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Protocol Details

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

This study is NOT currently recruiting participants.

Summary | Eligibility | Citations | Contacts




Sponsoring Institute

National Cancer Institute (NCI)

Recruitment Detail

Type: Completed Study; data analyses ongoing
Gender: Male & Female
Min Age: 18 Years
Max Age: N/A

Referral Letter Required


Population Exclusion(s)

Pregnant Women;


BAY 80-6946;
Monoclonal Antibody;
PI3K Target

Recruitment Keyword(s)



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)

Investigational Drug(s)


Investigational Device(s)



Biological/Vaccine: Rituximab
Drug: Etoposide
Biological/Vaccine: Copanlisib
Drug: Cyclophosphamide
Drug: Doxorubicin
Drug: Vincristine
Drug: Prednisone
Diagnostic Test: ECHO
Diagnostic Test: EKG
Diagnostic Test: MRI Brain
Diagnostic Test: 18F-FDG - PET
Diagnostic Test: CT Scan
Procedure/Surgery: Bone Marrow Aspiration
Procedure/Surgery: Bone Marrow Biopsy
Diagnostic Test: Lumbar Puncture (LP)

Supporting Site

National Cancer Institute


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.


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).


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).


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.

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

--At least 1 anthracycline-containing regimen:

---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


--Must have had at least 2 prior regimens, 1 of which must have been anthracyclinecontaining regimen OR be primary refractory to frontline therapy:

---DLBCL, NOS, Germinal center B-cell type (GCB) type;

NOTE: subjects with coexisting or a history of indolent lymphoma are eligible (i.e., transformed lymphoma )

---T-cell/histocyte-rich large B-cell lymphoma

-Measurable or evaluable disease on imaging scans or bone marrow

-No other current systemic anti-lymphoma therapy. NOTE: Recent short-term (less than or equal to 7 days) use of corticosteroids or prior radiation to sites of disease involvement is permitted.

-Any human immunodeficiency virus (HIV) status will be included in this study as long as infection is controlled; in the opinion of the investigator. Status must be confirmed at screening and the subject must be willing to take any recommended antiretroviral therapy.

-Greater than or equal to 18 years of age on day of signing informed consent

-Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to 2

-Adequate organ function as evidenced by the following laboratory parameters, unless dysfunction is secondary to lymphoma involvement as determined by the investigator:

--Absolute neutrophil count (ANC) greater than or equal to 1,000/mm^3

--Platelets greater than or equal to 100 x 10^9 /L

--Hemoglobin greater than or equal to 8 g/dL (unless due to disease itself, transfusion permitted to meet criteria)

--Renal function Glomerular filtration rate (GFR) greater than or equal to 50ml/min/1.73 m^2 as estimated by Modification of Diet in Renal Disease (MDRD) abbreviated formula. If not on target, a 24- hour urine creatinine clearance can be used to directly measure.

--Total bilirubin less than or equal to 1.5 x ULN OR < 1.5-3.0 x ULN for subjects with liver involvement*

--Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) less than or equal to 3.0 x ULN OR < 5 x ULN for subjects with liver involvement

*Acceptable range as long as there is no persistent nausea, vomiting, right upper quadrant pain or tenderness, fever, rash, or eosinophilia

-Must have fully recovered from all effects of prior surgery. NOTE: Minor procedures requiring Twilight sedation, such as tissue biopsies, endoscopies or mediport placement require a 24-hour waiting period prior to treatment initiation.

-Women of childbearing potential (WOCBP) and men with female partners of childbearing potential must agree to use a highly effective method of contraception when sexually active (intrauterine device, surgical sterilization, contraceptive rod, abstinence) for the time period between signing of the informed consent form and for at least 1 month after the last dose of copanlisib. WOCBP and men with female partners of childbearing potential must agree to use an effective method of contraception (two of the following: diaphragm, cervical cap, contraceptive sponge, condom, hormonal) when sexually active for the time period between signing of the informed consent and for at least 12 months after the last dose of rituximab. Women of childbearing potential must have a serum pregnancy test performed a maximum of 7 days before start of treatment, and a negative result must be documented before start of treatment.

NOTE: A woman is considered of childbearing potential, (i.e., fertile), following menarche and until becoming post-menopausal unless permanently sterile. Permanent sterilization methods include but are not limited to hysterectomy, bilateral salpingectomy and bilateral oophorectomy. A postmenopausal state is defined as no menses for continuous 12 months without an alternative medical cause. A high follicle stimulating hormone (FSH) level in the postmenopausal range may be used to confirm a postmenopausal state in women not using hormonal contraception or hormonal replacement therapy. The investigator or a designated associate is requested to advise the subject how to achieve highly effective birth control (failure rate of less than 1%), e.g., intrauterine device (IUD), intrauterine hormone-releasing system (IUS), bilateral tubal occlusion, asectomized partner and sexual abstinence.

-Willingness to have a central venous access line placed if the subject does not already have one in place

-Ability of patient to understand and the willingness to sign a written informed consent document


-Subjects previously exposed to, intolerant of, or ineligible for phosphoinositide 3-kinases (PI3K) inhibitors and/or their combination

-Brain parenchymal involvement

-Patients who have been treated with prior chimeric antigen receptor (CAR)-T therapy or any regimen containing fludarabine.

-Cytomegalovirus (CMV)-positive polymerase chain reaction (PCR) at screening

-History of diabetic ketoacidosis

-Uncontrolled intercurrent illness including, but not limited to the following that may limit interpretation of results or that could increase risk to the subject at the discretion of the investigator:

--Any secondary malignancy that requires active systemic therapy

--Diabetes mellitus with hemoglobin (Hgb) hemoglobin A1C (A1C) > 8.5

--Clinically significant interstitial lung disease and/or lung disease that severly impairs lung function

--Uncontrolled human immunodeficiency virus (HIV)

--Active hepatitis C infection. NOTE: Subjects who are hepatitis C antibody positive will need to have a negative hepatitis C virus (HCV) PCR result before enrollment. Those with a positive PCR for hepatitis C are excluded.

--Active hepatitis B infection. NOTE: Patients who are hepatitis B surface antigen (HbsAg) or hepatitis B core antibody (HbcAb) positive will need to have a negative HBV PCR result before enrollment. Those with a positive PCR for hepatitis B are excluded. Those who are hepatitis B surface antigen (HbsAg) or hepatitis B core antibody (HbcAb) positive with a negative PCR for hepatitis B will be treated with antivirals designed to prevent hepatitis B reactivation (e.g., entecavir) throughout therapy and for 12 months after therapy and have monitoring for hepatitis B reactivation with PCR.

--Clinically significant, uncontrolled heart disease and/or cardiac repolarization abnormalities, including any of the following:

---History of acute coronary syndromes (including myocardial infarction, unstable angina, coronary artery bypass grafting, coronary angioplasty, or stenting) or symptomatic pericarditis within 6 months prior to screening

---Congestive heart failure (New York Heart Association functional classification III-IV)

---Unstable angina

---Left Ventricular Ejection Fraction (LVEF) <40% as determined by echocardiogram (ECHO) at screening

---Clinically significant cardiac arrhythmias (e.g., ventricular tachycardia), complete left bundle branch block, high-grade AV block (e.g., bifascicular block, Mobitz type II and third-degree AV block)

---Long QT syndrome or family history of idiopathic sudden death or congenital long QT syndrome, or any of the following:

----Long QT syndrome or family history of idiopathic sudden death or congenital long QT syndrome, or any of the following:

----Inability to determine the QT interval on screening (QTcF, using Fredericia s correction)

----Long QT syndrome or family history of idiopathic sudden death or congenital long QT syndrome

--Known mental or physical illness that would interfere with cooperation with the requirements of the trial or confound the results or interpretation of the results of the trial and, in the opinion of the treating investigator, would make the subject inappropriate for entry into the study.

-Requirement to continue on any of the medications that are excluded

-Breast-feeding subjects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with these agents, breastfeeding should be discontinued if the mother is treated on study.

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Not Provided

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Principal Investigator

Referral Contact

For more information:

Mark J. Roschewski, M.D.
National Cancer Institute (NCI)
(240) 760-6183

NCI Medical Oncology Referral Office
National Cancer Institute (NCI)

(888) 624-1937

NCI Referral Office
National Institute of Health Clinical Center (CC), 9000 Rockville Pike, Bethesda, Maryland 20892, United States: NCI Clinical Trials Referral Office

Clinical Trials Number:


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