Copanlisib With Dose-Adjusted EPOCH-R in Relapsed and Refractory Burkitt Lymphoma and Other High-Grade B-cell Lymphomas
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- STATUS
- Recruiting
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- End date
- Jul 1, 2025
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- participants needed
- 34
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- sponsor
- National Cancer Institute (NCI)
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.
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 lymphomasdouble 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 34
Details
| Condition | 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) |
|---|---|
| Treatment | Rituximab, cyclophosphamide, etoposide, prednisone, vincristine, doxorubicin, Copanlisib |
| Clinical Study Identifier | NCT04933617 |
| Sponsor | National Cancer Institute (NCI) |
| Last Modified on | 19 June 2022 |
Eligibility
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