Copanlisib With Dose-Adjusted EPOCH-R in Relapsed and Refractory Burkitt Lymphoma and Other High-Grade B-cell Lymphomas

Burkitt Lymphoma Clinical Trial

Official title: Phase 1 Study of Copanlisib With Dose-adjusted EPOCH-R in Relapsed and Refractory Burkitt Lymphoma and Other High-Grade B-cell Lymphomas

Status Completed

Clinical Trial Summary

Background:

Burkitt Lymphoma (BL) and diffuse large B-cell lymphoma (DLBCL) are aggressive B cell lymphomas. Frontline treatment does not always work. Researchers want to see if a combination of drugs can help.

Objective:

To learn if it is safe to give people with certain cancers copanlisib together with rituximab and combination chemotherapy (DA-EPOCH-R).

Eligibility:

People ages 18 and older with relapsed and/or refractory highly aggressive B-cell lymphomas such as BL and certain types of DLBCL.

Design:

Participants will be screened with:

Medical history

Physical exam

Bone marrow aspiration and biopsy. A needle will be put into their hipbone. Marrow will be removed.

Imaging scans of the chest, abdomen, pelvis, and/or brain

Tumor biopsy (if needed)

Blood and urine tests

Heart function tests

Treatment will be given in 21-day cycles for up to 6 cycles. Participants will get copanlisib by intravenous (IV) infusion. They will also get a group of medicines called DA-EPOCH-R, as follows. They will get rituximab by IV infusion. Doxorubicin, etoposide, and vincristine will be mixed together in an IV bag and given by continuous IV infusion over 4 days. They will get cyclophosphamide by IV infusion. They will take prednisone by mouth.

Participants will have frequent study visits. At these visits, they will repeat some screening tests. They may give tissue, saliva, and cheek swab samples. They will have at least one spinal tap. For this, a needle will be inserted into the spinal canal. Fluid will be removed.

Participants will have a visit 30 days after treatment ends. They will have follow-up visits for at least 5 years.

Clinical Trial Description

Background:

Burkitt Lymphoma (BL) is a highly aggressive B cell lymphoma that often involves the bone marrow and central nervous system (CNS)

Frontline therapy cures 80-85% of adults with BL but patients with CNS involvement or those who relapse after frontline therapy are at high risk for treatment failure

Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous group of aggressive B-cell lymphomas that are successfully cured by frontline therapy in 60-70% of cases

A subset of DLBCL that have MYC gene rearrangement as well as those that have transformed from an underlying indolent lymphoma have a lower cure rate

Dose-adjusted (DA)-EPOCH-R is an infusional chemotherapy platform often used as frontline therapy for these aggressive B-cell lymphomas and is an effective chemotherapy platform from which to rationally design novel therapies for patients with BL, high grade B-cell lymphomas- double hit/triple hit (HGBCL-DH/TH), DLBCL and MYC rearrangements, and other high-risk DLBCL

The phosphoinositide 3-kinase (PI3K) pathway is an important signaling pathway for cellular responses to growth factors and a downstream event of B-cell receptor signaling.

Copanlisib targets both PI3K-a and PI3K-d isoforms and is approved for relapsed FL, active as monotherapy in DLBCL, and highly effective in pre-clinical models of BL

Copanlisib crosses the blood brain barrier suggesting it may prevent secondary CNS spread in highly aggressive B-cell lymphomas.

Copanlisib is a rational targeted agent to be added to DA-EPOCH-R in patients with BL, HGBCL-DH/TH, and other high-risk B-cell lymphomas.

Objective:

To determine the Maximal tolerated dose (MTD) and Recommended Phase II dose (RP2D) of copanlisib in combination with DA-EPOCH-R in subjects with Burkitt lymphoma (BL) and high grade B-cell lymphomas- double hit/triple hit (HGBCL-DH/TH) relapsed after or refractory to chemo-immunotherapy

Eligibility:

Subjects must have a histologic diagnosis, confirmed by the Laboratory of Pathology, NCI with one of the following subtypes and prior therapy, as follows:

Burkitt lymphoma, Burkitt-like lymphoma with 11q aberration, High-grade B-cell lymphoma, NOS, High-grade B-cell lymphoma, with MYC and BCL2 and/or BCL6 rearrangements - following at least 1 anthracycline-containing regimen

OR

DLBCL, NOS, Germinal center B-cell type (GCB) type, T-cell/histocyte-rich large B-cell lymphoma, following at least 1 anthracycline-containing regimen AND at least 2 prior regimens OR be primary refractory to frontline therapy

Age >= 18

ECOG performance status 0-2

Adequate bone marrow and organ function

Design:

Phase 1, open-label, single center, non-randomized

"3+3" dosing will be used to determine the RP2D and MTD of dose escalated copanlisib in combination with standard regimen DA-EPOCH-R

Maximum 6 cycles (21-day cycles) of combination therapy

Dose expansion at the RP2D or MTD to evaluate efficacy and further evaluate safety

To explore all dose levels, including further evaluation in dose expansion cohort, the accrual ceiling will be set at 39 ;

Related Conditions & MeSH terms

• Burkitt Lymphoma
• Diffuse Large B-Cell Lymphoma (DLBCL)
• High-grade B-cell Lymphoma
• Lymphoma
• Lymphoma, B-Cell
• Lymphoma, Large B-Cell, Diffuse

• NCT number: NCT04933617
• Study type: Interventional
• Source: National Institutes of Health Clinical Center (CC)
• Status: Completed
• Phase: Phase 1
• Start date: March 24, 2022
• Completion date: November 30, 2023