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| ID | Type | Description | Link |
|---|---|---|---|
| 000193-C |
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The study was terminated early because copanlisib was removed from the market by the Food and Drug Administration (FDA) and the manufacturer.
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Arm 1- Dose Escalation, Original Copanlisib Intravenous (IV) | Experimental | Copanlisib intravenous (IV) per dose level (30 mg, 45 mg, or 60 mg) on day 1 of each 21-day cycle in combination with standard dosing dose adjusted rituximab, etoposide, prednisolone, vincristine, cyclophosphamide, doxorubicin (DA-EPOCH-R) to determine recommended phase 2 dose (RP2D) and maximum tolerated dose (MTD) of copanlisib. Up to 6 cycles total. |
|
| Arm 2 - Dose Expansion, Modified Copanlisib Intravenous (IV) | Experimental | Copanlisib intravenous (IV) at the recommended phase 2 dose (RP2D) or maximum tolerated dose (MTD) on day 1 of each 21-day cycle in combination with standard dosing dose adjusted rituximab, etoposide, prednisolone, vincristine, cyclophosphamide, doxorubicin (DA-EPOCH-R). Up to 6 cycles total. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Rituximab | Biological | Rituximab 375 mg/m^2 intravenous (IV) per protocol on Day 1 of each cycle up to 6 cycles |
|
| Measure | Description | Time Frame |
|---|---|---|
| Maximum Tolerated Dose (MTD) and Recommended Phase II Dose (RP2D) | MTD and RP2D is defined as the dose level at which no more than 1 of up to 6 participants experience dose limiting toxicity (DLT) during the DLT period, and the dose below that at which at least 2 (of ≤6) participants have DLT as a result of treatment. A DLT is any treatment-emergent, clinically relevant, and related severe (grade ≥ 3) toxicity that is possibly, probably, or definitely related to copanlisib. | 21 days |
| Measure | Description | Time Frame |
|---|---|---|
| Overall Response Rate (ORR) | ORR is the best response recorded from the start of the treatment until disease progression/recurrence determined by Kaplan-Meier method and reported along with a 95% confidence interval. Response was assessed by the Revised Response Criteria for Malignant Lymphoma criteria, and the Lugano Classification Response Criteria for Non-Hodgkin Lymphoma (NHL). Complete response (CR) is complete disappearance of all detectable evidence of disease and disease-related symptoms. Partial response (PR) is a ≥50% decrease in the sum of the product of the diameters of up to 6 of the largest dominant nodes or nodal masses. Progressive disease (PD) is appearance of any new nodal lesion ≥1.6 cm in greatest tumor dimension or ≥1.1 cm in short axis during or after the end of therapy. A participant is considered to have stable disease (SD) when he or she fails to attain the criteria needed for a CR, PR, or Minimal Response (MR) but does not fulfill those for PD. |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Serious and/or Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0) | Here is the number of participants with serious and/or non-serious adverse events assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life-threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned. |
INCLUSION CRITERIA:
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:
At least 1 anthracycline-containing regimen:
OR
--Must have had at least 2 prior regimens, 1 of which must have been anthracycline containing regimen OR be primary refractory to frontline therapy:
---Diffuse large B-cell lymphoma (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:
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 upper limit of normal (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.
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, vasectomized partner and sexual abstinence.
EXCLUSION CRITERIA:
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 severely 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 atrioventricular (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:
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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| Name | Affiliation | Role |
|---|---|---|
| Mark J Roschewski, M.D. | National Cancer Institute (NCI) | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| National Institutes of Health Clinical Center | Bethesda | Maryland | 20892 | United States |
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| Label | URL |
|---|---|
| NIH Clinical Center Detailed Web Page | View source |
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All individual participant data (IPD) recorded in the medical record will be shared with intramural investigators upon request. All large- scale genomic sequencing data will be shared with subscribers to the database of Genotypes and Phenotypes (dbGaP).
Clinical data available during the study and indefinitely. Genomic data are available once genomic data are uploaded per protocol Genomic Data Sharing (GDS) plan for as long as database is active.
Clinical data will be made available via subscription to Biomedical Translational Research Information System (BTRIS) and with the permission of the study principal investigator (PI). Genomic data are made available via the database of Genotypes and Phenotypes (dbGaP) through requests to the data custodians.
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| ID | Title | Description |
|---|---|---|
| FG000 | Dose Escalation: Arm 1, Dose Level 1, Original: 30mg Copanlisib | Copanlisib intravenous (IV) per dose level (30 mg) on day 1 of each 21-day cycle in combination with standard dosing dose adjusted rituximab, etoposide, prednisolone, vincristine, cyclophosphamide, doxorubicin (DA-EPOCH-R) to determine recommended phase 2 dose (RP2D) and maximum tolerated dose (MTD) of copanlisib. Up to 6 cycles total. Rituximab: Rituximab 375 mg/m^2 intravenous (IV) per protocol on Day 1 of each cycle up to 6 cycles Etoposide: Etoposide 50 mg/m^2/day continuous intravenous infusion (CIVI) on Days 1-4 of each cycle up to 6 cycles Copanlisib: Copanlisib intravenous 30mg intravenous (IV) on days 1 and 5 of each 21-day cycle for up to 6 cycles Cyclophosphamide: Cyclophosphamide 750 mg/m^2 intravenous (IV) on Day 5 of each cycle up to 6 cycles Doxorubicin: Doxorubicin 10 mg/m^2/day continuous intravenous infusion (CIVI) on Days 1-4 of each cycle up to 6 cycles 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 Prednisone: Prednisone 60 mg/m^2 by mouth (PO) twice a day (BID) Days 1-5 (total 120mg/m^2/day) |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Dose Escalation |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Apr 24, 2023 |
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| Etoposide | Drug | Etoposide 50 mg/m^2/day continuous intravenous infusion (CIVI) on Days 1-4 of each cycle up to 6 cycles |
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| Copanlisib | Biological | 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 |
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| Cyclophosphamide | Drug | Cyclophosphamide 750 mg/m^2 intravenous (IV) on Day 5 of each cycle up to 6 cycles |
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| Doxorubicin | Drug | Doxorubicin 10 mg/m^2/day continuous intravenous infusion (CIVI) on Days 1-4 of each cycle up to 6 cycles |
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| Vincristine | Drug | Vincristine 0.4 mg/m^2/day (no cap) continuous intravenous infusion (CIVI) on Days 1-4 of each cycle up to 6 cycles |
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| Prednisone | Drug | Prednisone 60 mg/m^2 by mouth (PO) twice a day (BID) Days 1-5 (total 120mg/m^2/day) |
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| ECHO | Diagnostic Test | At screening. |
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| EKG | Diagnostic Test | At screening. |
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| MRI Brain | Diagnostic Test | At screening. |
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| 18F-FDG - PET | Diagnostic Test | At screening, baseline, after cycle 1, 3, and 6, and end of treatment. |
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| CT Scan | Diagnostic Test | At screening, baseline, after cycle 1, 3, and 6, end of treatment and follow-up. |
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| Bone Marrow Aspiration | Procedure | At screening and end of treatment. |
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| Bone Marrow Biopsy | Procedure | At screening and end of treatment. |
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| Lumbar Puncture (LP) | Diagnostic Test | Baseline and end of treatment. |
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| Response was assessed after cycles 1, 3 and 6 (each cycle is 21 days), approximately 63 days. |
| Progression-free Survival (PFS) | PFS is defined as the time from date of study enrollment until time of disease relapse, disease progression, or death, whichever occurs first, assessed every 3-6 months The progression free survival will be determined by the Kaplan-Meier method and reported along with a 95% confidence interval. Response was assessed by the Revised Response Criteria for Malignant Lymphoma criteria, and the Lugano Classification Response Criteria for Non-Hodgkin Lymphoma (NHL). Disease relapse is Progressive disease (PD) is appearance of any new nodal lesion ≥1.6 cm in greatest tumor dimension or ≥1.1 cm in short axis during or after the end of therapy or increase by ≥50% from PPD (cross product of the longest transverse diameter and perpendicular diameter) nadir. | Time from enrollment to progression or death, approximately 9 months. |
| Complete Response Rate | Response was assessed by the Revised Response Criteria for Malignant Lymphoma criteria, and the Lugano Classification Response Criteria for Non-Hodgkin Lymphoma (NHL). Complete response (CR) is complete disappearance of all detectable evidence of disease and disease-related symptoms. The response rate will be determined by Kaplan-Meier method and reported along with a 95% confidence interval. | Response was assessed after cycles 1, 3 and 6 (each cycle is 21 days). Approximately 63 days. |
| Overall Survival (OS) | OS is defined as the time from the date of study enrollment until death from any cause, assessed every 3-6 months. OS will be determined by the Kaplan-Meier method and reported along with a 95% confidence interval. | Time from enrollment to death, approximately 1 year |
| Event-free Survival (EFS) | EFS is defined as the time from the date of study enrollment until time of disease relapse from complete response (CR), disease progression, initiation of subsequent systemic anti-lymphoma therapy for either positron-emission tomography (PET)-positive or biopsy-proven residual disease, or death, whichever occurs first. The EFS will be determined by the Kaplan-Meier method and reported along with a 95% confidence interval. Response was assessed by the Revised Response Criteria for Malignant Lymphoma criteria, and the Lugano Classification Response Criteria for Non-Hodgkin Lymphoma (NHL). Complete response (CR) is complete disappearance of all detectable evidence of disease and disease-related symptoms. Progressive disease (PD) is appearance of any new nodal lesion ≥1.6 cm in greatest tumor dimension or ≥1.1 cm in short axis during or after the end of therapy. Disease relapse is Progressive disease (PD), an appearance of any new nodal lesion ≥1.6 cm in greatest tumor dimension. | Time from enrollment to next line of anti-lymphoma therapy, progressive disease, or death. Approximately 6 months. |
| Number of Serious and/or Non-serious Grades 3-5 Adverse Events Related to Copanlisib | Rate and severity of adverse events (AEs) summarized by grade and type of toxicity. AE's were assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life-threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned. Grade 3 is severe. Grade 4 is life-threatening. Grade 5 is death related to adverse event. | An average of 245.5 days |
| Date treatment consent signed to date off study, an average of 245.5 days |
| Number of Participants With Dose Limiting-toxicity (DLT) | A DLT is any treatment-emergent, clinically relevant, and related severe (grade ≥ 3) toxicity that is possibly, probably or definitely related to copanlisib. | 21 days |
| FG001 | Dose Escalation: Arm 1, Dose Level 1, Modified: 30mg Copanlisib | Copanlisib intravenous (IV) per dose level (30 mg) on day 1 of each 21-day cycle in combination with standard dosing dose adjusted rituximab, etoposide, prednisolone, vincristine, cyclophosphamide, doxorubicin (DA-EPOCH-R) to determine recommended phase 2 dose (RP2D) and maximum tolerated dose (MTD) of copanlisib. Up to 6 cycles total. Rituximab: Rituximab 375 mg/m^2 intravenous (IV) per protocol on Day 1 of each cycle up to 6 cycles Etoposide: Etoposide 50 mg/m^2/day continuous intravenous infusion (CIVI) on Days 1-4 of each cycle up to 6 cycles Copanlisib: Copanlisib intravenous 30mg intravenous (IV) on day 1 of each 21-day cycle for up to 6 cycles Cyclophosphamide: Cyclophosphamide 750 mg/m^2 intravenous (IV) on Day 5 of each cycle up to 6 cycles Doxorubicin: Doxorubicin 10 mg/m^2/day continuous intravenous infusion (CIVI) on Days 1-4 of each cycle up to 6 cycles 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 Prednisone: Prednisone 60 mg/m^2 by mouth (PO) twice a day (BID) Days 1-5 (total 120mg/m^2/day) |
| FG002 | Dose Escalation: Arm 1, Dose Level 2, Original: 45mg Copanlisib | Copanlisib intravenous (IV) per dose level (45 mg) on day 1 of each 21-day cycle in combination with standard dosing dose adjusted rituximab, etoposide, prednisolone, vincristine, cyclophosphamide, doxorubicin (DA-EPOCH-R) to determine recommended phase 2 dose (RP2D) and maximum tolerated dose (MTD) of copanlisib. Up to 6 cycles total. Rituximab: Rituximab 375 mg/m^2 intravenous (IV) per protocol on Day 1 of each cycle up to 6 cycles Etoposide: Etoposide 50 mg/m^2/day continuous intravenous infusion (CIVI) on Days 1-4 of each cycle up to 6 cycles Copanlisib: Copanlisib intravenous 45mg intravenous (IV) on day 1 of each 21-day cycle for up to 6 cycles Cyclophosphamide: Cyclophosphamide 750 mg/m^2 intravenous (IV) on Day 5 of each cycle up to 6 cycles Doxorubicin: Doxorubicin 10 mg/m^2/day continuous intravenous infusion (CIVI) on Days 1-4 of each cycle up to 6 cycles 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 Prednisone: Prednisone 60 mg/m^2 by mouth (PO) twice a day (BID) Days 1-5 (total 120mg/m^2/day) |
| FG003 | Dose Escalation: Arm 1, Dose Level 1, Modified: 60mg Copanlisib | Copanlisib intravenous (IV) per dose level (60 mg) on day 1 of each 21-day cycle in combination with standard dosing dose adjusted rituximab, etoposide, prednisolone, vincristine, cyclophosphamide, doxorubicin (DA-EPOCH-R) to determine recommended phase 2 dose (RP2D) and maximum tolerated dose (MTD) of copanlisib. Up to 6 cycles total. Rituximab: Rituximab 375 mg/m^2 intravenous (IV) per protocol on Day 1 of each cycle up to 6 cycles Etoposide: Etoposide 50 mg/m^2/day continuous intravenous infusion (CIVI) on Days 1-4 of each cycle up to 6 cycles Copanlisib: Copanlisib intravenous 60mg intravenous (IV) on day 1 of each 21-day cycle for up to 6 cycles Cyclophosphamide: Cyclophosphamide 750 mg/m^2 intravenous (IV) on Day 5 of each cycle up to 6 cycles Doxorubicin: Doxorubicin 10 mg/m^2/day continuous intravenous infusion (CIVI) on Days 1-4 of each cycle up to 6 cycles 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 Prednisone: Prednisone 60 mg/m^2 by mouth (PO) twice a day (BID) Days 1-5 (total 120mg/m^2/day) |
| FG004 | Arm 2 - Dose Expansion, Modified Copanlisib | Copanlisib intravenous (IV) at the recommended phase 2 dose (RP2D) or maximum tolerated dose (MTD) on day 1 of each 21-day cycle in combination with standard dosing dose adjusted rituximab, etoposide, prednisolone, vincristine, cyclophosphamide, doxorubicin (DA-EPOCH-R). Up to 6 cycles total. Rituximab: Rituximab 375 mg/m^2 intravenous (IV) per protocol on Day 1 of each cycle up to 6 cycles Etoposide: Etoposide 50 mg/m^2/day continuous intravenous infusion (CIVI) on Days 1-4 of each cycle up to 6 cycles Copanlisib: Copanlisib intravenous (IV) is administered at a fixed dose (30 mg, 45 mg, or 60 mg) on day 1 of each 21-day cycle for up to 6 cycles. Cyclophosphamide: Cyclophosphamide 750 mg/m^2 intravenous (IV) on Day 5 of each cycle up to 6 cycles Doxorubicin: Doxorubicin 10 mg/m^2/day continuous intravenous infusion (CIVI) on Days 1-4 of each cycle up to 6 cycles 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 Prednisone: Prednisone 60 mg/m^2 by mouth (PO) twice a day (BID) Days 1-5 (total 120mg/m^2/day) |
| COMPLETED |
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| NOT COMPLETED |
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| Dose Expansion |
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| ID | Title | Description |
|---|---|---|
| BG000 | Dose Escalation: Arm 1, Dose Level 1, Original: 30mg Copanlisib | Copanlisib intravenous (IV) per dose level (30 mg) on days 1 and 5 of each 21-day cycle in combination with standard dosing dose adjusted rituximab, etoposide, prednisolone, vincristine, cyclophosphamide, doxorubicin (DA-EPOCH-R) to determine recommended phase 2 dose (RP2D) and maximum tolerated dose (MTD) of copanlisib. Up to 6 cycles total. Rituximab: Rituximab 375 mg/m^2 intravenous (IV) per protocol on Day 1 of each cycle up to 6 cycles Etoposide: Etoposide 50 mg/m^2/day continuous intravenous infusion (CIVI) on Days 1-4 of each cycle up to 6 cycles Copanlisib: Copanlisib intravenous (IV) is administered at a fixed dose (30 mg) on days 1 and 5 of each 21-day cycle for up to 6 cycles. Cyclophosphamide: Cyclophosphamide 750 mg/m^2 intravenous (IV) on Day 5 of each cycle up to 6 cycles Doxorubicin: Doxorubicin 10 mg/m^2/day continuous intravenous infusion (CIVI) on Days 1-4 of each cycle up to 6 cycles 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 Prednisone: Prednisone 60 mg/m^2 by mouth (PO) twice a day (BID) Days 1-5 (total 120mg/m^2/day) |
| BG001 | Dose Escalation: Arm 1, Dose Level 1, Modified: 30mg Copanlisib | Copanlisib intravenous (IV) per dose level (30 mg) on day 1 of each 21-day cycle in combination with standard dosing dose adjusted rituximab, etoposide, prednisolone, vincristine, cyclophosphamide, doxorubicin (DA-EPOCH-R) to determine recommended phase 2 dose (RP2D) and maximum tolerated dose (MTD) of copanlisib. Up to 6 cycles total. Rituximab: Rituximab 375 mg/m^2 intravenous (IV) per protocol on Day 1 of each cycle up to 6 cycles Etoposide: Etoposide 50 mg/m^2/day continuous intravenous infusion (CIVI) on Days 1-4 of each cycle up to 6 cycles Copanlisib: Copanlisib intravenous (IV) is administered at a fixed dose (30 mg) on day 1 of each 21-day cycle for up to 6 cycles. Cyclophosphamide: Cyclophosphamide 750 mg/m^2 intravenous (IV) on Day 5 of each cycle up to 6 cycles Doxorubicin: Doxorubicin 10 mg/m^2/day continuous intravenous infusion (CIVI) on Days 1-4 of each cycle up to 6 cycles |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants | Participants |
| ||||||||||||||||||
| Age, Continuous | Median | Full Range | years |
| |||||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| ||||||||||||||||||
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||||
| Race (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||||
| Region of Enrollment | Number | participants |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Maximum Tolerated Dose (MTD) and Recommended Phase II Dose (RP2D) | MTD and RP2D is defined as the dose level at which no more than 1 of up to 6 participants experience dose limiting toxicity (DLT) during the DLT period, and the dose below that at which at least 2 (of ≤6) participants have DLT as a result of treatment. A DLT is any treatment-emergent, clinically relevant, and related severe (grade ≥ 3) toxicity that is possibly, probably, or definitely related to copanlisib. | Posted | Number | Mg | 21 days |
|
|
| |||||||||||||||||||||||||||
| Secondary | Overall Response Rate (ORR) | ORR is the best response recorded from the start of the treatment until disease progression/recurrence determined by Kaplan-Meier method and reported along with a 95% confidence interval. Response was assessed by the Revised Response Criteria for Malignant Lymphoma criteria, and the Lugano Classification Response Criteria for Non-Hodgkin Lymphoma (NHL). Complete response (CR) is complete disappearance of all detectable evidence of disease and disease-related symptoms. Partial response (PR) is a ≥50% decrease in the sum of the product of the diameters of up to 6 of the largest dominant nodes or nodal masses. Progressive disease (PD) is appearance of any new nodal lesion ≥1.6 cm in greatest tumor dimension or ≥1.1 cm in short axis during or after the end of therapy. A participant is considered to have stable disease (SD) when he or she fails to attain the criteria needed for a CR, PR, or Minimal Response (MR) but does not fulfill those for PD. | Posted | Number | 95% Confidence Interval | Percentage of participants | Response was assessed after cycles 1, 3 and 6 (each cycle is 21 days), approximately 63 days. |
| ||||||||||||||||||||||||||||
| Secondary | Progression-free Survival (PFS) | PFS is defined as the time from date of study enrollment until time of disease relapse, disease progression, or death, whichever occurs first, assessed every 3-6 months The progression free survival will be determined by the Kaplan-Meier method and reported along with a 95% confidence interval. Response was assessed by the Revised Response Criteria for Malignant Lymphoma criteria, and the Lugano Classification Response Criteria for Non-Hodgkin Lymphoma (NHL). Disease relapse is Progressive disease (PD) is appearance of any new nodal lesion ≥1.6 cm in greatest tumor dimension or ≥1.1 cm in short axis during or after the end of therapy or increase by ≥50% from PPD (cross product of the longest transverse diameter and perpendicular diameter) nadir. | Posted | Median | 95% Confidence Interval | Months | Time from enrollment to progression or death, approximately 9 months. |
| ||||||||||||||||||||||||||||
| Secondary | Complete Response Rate | Response was assessed by the Revised Response Criteria for Malignant Lymphoma criteria, and the Lugano Classification Response Criteria for Non-Hodgkin Lymphoma (NHL). Complete response (CR) is complete disappearance of all detectable evidence of disease and disease-related symptoms. The response rate will be determined by Kaplan-Meier method and reported along with a 95% confidence interval. | Posted | Number | 95% Confidence Interval | Percentage of participants | Response was assessed after cycles 1, 3 and 6 (each cycle is 21 days). Approximately 63 days. |
| ||||||||||||||||||||||||||||
| Secondary | Overall Survival (OS) | OS is defined as the time from the date of study enrollment until death from any cause, assessed every 3-6 months. OS will be determined by the Kaplan-Meier method and reported along with a 95% confidence interval. | Posted | Median | 95% Confidence Interval | Months | Time from enrollment to death, approximately 1 year |
| ||||||||||||||||||||||||||||
| Secondary | Event-free Survival (EFS) | EFS is defined as the time from the date of study enrollment until time of disease relapse from complete response (CR), disease progression, initiation of subsequent systemic anti-lymphoma therapy for either positron-emission tomography (PET)-positive or biopsy-proven residual disease, or death, whichever occurs first. The EFS will be determined by the Kaplan-Meier method and reported along with a 95% confidence interval. Response was assessed by the Revised Response Criteria for Malignant Lymphoma criteria, and the Lugano Classification Response Criteria for Non-Hodgkin Lymphoma (NHL). Complete response (CR) is complete disappearance of all detectable evidence of disease and disease-related symptoms. Progressive disease (PD) is appearance of any new nodal lesion ≥1.6 cm in greatest tumor dimension or ≥1.1 cm in short axis during or after the end of therapy. Disease relapse is Progressive disease (PD), an appearance of any new nodal lesion ≥1.6 cm in greatest tumor dimension. | Posted | Median | 95% Confidence Interval | Months | Time from enrollment to next line of anti-lymphoma therapy, progressive disease, or death. Approximately 6 months. |
| ||||||||||||||||||||||||||||
| Secondary | Number of Serious and/or Non-serious Grades 3-5 Adverse Events Related to Copanlisib | Rate and severity of adverse events (AEs) summarized by grade and type of toxicity. AE's were assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life-threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned. Grade 3 is severe. Grade 4 is life-threatening. Grade 5 is death related to adverse event. | Posted | Number | Adverse events | An average of 245.5 days |
| |||||||||||||||||||||||||||||
| Other Pre-specified | Number of Participants With Serious and/or Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0) | Here is the number of participants with serious and/or non-serious adverse events assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life-threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned. | Posted | Count of Participants | Participants | Date treatment consent signed to date off study, an average of 245.5 days |
| |||||||||||||||||||||||||||||
| Other Pre-specified | Number of Participants With Dose Limiting-toxicity (DLT) | A DLT is any treatment-emergent, clinically relevant, and related severe (grade ≥ 3) toxicity that is possibly, probably or definitely related to copanlisib. | Posted | Count of Participants | Participants | 21 days |
|
Date treatment consent signed to date off study, an average of 245.5 days.
Not provided
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Dose Escalation: Arm 1, Dose Level 1, Original: 30mg Copanlisib | Copanlisib intravenous (IV) per dose level (30 mg) on days 1 and 5 of each 21-day cycle in combination with standard dosing dose adjusted rituximab, etoposide, prednisolone, vincristine, cyclophosphamide, doxorubicin (DA-EPOCH-R) to determine recommended phase 2 dose (RP2D) and maximum tolerated dose (MTD) of copanlisib. Up to 6 cycles total. Rituximab: Rituximab 375 mg/m^2 intravenous (IV) per protocol on Day 1 of each cycle up to 6 cycles Etoposide: Etoposide 50 mg/m^2/day continuous intravenous infusion (CIVI) on Days 1-4 of each cycle up to 6 cycles Copanlisib: Copanlisib intravenous (IV) is administered at a fixed dose (30 mg) on days 1 and 5 of each 21-day cycle for up to 6 cycles. Cyclophosphamide: Cyclophosphamide 750 mg/m^2 intravenous (IV) on Day 5 of each cycle up to 6 cycles Doxorubicin: Doxorubicin 10 mg/m^2/day continuous intravenous infusion (CIVI) on Days 1-4 of each cycle up to 6 cycles 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 Prednisone: Prednisone 60 mg/m^2 by mouth (PO) twice a day (BID) Days 1-5 (total 120mg/m^2/day) | 5 | 5 | 2 | 5 | 5 | 5 |
| EG001 | Dose Escalation: Arm 1, Dose Level 1, Modified: 30mg Copanlisib | Copanlisib intravenous (IV) per dose level (30 mg) on day 1 of each 21-day cycle in combination with standard dosing dose adjusted rituximab, etoposide, prednisolone, vincristine, cyclophosphamide, doxorubicin (DA-EPOCH-R) to determine recommended phase 2 dose (RP2D) and maximum tolerated dose (MTD) of copanlisib. Up to 6 cycles total. Rituximab: Rituximab 375 mg/m^2 intravenous (IV) per protocol on Day 1 of each cycle up to 6 cycles Etoposide: Etoposide 50 mg/m^2/day continuous intravenous infusion (CIVI) on Days 1-4 of each cycle up to 6 cycles Copanlisib: Copanlisib intravenous (IV) is administered at a fixed dose (30 mg) on day 1 of each 21-day cycle for up to 6 cycles. Cyclophosphamide: Cyclophosphamide 750 mg/m^2 intravenous (IV) on Day 5 of each cycle up to 6 cycles Doxorubicin: Doxorubicin 10 mg/m^2/day continuous intravenous infusion (CIVI) on Days 1-4 of each cycle up to 6 cycles 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 Prednisone: Prednisone 60 mg/m^2 by mouth (PO) twice a day (BID) Days 1-5 (total 120mg/m^2/day) | 0 | 3 | 0 | 3 | 3 | 3 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Febrile neutropenia | Blood and lymphatic system disorders | CTCAE (5.0) | Systematic Assessment |
| |
| Generalized muscle weakness | Musculoskeletal and connective tissue disorders | CTCAE (5.0) | Systematic Assessment |
| |
| Multi-organ failure | General disorders | CTCAE (5.0) | Systematic Assessment |
| |
| Platelet count decreased | Investigations | CTCAE (5.0) | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anemia | Blood and lymphatic system disorders | CTCAE (5.0) | Systematic Assessment |
| |
| Anxiety | Psychiatric disorders | CTCAE (5.0) | Systematic Assessment |
| |
| Bacteremia | Infections and infestations | CTCAE (5.0) | Systematic Assessment |
| |
| Diarrhea | Gastrointestinal disorders | CTCAE (5.0) | Systematic Assessment |
| |
| Edema limbs | General disorders | CTCAE (5.0) | Systematic Assessment |
| |
| Fatigue | General disorders | CTCAE (5.0) | Systematic Assessment |
| |
| Febrile neutropenia | Blood and lymphatic system disorders | CTCAE (5.0) | Systematic Assessment |
| |
| Headache | Nervous system disorders | CTCAE (5.0) | Systematic Assessment |
| |
| Hyperglycemia | Metabolism and nutrition disorders | CTCAE (5.0) | Systematic Assessment |
| |
| Hypokalemia | Metabolism and nutrition disorders | CTCAE (5.0) | Systematic Assessment |
| |
| Insomnia | Psychiatric disorders | CTCAE (5.0) | Systematic Assessment |
| |
| Mucositis oral | Gastrointestinal disorders | CTCAE (5.0) | Systematic Assessment |
| |
| Neutrophil count decreased | Investigations | CTCAE (5.0) | Systematic Assessment |
| |
| Non-cardiac chest pain | Musculoskeletal and connective tissue disorders | CTCAE (5.0) | Systematic Assessment |
| |
| Platelet count decreased | Investigations | CTCAE (5.0) | Systematic Assessment |
| |
| Pleural effusion | Respiratory, thoracic and mediastinal disorders | CTCAE (5.0) | Systematic Assessment |
| |
| Rash maculo-papular | Skin and subcutaneous tissue disorders | CTCAE (5.0) | Systematic Assessment |
| |
| Rectal pain | Gastrointestinal disorders | CTCAE (5.0) | Systematic Assessment |
| |
| Respiratory failure | Respiratory, thoracic and mediastinal disorders | CTCAE (5.0) | Systematic Assessment |
| |
| Skin infection | Infections and infestations | CTCAE (5.0) | Systematic Assessment |
| |
| Vaginal inflammation | Reproductive system and breast disorders | CTCAE (5.0) | Systematic Assessment |
|
Not provided
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Mark Roschewski | National Cancer Institute | 240-760-6183 | mark.roschewski@nih.gov |
| May 16, 2024 |
| Prot_SAP_000.pdf |
| ICF | No | No | Yes | Informed Consent Form: Cohort Screening Affected Subject Consent | Mar 28, 2023 | Jun 13, 2024 | ICF_001.pdf |
| ICF | No | No | Yes | Informed Consent Form: Cohort Standard Affected Subject Consent | May 11, 2023 | Jun 13, 2024 | ICF_002.pdf |
| ID | Term |
|---|---|
| D002051 | Burkitt Lymphoma |
| D016403 | Lymphoma, Large B-Cell, Diffuse |
| ID | Term |
|---|---|
| D020031 | Epstein-Barr Virus Infections |
| D006566 | Herpesviridae Infections |
| D004266 | DNA Virus Infections |
| D014777 | Virus Diseases |
| D007239 | Infections |
| D014412 | Tumor Virus Infections |
| D016393 | Lymphoma, B-Cell |
| D008228 | Lymphoma, Non-Hodgkin |
| D008223 | Lymphoma |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D008232 | Lymphoproliferative Disorders |
| D008206 | Lymphatic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D007160 | Immunoproliferative Disorders |
| D007154 | Immune System Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| D000069283 | Rituximab |
| D005047 | Etoposide |
| C061400 | etoposide phosphate |
| C000589253 | copanlisib |
| D003520 | Cyclophosphamide |
| D004317 | Doxorubicin |
| D014750 | Vincristine |
| D011241 | Prednisone |
| D004452 | Echocardiography |
| D004562 | Electrocardiography |
| D014057 | Tomography, X-Ray Computed |
| D013129 | Spinal Puncture |
| ID | Term |
|---|---|
| D058846 | Antibodies, Monoclonal, Murine-Derived |
| D000911 | Antibodies, Monoclonal |
| D000906 | Antibodies |
| D007136 | Immunoglobulins |
| D007162 | Immunoproteins |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D012712 | Serum Globulins |
| D005916 | Globulins |
| D011034 | Podophyllotoxin |
| D013764 | Tetrahydronaphthalenes |
| D009281 | Naphthalenes |
| D011084 | Polycyclic Aromatic Hydrocarbons |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D011083 | Polycyclic Compounds |
| D005960 | Glucosides |
| D006027 | Glycosides |
| D002241 | Carbohydrates |
| D010752 | Phosphoramide Mustards |
| D009588 | Nitrogen Mustard Compounds |
| D009150 | Mustard Compounds |
| D006846 | Hydrocarbons, Halogenated |
| D063088 | Phosphoramides |
| D009943 | Organophosphorus Compounds |
| D003630 | Daunorubicin |
| D018943 | Anthracyclines |
| D009279 | Naphthacenes |
| D000617 | Aminoglycosides |
| D014748 | Vinca Alkaloids |
| D046948 | Secologanin Tryptamine Alkaloids |
| D026121 | Indole Alkaloids |
| D000470 | Alkaloids |
| D006571 | Heterocyclic Compounds |
| D007211 | Indoles |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D054836 | Indolizidines |
| D007212 | Indolizines |
| D011244 | Pregnadienediols |
| D011245 | Pregnadienes |
| D011278 | Pregnanes |
| D013256 | Steroids |
| D000072473 | Fused-Ring Compounds |
| D057791 | Cardiac Imaging Techniques |
| D003952 | Diagnostic Imaging |
| D019937 | Diagnostic Techniques and Procedures |
| D003933 | Diagnosis |
| D014463 | Ultrasonography |
| D006334 | Heart Function Tests |
| D003935 | Diagnostic Techniques, Cardiovascular |
| D004568 | Electrodiagnosis |
| D007090 | Image Interpretation, Computer-Assisted |
| D011856 | Radiographic Image Enhancement |
| D007089 | Image Enhancement |
| D010781 | Photography |
| D011859 | Radiography |
| D014056 | Tomography, X-Ray |
| D014054 | Tomography |
| D001706 | Biopsy |
| D013048 | Specimen Handling |
| D019411 | Clinical Laboratory Techniques |
| D003943 | Diagnostic Techniques, Neurological |
| D011677 | Punctures |
| D013812 | Therapeutics |
| D013514 | Surgical Procedures, Operative |
| D008919 | Investigative Techniques |
Not provided
Not provided
| >=65 years |
|
| Male |
|
| Not Hispanic or Latino |
|
| Unknown or Not Reported |
|
| Asian |
|
| Native Hawaiian or Other Pacific Islander |
|
| Black or African American |
|
| White |
|
| More than one race |
|
| Unknown or Not Reported |
|
| OG001 | Dose Escalation: Arm 1, Dose Level 1, Modified: 30mg Copanlisib | Copanlisib intravenous (IV) per dose level (30 mg) on day 1 of each 21-day cycle in combination with standard dosing dose adjusted rituximab, etoposide, prednisolone, vincristine, cyclophosphamide, doxorubicin (DA-EPOCH-R) to determine recommended phase 2 dose (RP2D) and maximum tolerated dose (MTD) of copanlisib. Up to 6 cycles total. Rituximab: Rituximab 375 mg/m^2 intravenous (IV) per protocol on Day 1 of each cycle up to 6 cycles Etoposide: Etoposide 50 mg/m^2/day continuous intravenous infusion (CIVI) on Days 1-4 of each cycle up to 6 cycles Copanlisib: Copanlisib intravenous (IV) is administered at a fixed dose (30 mg) on day 1 of each 21-day cycle for up to 6 cycles. Cyclophosphamide: Cyclophosphamide 750 mg/m^2 intravenous (IV) on Day 5 of each cycle up to 6 cycles Doxorubicin: Doxorubicin 10 mg/m^2/day continuous intravenous infusion (CIVI) on Days 1-4 of each cycle up to 6 cycles 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 Prednisone: Prednisone 60 mg/m^2 by mouth (PO) twice a day (BID) Days 1-5 (total 120mg/m^2/day) |
|
|
| OG001 | Dose Escalation: Arm 1, Dose Level 1, Modified: 30mg Copanlisib | Copanlisib intravenous (IV) per dose level (30 mg) on day 1 of each 21-day cycle in combination with standard dosing dose adjusted rituximab, etoposide, prednisolone, vincristine, cyclophosphamide, doxorubicin (DA-EPOCH-R) to determine recommended phase 2 dose (RP2D) and maximum tolerated dose (MTD) of copanlisib. Up to 6 cycles total. Rituximab: Rituximab 375 mg/m^2 intravenous (IV) per protocol on Day 1 of each cycle up to 6 cycles Etoposide: Etoposide 50 mg/m^2/day continuous intravenous infusion (CIVI) on Days 1-4 of each cycle up to 6 cycles Copanlisib: Copanlisib intravenous (IV) is administered at a fixed dose (30 mg) on day 1 of each 21-day cycle for up to 6 cycles. Cyclophosphamide: Cyclophosphamide 750 mg/m^2 intravenous (IV) on Day 5 of each cycle up to 6 cycles Doxorubicin: Doxorubicin 10 mg/m^2/day continuous intravenous infusion (CIVI) on Days 1-4 of each cycle up to 6 cycles 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 Prednisone: Prednisone 60 mg/m^2 by mouth (PO) twice a day (BID) Days 1-5 (total 120mg/m^2/day) |
|
|
| OG001 | Dose Escalation: Arm 1, Dose Level 1, Modified: 30mg Copanlisib | Copanlisib intravenous (IV) per dose level (30 mg) on day 1 of each 21-day cycle in combination with standard dosing dose adjusted rituximab, etoposide, prednisolone, vincristine, cyclophosphamide, doxorubicin (DA-EPOCH-R) to determine recommended phase 2 dose (RP2D) and maximum tolerated dose (MTD) of copanlisib. Up to 6 cycles total. Rituximab: Rituximab 375 mg/m^2 intravenous (IV) per protocol on Day 1 of each cycle up to 6 cycles Etoposide: Etoposide 50 mg/m^2/day continuous intravenous infusion (CIVI) on Days 1-4 of each cycle up to 6 cycles Copanlisib: Copanlisib intravenous (IV) is administered at a fixed dose (30 mg) on day 1 of each 21-day cycle for up to 6 cycles. Cyclophosphamide: Cyclophosphamide 750 mg/m^2 intravenous (IV) on Day 5 of each cycle up to 6 cycles Doxorubicin: Doxorubicin 10 mg/m^2/day continuous intravenous infusion (CIVI) on Days 1-4 of each cycle up to 6 cycles 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 Prednisone: Prednisone 60 mg/m^2 by mouth (PO) twice a day (BID) Days 1-5 (total 120mg/m^2/day) |
|
|
Copanlisib intravenous (IV) per dose level (30 mg) on day 1 of each 21-day cycle in combination with standard dosing dose adjusted rituximab, etoposide, prednisolone, vincristine, cyclophosphamide, doxorubicin (DA-EPOCH-R) to determine recommended phase 2 dose (RP2D) and maximum tolerated dose (MTD) of copanlisib. Up to 6 cycles total. Rituximab: Rituximab 375 mg/m^2 intravenous (IV) per protocol on Day 1 of each cycle up to 6 cycles Etoposide: Etoposide 50 mg/m^2/day continuous intravenous infusion (CIVI) on Days 1-4 of each cycle up to 6 cycles Copanlisib: Copanlisib intravenous (IV) is administered at a fixed dose (30 mg) on day 1 of each 21-day cycle for up to 6 cycles. Cyclophosphamide: Cyclophosphamide 750 mg/m^2 intravenous (IV) on Day 5 of each cycle up to 6 cycles Doxorubicin: Doxorubicin 10 mg/m^2/day continuous intravenous infusion (CIVI) on Days 1-4 of each cycle up to 6 cycles 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 Prednisone: Prednisone 60 mg/m^2 by mouth (PO) twice a day (BID) Days 1-5 (total 120mg/m^2/day) |
|
|
| OG001 | Dose Escalation: Arm 1, Dose Level 1, Modified: 30mg Copanlisib | Copanlisib intravenous (IV) per dose level (30 mg) on day 1 of each 21-day cycle in combination with standard dosing dose adjusted rituximab, etoposide, prednisolone, vincristine, cyclophosphamide, doxorubicin (DA-EPOCH-R) to determine recommended phase 2 dose (RP2D) and maximum tolerated dose (MTD) of copanlisib. Up to 6 cycles total. Rituximab: Rituximab 375 mg/m^2 intravenous (IV) per protocol on Day 1 of each cycle up to 6 cycles Etoposide: Etoposide 50 mg/m^2/day continuous intravenous infusion (CIVI) on Days 1-4 of each cycle up to 6 cycles Copanlisib: Copanlisib intravenous (IV) is administered at a fixed dose (30 mg) on day 1 of each 21-day cycle for up to 6 cycles. Cyclophosphamide: Cyclophosphamide 750 mg/m^2 intravenous (IV) on Day 5 of each cycle up to 6 cycles Doxorubicin: Doxorubicin 10 mg/m^2/day continuous intravenous infusion (CIVI) on Days 1-4 of each cycle up to 6 cycles 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 Prednisone: Prednisone 60 mg/m^2 by mouth (PO) twice a day (BID) Days 1-5 (total 120mg/m^2/day) |
|
|
| OG001 | Dose Escalation: Arm 1, Dose Level 1, Modified: 30mg Copanlisib | Copanlisib intravenous (IV) per dose level (30 mg) on day 1 of each 21-day cycle in combination with standard dosing dose adjusted rituximab, etoposide, prednisolone, vincristine, cyclophosphamide, doxorubicin (DA-EPOCH-R) to determine recommended phase 2 dose (RP2D) and maximum tolerated dose (MTD) of copanlisib. Up to 6 cycles total. Rituximab: Rituximab 375 mg/m^2 intravenous (IV) per protocol on Day 1 of each cycle up to 6 cycles Etoposide: Etoposide 50 mg/m^2/day continuous intravenous infusion (CIVI) on Days 1-4 of each cycle up to 6 cycles Copanlisib: Copanlisib intravenous (IV) is administered at a fixed dose (30 mg) on day of each 21-day cycle for up to 6 cycles. Cyclophosphamide: Cyclophosphamide 750 mg/m^2 intravenous (IV) on Day 5 of each cycle up to 6 cycles Doxorubicin: Doxorubicin 10 mg/m^2/day continuous intravenous infusion (CIVI) on Days 1-4 of each cycle up to 6 cycles 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 Prednisone: Prednisone 60 mg/m^2 by mouth (PO) twice a day (BID) Days 1-5 (total 120mg/m^2/day) |
|
|
| OG001 | Dose Escalation: Arm 1, Dose Level 1, Modified: 30mg Copanlisib | Copanlisib intravenous (IV) per dose level (30 mg) on day 1 of each 21-day cycle in combination with standard dosing dose adjusted rituximab, etoposide, prednisolone, vincristine, cyclophosphamide, doxorubicin (DA-EPOCH-R) to determine recommended phase 2 dose (RP2D) and maximum tolerated dose (MTD) of copanlisib. Up to 6 cycles total. Rituximab: Rituximab 375 mg/m^2 intravenous (IV) per protocol on Day 1 of each cycle up to 6 cycles Etoposide: Etoposide 50 mg/m^2/day continuous intravenous infusion (CIVI) on Days 1-4 of each cycle up to 6 cycles Copanlisib: Copanlisib intravenous (IV) is administered at a fixed dose (30 mg) on day 1 of each 21-day cycle for up to 6 cycles. Cyclophosphamide: Cyclophosphamide 750 mg/m^2 intravenous (IV) on Day 5 of each cycle up to 6 cycles Doxorubicin: Doxorubicin 10 mg/m^2/day continuous intravenous infusion (CIVI) on Days 1-4 of each cycle up to 6 cycles 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 Prednisone: Prednisone 60 mg/m^2 by mouth (PO) twice a day (BID) Days 1-5 (total 120mg/m^2/day) |
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Copanlisib intravenous (IV) per dose level (30 mg) on day 1 of each 21-day cycle in combination with standard dosing dose adjusted rituximab, etoposide, prednisolone, vincristine, cyclophosphamide, doxorubicin (DA-EPOCH-R) to determine recommended phase 2 dose (RP2D) and maximum tolerated dose (MTD) of copanlisib. Up to 6 cycles total. Rituximab: Rituximab 375 mg/m^2 intravenous (IV) per protocol on Day 1 of each cycle up to 6 cycles Etoposide: Etoposide 50 mg/m^2/day continuous intravenous infusion (CIVI) on Days 1-4 of each cycle up to 6 cycles Copanlisib: Copanlisib intravenous (IV) is administered at a fixed dose (30 mg) on day 1 of each 21-day cycle for up to 6 cycles. Cyclophosphamide: Cyclophosphamide 750 mg/m^2 intravenous (IV) on Day 5 of each cycle up to 6 cycles Doxorubicin: Doxorubicin 10 mg/m^2/day continuous intravenous infusion (CIVI) on Days 1-4 of each cycle up to 6 cycles 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 Prednisone: Prednisone 60 mg/m^2 by mouth (PO) twice a day (BID) Days 1-5 (total 120mg/m^2/day) |
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