Trials / Terminated

TerminatedNCT04933617

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

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

Status: Terminated
Phase: Phase 1
Study type: Interventional
Enrollment: 8 (actual)

Sponsor: National Cancer Institute (NCI) · NIH
Sex: All
Age: 18 Years
Healthy volunteers: Not accepted

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.

Detailed 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 myelocytomatosis (MYC) gene rearrangement as well as those that have transformed from an underlying indolent lymphoma have a lower cure rate. Dose-adjusted dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab (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 myelocytomatosis (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 follicular lymphoma (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, National Cancer Institute (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, not otherwise specified (NOS), High-grade B-cell lymphoma, with MYC and B-cell lymphoma 2 (BCL2) and/or B-cell lymphoma 6 (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 Eastern Cooperative Oncology Group (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 recommended phase 2 dose (RP2D) and maximum tolerated dose (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.

Conditions

Interventions

Type	Name	Description
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.

Timeline

Start date: 2022-03-24
Primary completion: 2023-11-30
Completion: 2023-11-30
First posted: 2021-06-22
Last updated: 2024-07-09
Results posted: 2024-07-09

Locations

1 site across 1 country: United States

Regulatory

FDA-regulated drug study

Source: ClinicalTrials.gov record NCT04933617. Inclusion in this directory is not an endorsement.