medications in an effort to determine how well they work together against this type of lymphoma.
Participant Groups
1Treatment groups
Experimental Treatment
Group I: Copanlisib in combination with IbrutinibExperimental Treatment2 Interventions
Participants will be assigned to the following dose levels: Dose level 1: Ibrutinib 560 mg daily + Copanlisib 60 mg weekly (3w on/1w off) Dose level 2: Ibrutinib 840 mg daily + Copanlisib 60 mg weekly (3w on/1w off) Dose level -1: Ibrutinib 560 mg daily + Copanlisib 45 mg weekly (3w on/1w off). Phase II: (Simon two-stage design: 14 patients will be treated at the MTD (including 6 patients from the phaseIb portion) If at least 11 patients respond then an additional 19 patients will be accrued to the second stage. Patients in the phase II portion of the trial will receive sequential drug dosing. Patient will be treated in 28-day cycles. During one cycle, only one drug will be administered with a ibrutinib/copanlisib ratio of 1:2. Patients will receive Ibrutinib at 840 mg daily during cycle 1 (day 1 through day 28) (28-day cycles), then copanlisib 60mg weekly on day 1, 8, and 15 during cycle 2 and 3. Patients will then repeat the sequence.

Find a Clinic Near You

Who Is Running the Clinical Trial?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials
1,998
Recruited
602,000+

Findings from Research

A 77-year-old patient with primary central nervous system lymphoma (PCNSL) showed good tolerance and sustained remission after receiving ibrutinib as a consolidation therapy following high-dose methotrexate and rituximab plus temozolomide.
This case suggests that ibrutinib, a Bruton's tyrosine kinase inhibitor that can cross the blood-brain barrier, may be an effective option for elderly patients with PCNSL, but further studies are needed to confirm these findings.
Successful Consolidation/Maintenance Therapy with Single Agent Ibrutinib for Primary CNS Lymphoma after Initial Induction Therapy.Du, S., Bota, D., Kong, XT.[2022]
Ibrutinib showed promising efficacy in treating relapsed/refractory primary and secondary central nervous system lymphomas, with an objective response rate of 58% and a complete response rate of 55% among 33 patients studied.
The treatment resulted in a median progression-free survival of 3.1 months for primary CNS lymphoma and 10.2 months for secondary CNS lymphoma, with only one case of invasive fungal infection reported, indicating a favorable safety profile despite concurrent steroid use.
Ibrutinib for central nervous system lymphoma: the Australasian Lymphoma Alliance/MD Anderson Cancer Center experience.Lewis, KL., Chin, CK., Manos, K., et al.[2021]
In a retrospective study of patients with primary central nervous system lymphoma (PCNSL), three patients showed good clinical responses to ibrutinib-based therapy, indicating its potential effectiveness in treating this aggressive cancer, especially in those unfit for traditional chemotherapy.
In vitro and pharmacokinetic studies revealed that ibrutinib demonstrated the strongest anti-tumoral effects compared to other BTK inhibitors, and both ibrutinib and tirabrutinib effectively penetrated the blood-brain barrier, making them promising candidates for targeted therapy in PCNSL.
Bruton's tyrosine kinase inhibitors in primary central nervous system lymphoma-evaluation of anti-tumor efficacy and brain distribution.Yu, H., Kong, H., Li, C., et al.[2022]

References

Successful Consolidation/Maintenance Therapy with Single Agent Ibrutinib for Primary CNS Lymphoma after Initial Induction Therapy. [2022]
Ibrutinib for central nervous system lymphoma: the Australasian Lymphoma Alliance/MD Anderson Cancer Center experience. [2021]
Ibrutinib improves survival compared with chemotherapy in mantle cell lymphoma with central nervous system relapse. [2023]
Bruton's tyrosine kinase inhibitors in primary central nervous system lymphoma-evaluation of anti-tumor efficacy and brain distribution. [2022]
Spotlight on Ibrutinib in PCNSL: Adding Another Feather to Its Cap. [2021]
Activity of ibrutinib in mantle cell lymphoma patients with central nervous system relapse. [2021]
Inhibition of B Cell Receptor Signaling by Ibrutinib in Primary CNS Lymphoma. [2022]
Rituximab-Lenalidomide-Ibrutinib Combination for Relapsed/Refractory Primary CNS Lymphoma: A Case Series of the LOC Network. [2021]
The outcome of ibrutinib-based regimens in relapsed/refractory central nervous system lymphoma and the potential impact of genomic variants. [2023]
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