Study Stopped
The study was terminated early because copanlisib was removed from the market by the Food and Drug Administration (FDA) and the manufacturer.
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
2 other identifiers
interventional
8
1 country
1
Brief 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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for phase_1
Started Mar 2022
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
June 18, 2021
CompletedFirst Posted
Study publicly available on registry
June 22, 2021
CompletedStudy Start
First participant enrolled
March 24, 2022
CompletedPrimary Completion
Last participant's last visit for primary outcome
November 30, 2023
CompletedStudy Completion
Last participant's last visit for all outcomes
November 30, 2023
CompletedResults Posted
Study results publicly available
July 9, 2024
CompletedJuly 9, 2024
June 1, 2024
1.7 years
June 18, 2021
May 16, 2024
June 13, 2024
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
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
Secondary Outcomes (6)
Overall Response Rate (ORR)
Response was assessed after cycles 1, 3 and 6 (each cycle is 21 days), approximately 63 days.
Progression-free Survival (PFS)
Time from enrollment to progression or death, approximately 9 months.
Complete Response Rate
Response was assessed after cycles 1, 3 and 6 (each cycle is 21 days). Approximately 63 days.
Overall Survival (OS)
Time from enrollment to death, approximately 1 year
Event-free Survival (EFS)
Time from enrollment to next line of anti-lymphoma therapy, progressive disease, or death. Approximately 6 months.
- +1 more secondary outcomes
Other Outcomes (2)
Number of Participants With Serious and/or Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0)
Date treatment consent signed to date off study, an average of 245.5 days
Number of Participants With Dose Limiting-toxicity (DLT)
21 days
Study Arms (2)
Arm 1- Dose Escalation, Original Copanlisib Intravenous (IV)
EXPERIMENTALCopanlisib 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)
EXPERIMENTALCopanlisib 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.
Interventions
Rituximab 375 mg/m\^2 intravenous (IV) per protocol on Day 1 of each cycle up to 6 cycles
Etoposide 50 mg/m\^2/day continuous intravenous infusion (CIVI) on Days 1-4 of each cycle up to 6 cycles
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
Cyclophosphamide 750 mg/m\^2 intravenous (IV) on Day 5 of each cycle up to 6 cycles
Doxorubicin 10 mg/m\^2/day continuous intravenous infusion (CIVI) on Days 1-4 of each cycle up to 6 cycles
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 60 mg/m\^2 by mouth (PO) twice a day (BID) Days 1-5 (total 120mg/m\^2/day)
At screening.
At screening.
At screening.
At screening, baseline, after cycle 1, 3, and 6, and end of treatment.
At screening, baseline, after cycle 1, 3, and 6, end of treatment and follow-up.
At screening and end of treatment.
At screening and end of treatment.
Baseline and end of treatment.
Eligibility Criteria
You may qualify if:
- 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:
- Burkitt lymphoma
- Burkitt-like lymphoma with 11q aberration
- High-grade B-cell lymphoma, nor otherwise specified (NOS)
- High-grade B-cell lymphoma, with myelocytomatosis (MYC) and B-cell lymphoma 2 (BCL2) and/or B-cell lymphoma 6 (BCL6) rearrangements
- 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
- +14 more criteria
You may not qualify if:
- 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)
- +10 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892, United States
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Dr. Mark Roschewski
- Organization
- National Cancer Institute
Study Officials
- PRINCIPAL INVESTIGATOR
Mark J Roschewski, M.D.
National Cancer Institute (NCI)
Publication Agreements
- PI is Sponsor Employee
- No
- Restrictive Agreement
- No
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SEQUENTIAL
- Sponsor Type
- NIH
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Investigator
Study Record Dates
First Submitted
June 18, 2021
First Posted
June 22, 2021
Study Start
March 24, 2022
Primary Completion
November 30, 2023
Study Completion
November 30, 2023
Last Updated
July 9, 2024
Results First Posted
July 9, 2024
Record last verified: 2024-06
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP, ICF
- Time Frame
- 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.
- Access Criteria
- 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.
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).