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

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 dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab (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 diffuse large B-cell lymphoma (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.

Conditions

• Burkitt Lymphoma
• High-grade B-cell Lymphoma
• T-cell/Histocyte-rich Large B-cell Lymphoma
• Diffuse Large B-Cell Lymphoma (DLBCL)
• Germinal Center B-cell Type (GCB)

Interventions

BIOLOGICAL

Rituximab

Rituximab 375 mg/m\^2 intravenous (IV) per protocol on Day 1 of each cycle up to 6 cycles

DRUG

Etoposide

Etoposide 50 mg/m\^2/day continuous intravenous infusion (CIVI) on Days 1-4 of each cycle up to 6 cycles

BIOLOGICAL

Copanlisib

Copanlisib intravenous (IV) is administered at a fixed dose (30 mg, 45 mg, or 60 mg) on days 1 and 5 of each 21-day cycle for up to 6 cycles

DRUG

Cyclophosphamide

Cyclophosphamide 750 mg/m\^2 intravenous (IV) on Day 5 of each cycle up to 6 cycles

DRUG

Doxorubicin

Doxorubicin 10 mg/m\^2/day continuous intravenous infusion (CIVI) on Days 1-4 of each cycle up to 6 cycles

DRUG

Vincristine

Vincristine 0.4 mg/m\^2/day (no cap) continuous intravenous infusion (CIVI) on Days 1-4 of each cycle up to 6 cycles

DRUG

Prednisone

Prednisone 60 mg/m\^2 by mouth (PO) twice a day (BID) Days 1-5 (total 120mg/m\^2/day)

DIAGNOSTIC_TEST

ECHO

At screening.

DIAGNOSTIC_TEST

EKG

At screening.

DIAGNOSTIC_TEST

MRI Brain

At screening.

DIAGNOSTIC_TEST

18F-FDG - PET

At screening, baseline, after cycle 1, 3, and 6, and end of treatment.

DIAGNOSTIC_TEST

CT Scan

At screening, baseline, after cycle 1, 3, and 6, end of treatment and follow-up.

PROCEDURE

Bone Marrow Aspiration

At screening and end of treatment.

PROCEDURE

Bone Marrow Biopsy

At screening and end of treatment.

DIAGNOSTIC_TEST

Lumbar Puncture (LP)

Baseline and end of treatment.

Sponsors & Collaborators

• National Cancer Institute (NCI)

  lead NIH

Principal Investigators

• Mark J Roschewski, M.D. · National Cancer Institute (NCI)

Study Design

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

SEQUENTIAL

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2022-03-24

Primary Completion

2023-11-30

Completion

2023-11-30

FDA Drug

Yes

Countries

• United States

Study Locations