Copanlisib + Ibrutinib for Central Nervous System Lymphoma

Recruiting in Palo Alto (17 mi)

+8 other locations

Overseen byChristian Grommes, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1 & 2

Waitlist Available

Sponsor: Memorial Sloan Kettering Cancer Center

No Placebo Group

Breakthrough Therapy

Trial Summary

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.

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

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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.

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Treatment Details

Interventions

Copanlisib (PI3K inhibitor)
Ibrutinib (BTK inhibitor)

Trial OverviewThe 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.