Ibrutinib, Rituximab, Etoposide, Prednisone, Vincristine Sulfate, Cyclophosphamide, and Doxorubicin Hydrochloride in Treating Patients With HIV-Positive Stage II-IV Diffuse Large B-Cell Lymphomas
A Pilot Study of Ibrutinib and R-da-EPOCH for Front Line Treatment of AIDS-Related Lymphomas
3 other identifiers
interventional
46
1 country
19
Brief Summary
This phase I trial studies the side effect and best dose of ibrutinib in combination with rituximab, etoposide, prednisone, vincristine sulfate, cyclophosphamide, and doxorubicin hydrochloride in treating patients with human immunodeficiency virus (HIV)-positive stage II-IV diffuse large B-cell lymphomas. Ibrutinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies, such as rituximab, may interfere with the ability of cancer cells to grow and spread. Drugs used in chemotherapy, such as etoposide, prednisone, vincristine sulfate, cyclophosphamide, and doxorubicin hydrochloride, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving ibrutinib and etoposide, prednisone, vincristine sulfate, cyclophosphamide, and doxorubicin hydrochloride may work better in treating patients with HIV-positive diffuse large B-cell lymphomas.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_1
Started Mar 2018
Longer than P75 for phase_1
19 active sites
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
July 17, 2017
CompletedFirst Posted
Study publicly available on registry
July 18, 2017
CompletedStudy Start
First participant enrolled
March 16, 2018
CompletedPrimary Completion
Last participant's last visit for primary outcome
October 10, 2024
CompletedResults Posted
Study results publicly available
April 2, 2026
CompletedStudy Completion
Last participant's last visit for all outcomes
July 16, 2026
ExpectedApril 13, 2026
January 1, 2026
6.6 years
July 17, 2017
November 20, 2025
April 9, 2026
Conditions
Outcome Measures
Primary Outcomes (2)
Maximum Tolerated Dose (MTD) of Ibrutinib in Combination With Chemotherapy
Will be descriptive and will be reported in tabular format with the appropriate summary statistics (count and percentage). In the dose-finding portion, the number of dose limiting toxicities (DLTs) identified among the DLT-evaluable subjects will be listed and summarized by dose level. The safety variables will be listed and summarized for (1) subjects in the dose-finding portion, (2) subjects in the dose expansion cohort (DEC), and (3) all subjects in the study.
Up to 21 days
Recommended Phase II Dose (RP2D) of Ibrutinib in Combination With Chemotherapy
Will be descriptive and will be reported in tabular format with the appropriate summary statistics (count and percentage). In the dose-finding portion, the number of DLTs identified among the DLT-evaluable subjects will be listed and summarized by dose level. The safety variables will be listed and summarized for (1) subjects in the dose-finding portion, (2) subjects in the DEC, and (3) all subjects in the study.
Up to 21 days
Secondary Outcomes (17)
Incidence of Adverse Events Graded Using Common Terminology Criteria for Adverse Events Version 4.0
Up to 5 years
Complete Response Rates
Up to 5 years
Progression Free Survival (PFS)
1 year
Progression Free Survival (PFS)
2 years
Overall Survival (OS)
1 year
- +12 more secondary outcomes
Study Arms (1)
Treatment (R-da-EPOCH)
EXPERIMENTALPatients receive rituximab IV on day 1 (for CD20 positive patients only), etoposide IV over 96 hours on days 1-4, doxorubicin hydrochloride IV over 96 hours on days 1-4, vincristine sulfate IV over 96 hours on days 1-4, prednisone PO daily on days 1-5, cyclophosphamide IV over 1 hour on day 5, and ibrutinib PO QD on days 1-21. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients also receive pegfilgrastim SC from 1 calendar day up to 48 hours or filgrastim SC beginning on day 6 for up to 10 days until ANC is satisfactory.
Interventions
Given IV
Given SC
Given PO
Given IV
Given IV
Given IV
Given SC
Given PO
Given IV
Eligibility Criteria
You may qualify if:
- Participants must have histologically (via at least a core or ideally, incisional or excisional biopsy) documented CD20 positive or negative diffuse large B-cell lymphoma (DLBCL)
- Tissue available from the diagnostic biopsy in the form of blocks, tissue cores, or slides available for submission to central pathology is required for all participants enrolled to this study, for analysis of integral biomarkers. Formalin-fixed paraffin-embedded tissue from diagnostic tissue is acceptable and recommended; submission of the institutional diagnostic slides is also preferred for all participants enrolled in the study. Tissue and diagnostic slides are required to be submitted within 1 month of enrollment
- Stage II-IV disease; participant will need measurable disease by computed tomography (CT) or positron emission tomography (PET) scans if enrolled in the dose-expansion cohort
- HIV positive; documentation of HIV-1 infection by means of any one of the following:
- Documentation of HIV diagnosis in the medical record by a licensed health care provider;
- Documentation of receipt of ART (at least three different medications) by a licensed health care provider (documentation may be a record of an antiretroviral therapy (ART) prescription in the participant's medical record, a written prescription in the name of the participant for ART, or pill bottles for ART with a label showing the participant's name);
- HIV-1 ribonucleic acid (RNA) detection by a licensed HIV-1 RNA assay demonstrating \> 1000 RNA copies/mL;
- Any licensed HIV screening antibody and/or HIV antibody/antigen combination assay confirmed by a second licensed HIV assay such as a HIV-1 western blot confirmation or HIV rapid multispot antibody differentiation assay
- NOTE: a "licensed" assay refers to a United States (U.S.) Food and Drug Administration (FDA)-approved assay, which is required for all investigational food drug (IND) studies
- For the dose-finding cohort participants lymphoma must be untreated. For the dose-expansion cohort participants may have either untreated lymphoma or may have received prior therapy
- Ages 18 - 64
- Eastern Cooperative Oncology Group (ECOG) performance status =\< 2 (Karnofsky \>= 50%)
- For the dose-finding cohort participants must have a CD4 count ≥ 100 cells/mm\^3. For the dose-expansion cohort participants may have any CD4 count, including a CD4 count \< 100 cells/mm\^3
- Absolute neutrophil count: \>= 1,000/mm\^3, unless decreased due to bone marrow involvement with lymphoma
- Platelets: \>= 75,000/mm\^3, unless decreased due to bone marrow involvement with lymphoma
- +10 more criteria
You may not qualify if:
- Participants who have had chemotherapy other than R-EPOCH, R-CHOP, or limited therapy, or radiotherapy other than palliative radiation for medical emergencies (like cord compression), within the last 4 weeks
- A maximum of one cycle of combination chemotherapy, including rituximab-containing regimens R-CHOP and R-EPOCH. The start of previous chemotherapy cycle must occur at least 21 days but no more than 28 days prior to beginning treatment under this protocol, and such cycle will count towards the maximum of 6 cycles under this study (i.e., cycle off study will count as cycle 1) OR
- prior cycle of limited therapy including cyclophosphamide and/or rituximab and/or glucocorticoids to improve hepatic or renal function impaired due to lymphoma involvement. The start of this therapy may occur up to 28 days prior to beginning treatment under this protocol; cyclophosphamide administration must have been completed at least 14 days prior to initiation of protocol therapy. Such treatment will not count towards the maximum of 6 cycles under this study (i.e., participants will receive 6 cycles on study)
- Participants who are receiving any other investigational agents
- Participants who have previously received ibrutinib for another indication
- Expected survival \< 2 months
- Participants with a history of an opportunistic fungal infection or active fungal infection requiring, or at high risk of requiring, prophylactic or treatment with fluconazole, voriconazole or posaconazole
- Participants with known brain metastases from solid tumors should be excluded from this clinical trial
- Presence of second active tumor, other than non-melanoma skin cancer, carcinoma in situ of the cervix, or Kaposi's sarcoma (KS) that requires systemic therapy
- For the dose-finding cohort, participants with known or suspected parenchymal brain, spinal cord, leptomeningeal disease prior to study enrollment will be excluded. For the dose-expansion cohort participants with known or suspected parenchymal brain or spinal cord disease, or symptomatic leptomeningeal disease will be excluded. Asymptomatic leptomeningeal disease will be allowed
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to ibrutinib or other agents used in study
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that, in the opinions of the investigator, would limit compliance with study requirements
- Pregnancy or breastfeeding; a pregnancy test must be performed within 7 days prior to ibrutinib initiation in women of childbearing potential; pregnant women; breastfeeding must be discontinued because of unknown but potential risks in the nursing infant
- Unable to comply with the requirements of the protocol, or unable to provide adequate informed consent in the opinion of the principal investigator
- Serious, ongoing, non-malignant disease or infection, which in the opinion of the investigator and/or the sponsor would compromise other protocol objectives; participants with active opportunistic infections are ineligible
- +1 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (19)
UC San Diego Moores Cancer Center
La Jolla, California, 92093, United States
UCSF Medical Center-Parnassus
San Francisco, California, 94143, United States
University of Miami Miller School of Medicine-Sylvester Cancer Center
Miami, Florida, 33136, United States
Memorial Hospital West
Pembroke Pines, Florida, 33028, United States
John H Stroger Jr Hospital of Cook County
Chicago, Illinois, 60612, United States
University of Illinois College of Medicine - Chicago
Chicago, Illinois, 60612, United States
Johns Hopkins University/Sidney Kimmel Cancer Center
Baltimore, Maryland, 21287, United States
Boston Medical Center
Boston, Massachusetts, 02118, United States
Siteman Cancer Center at Washington University
St Louis, Missouri, 63110, United States
Washington University School of Medicine
St Louis, Missouri, 63110, United States
Mount Sinai Hospital
New York, New York, 10029, United States
Memorial Sloan Kettering Cancer Center
New York, New York, 10065, United States
Montefiore Medical Center - Moses Campus
The Bronx, New York, 10467, United States
Memorial Sloan Kettering Nassau
Uniondale, New York, 11553, United States
UNC Lineberger Comprehensive Cancer Center
Chapel Hill, North Carolina, 27599, United States
Ohio State University Comprehensive Cancer Center
Columbus, Ohio, 43210, United States
Pennsylvania Hospital
Philadelphia, Pennsylvania, 19107, United States
Fox Chase Cancer Center
Philadelphia, Pennsylvania, 19111, United States
Virginia Mason Medical Center
Seattle, Washington, 98101, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Deukwoo Kwon
- Organization
- Statistical and Data Analysis Center, AIDS Malignancy Consortium
Study Officials
- PRINCIPAL INVESTIGATOR
Ida C Wong-Sefidan
AIDS Malignancy Consortium
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- LTE60
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- NIH
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
July 17, 2017
First Posted
July 18, 2017
Study Start
March 16, 2018
Primary Completion
October 10, 2024
Study Completion (Estimated)
July 16, 2026
Last Updated
April 13, 2026
Results First Posted
April 2, 2026
Record last verified: 2026-01