AIDS-Related LymphomaPhase 1NCT03220022
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 Phase 1 study testing Cyclophosphamide, Doxorubicin Hydrochloride and Etoposide in people with AIDS-Related Lymphoma and Ann Arbor Stage II Diffuse Large B-Cell Lymphoma, run by National Cancer Institute (NCI) at 19 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 64 years
- Conditions the study is for
- AIDS-Related Lymphoma, Ann Arbor Stage II Diffuse Large B-Cell Lymphoma, Ann Arbor Stage III Diffuse Large B-Cell Lymphoma
- What is being tested?
- Cyclophosphamide, Doxorubicin Hydrochloride and Etoposide
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 46 participants
- Where
- 19 sitesUnited States
- Study dates
- 16 Mar 2018to 16 Jul 2027
- Phase
- Phase 1
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 64 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- 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);
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- 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
- Total bilirubin: =< 1.5 times the institutional upper limit of normal (ULN); if potentially due to lymphoma, in the dose-expansion cohort, the first cycle may be given without ibrutinib and if transaminitis and bilirubinemia improves to meet parameters, participant may be enrolled
- Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]): < 2 times the institutional ULN; if potentially due to lymphoma, in the dose-expansion cohort, the first cycle will be given without ibrutinib and if transaminitis and bilirubinemia improves to meet parameters, participant may be enrolled
- Creatinine levels below the normal institutional upper limits; or, creatinine clearance >= 50 mL/min/1.73 m^2 for participants with creatinine levels above institutional normal; unless decreased due to renal involvement by lymphoma
- Participants must not be on medications, including antiretroviral (ARV) regimens such as cobicistat, indinavir, or ritonavir, or agents with moderate or strong CYP3A4 inhibition; if on a moderate or strong CYP3A4 inhibitor regimen prior to study enrollment, participants must be switched to a qualifying regimen with the last dose of the strong CYP3A4 inhibitor taken at least one week before administration of ibrutinib
- Willingness of sexually active participants to use adequate contraception; both men and women of child-bearing potential treated or enrolled on this study must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) before study entry, for the duration of study participation, 90 days after completion of ibrutinib, and 12 months after the last dose of rituximab, whichever comes last; men who only have sex with other men do not need to use contraception specifically for this study (should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately)
- All participants will be required to be screened for hepatitis B; all participants who present with acute hepatitis B or show normal transaminases and are hepatitis B surface antigen (HBsAg) positive (+) and IgM+ for hepatitis core antigen will not be eligible for trial enrollment; per Infectious Diseases Society of America (IDSA) and Assistance for AIDS Specific Drugs (AASD) guidelines, those participants that show no immunity, defined by the lack of hepatitis B surface antibody, and show evidence of chronic infection (i.e. hepatitis B [HB]sAg+, HBcore+, hepatitis B surface antibody [HBsAB] negative [-]) will be required to be on anti-hepatitis B therapy, during the study, in order to be eligible; the exact hepatitis B therapy will be at the discretion of the infection disease specialist or investigator; if infected with hepatitis B, participants will be permitted to enroll in the study provided liver function tests meet criteria listed above, there is no evidence of cirrhosis AND participants will be required to be on anti-hepatitis B therapy
- All participants will be required to be screened for hepatitis C; if hepatitis C antibody positive, with or without a positive hepatitis C RNA level, participants will be permitted to enroll in the study provided liver function tests meet criteria listed, and have no evidence of cirrhosis; participants diagnosed with hepatitis C less than 6 months from trial enrollment will be considered to have acute hepatitis C, and will be excluded from study UNLESS hepatitis C viral load is undetectable
- Adequate cardiac function defined as an ejection fraction on echocardiogram (ECHO) or multi-gated acquisition (MUGA) that is at or above the institutional normal limits. For the dose-expansion cohort, if the participant had a pre-treatment ECHO prior to pre-study therapy which reports adequate cardiac function defined as an ejection fraction on ECHO or MUGA that is at or above the institutional normal limits, a repeat ECHO will not need to be repeated prior to start of study treatment
- Participants must be able to swallow oral pills
- Ability to understand and willing to sign a written informed consent document
Who cannot join
- 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
- For the dose-finding cohort prior cytotoxic chemotherapy or radiotherapy for this lymphoma is exclusionary. For the dose-expansion cohort participants may have received:
- 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
- 1 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)
- For the dose-finding cohort rituximab within 12 months prior to study registration will be exclusionary; only exception will be if rituximab was given for indications other than the treatment of aggressive lymphoma. For the dose-expansion cohort one cycle of rituximab as part of R-CHOP or R-EPOCH or limited therapy may be administered off study prior to enrollment; prior rituximab will also be allowed if rituximab was given for indications other than the treatment of aggressive lymphoma
- Participants who are receiving any other investigational agents
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- 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
- Major surgery, other than diagnostic surgery, occurring 4 weeks prior to study entry; splenectomy will not be considered an exclusionary major surgery
- History of cutaneous or mucocutaneous reactions, or diseases in the past, due to any cause, severe enough to cause hospitalization or an inability to eat or drink for > 2 days; this exclusion relates to the long-term possibility of severe cutaneous or mucocutaneous reactions to rituximab that might occur at increased frequency in participants who have had severe skin disease or reactions in the past
- Myocardial infarction (MI) within 6 months prior to study entry, New York Heart Association (NYHA) class II or greater heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, clinically significant pericardial disease, or electrocardiographic evidence of acute ischemic or active conduction system abnormalities
Trial locations and contacts
19 sites in 1 country.
19 sites in 1 country
United States19 sites
Johns Hopkins University/Sidney Kimmel Cancer Center
Baltimore, Maryland, 21287
Boston Medical Center
Boston, Massachusetts, 02118
UNC Lineberger Comprehensive Cancer Center
Chapel Hill, North Carolina, 27599
John H Stroger Jr Hospital of Cook County
Chicago, Illinois, 60612
University of Illinois College of Medicine - Chicago
Chicago, Illinois, 60612
Ohio State University Comprehensive Cancer Center
Columbus, Ohio, 43210
UC San Diego Moores Cancer Center
La Jolla, California, 92093
University of Miami Miller School of Medicine-Sylvester Cancer Center
Miami, Florida, 33136
Mount Sinai Hospital
New York, New York, 10029
Memorial Sloan Kettering Cancer Center
New York, New York, 10065
Memorial Hospital West
Pembroke Pines, Florida, 33028
Pennsylvania Hospital
Philadelphia, Pennsylvania, 19107
Fox Chase Cancer Center
Philadelphia, Pennsylvania, 19111
UCSF Medical Center-Parnassus
San Francisco, California, 94143
Virginia Mason Medical Center
Seattle, Washington, 98101
Siteman Cancer Center at Washington University
St Louis, Missouri, 63110
Washington University School of Medicine
St Louis, Missouri, 63110
Montefiore Medical Center - Moses Campus
The Bronx, New York, 10467
Memorial Sloan Kettering Nassau
Uniondale, New York, 11553
About this study
Official title: A Pilot Study of Ibrutinib and R-da-EPOCH for Front Line Treatment of AIDS-Related Lymphomas
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.
Read the detailed description
PRIMARY OBJECTIVES:
- To assess the safety and tolerability of ibrutinib and rituximab (R)-dose adjusted (da)-etoposide, prednisone, vincristine sulfate, cyclophosphamide, and doxorubicin hydrochloride (EPOCH) in participants with acquired immunodeficiency syndrome (AIDS)-related lymphomas (ARL).
SECONDARY OBJECTIVES:
- To evaluate the complete response (CR) rates of ARL to ibrutinib and R-da-EPOCH.
II. To measure the 1-year and 2-year overall and progression-free survival of participants with ARL treated with combination ibrutinib and R-da-EPOCH, including preliminary comparison of non-germinal center B-cell (GCB) with historical controls treated with R-da-EPOCH.
III. To categorize and compare the cell-of-origin by gene expression profiling (GEP) gene expression-based classification (GCB, activated B-cell-like, unclassifiable) to immunohistochemistry (IHC) classification (GCB, non-GCB), estimate the discordant classification, and correlate each biological classification (IHC and GEP) with treatment response rates and survival.
IV. To calculate the percentage of participants who receive two or more cycles of R-da-EPOCH, and are able to continue on a minimum dose level of cyclophosphamide of -1 and above after dose adjustments for hematologic toxicities.
- To determine the average number of days per cycle participants are able to stay on planned dose of ibrutinib at the recommended phase II dose (RP2D).
VI. To assess the effect of ibrutinib and R-da-EPOCH on levels of circulating tumor deoxyribonucleic acid (DNA).
VII. To assess the effect and degree of ibrutinib and R-da-EPOCH on T-cell receptor signaling via ITK inhibition.
VIII. To assess the effect of ibrutinib and R-da-EPOCH on B-cell receptor signaling pathway including BTK activity in ARL.
IX. To evaluate the soluble cytokine response to ibrutinib and R-da-EPOCH. X. To characterize the pharmacokinetics of doxorubicin, etoposide, and vincristine in the presence of ibrutinib, and vice versa, and assess the clinical relevance of any drug-drug interaction and correlate with pharmacodynamics outcomes.
OUTLINE: This is a dose escalation study of ibrutinib.
Patients receive rituximab intravenously (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 orally (PO) daily on days 1-5, cyclophosphamide IV over 1 hour on day 5, and ibrutinib PO once daily (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 subcutaneously (SC) from 1 calendar day up to 48 hours or filgrastim SC beginning on day 6 for up to 10 days until absolute neutrophil count (ANC) is satisfactory.
After completion of study treatment, patients are followed up every 3 months for 2 years, and then every 6 months for up to 5 years.
- Conditions
- AIDS-Related Lymphoma, Ann Arbor Stage II Diffuse Large B-Cell Lymphoma, Ann Arbor Stage III Diffuse Large B-Cell Lymphoma, Ann Arbor Stage IV Diffuse Large B-Cell Lymphoma
- Being tested
- Cyclophosphamide, Doxorubicin Hydrochloride, Etoposide, Filgrastim, Ibrutinib
- Medical subject headings
- Lymphoma, AIDS-Related
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CyclophosphamideDrug
Also called (-)-Cyclophosphamide, 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate, Asta B 518, B 518
Given IV
Also called 5,12-Naphthacenedione, 10-[(3-amino-2,3,6-trideoxy-alpha-L-lyxo-hexopyranosyl)oxy]-7,8, 9,10-tetrahydro-6,8,11-trihydroxy-8-(hydroxyacetyl)-1-methoxy-, hydrochloride, (8S-cis)- (9CI), ADM, Adriacin, Adriamycin
Given IV
EtoposideDrug
Also called Demethyl Epipodophyllotoxin Ethylidine Glucoside, EPEG, Lastet, Toposar
Given IV
FilgrastimBiological
Also called Filgrastim Biosimilar Filgrastim-sndz, Filgrastim Biosimilar Tbo-filgrastim, Filgrastim XM02, Filgrastim-aafi
Given SC
IbrutinibDrug
Also called BTK Inhibitor PCI-32765, CRA 032765, CRA-032765, CRA032765
Given PO
Laboratory Biomarker AnalysisOther
Correlative studies
PegfilgrastimBiological
Also called Cegfila, Dulastin, Dyrupeg, Filgrastim SD-01
Given SC
Correlative studies
PrednisoneDrug
Also called .delta.1-Cortisone, 1, 2-Dehydrocortisone, Adasone, Cortancyl
Given PO
RituximabBiological
Also called ABP 798, ABP-798, ABP798, BI 695500
Given IV
Also called Kyocristine, Leurocristine Sulfate, Leurocristine, sulfate, Oncovin
Given IV
| Study group | Role | What they receive |
|---|---|---|
| Treatment (R-da-EPOCH) | Experimental | Patients 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. Receives: Drug: Cyclophosphamide; Drug: Doxorubicin Hydrochloride; Drug: Etoposide; Biological: Filgrastim; Drug: Ibrutinib; Other: Laboratory Biomarker Analysis; Biological: Pegfilgrastim; Other: Pharmacological Study; Drug: Prednisone; Biological: Rituximab; Drug: Vincristine Sulfate |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: Up to 21 days
Secondary outcomes (17)
Incidence of Adverse Events Graded Using Common Terminology Criteria for Adverse Events Version 4.0
Toxicity data will be presented by type and severity for each dose cohort. Incidence of toxicity related dose reductions and treatment discontinuations will be summarized for each dose group.
Measured: Up to 5 years
Complete Response Rates
The complete response rates and their corresponding 95% confidence intervals will be calculated for participants with AIDS-related lymphomas (ARL) treated with combination ibrutinib and rituximab (R)-dose adjusted (da)-etoposide, prednisone, vincristine sulfate, cyclophosphamide and doxorubicin hydrochloride (EPOCH).
Response is currently assessed on the basis of clinical, radiologic, and pathologic (i.e., bone marrow) criteria. Radiologic response will be based on the Lugano Classification.
Complete metabolic response with Score 1, 2, or 3 with or without a residual mass on 5PS. Partial metabolic response with Score 4 or 5† with reduced uptake compared with baseline and residual mass(es) of any size. Overall Response (OR) consists of complete response and partial response.
Measured: Up to 5 years
Progression Free Survival (PFS)
PFS will be estimated using Kaplan Meier method, as well as, their corresponding 95% confidence intervals.
Progressive disease requires at least 1 of the following Perpendicular diameters: An individual node/lesion must be abnormal with: longest diameter 1.5 cm and Increase by 50% from perpendicular diameters nadir and an increase in longest diameter or shortest diameter from nadir 0.5 cm for lesions 2 cm 1.0 cm for lesions 2 cm. In the setting of splenomegaly, the splenic length must increase by 50% of the extent of its prior increase beyond baseline (e.g., a 15-cm spleen must increase to 16 cm). If no prior splenomegaly, must increase by at least 2 cm from baseline.
Measured: 1 year
Progression Free Survival (PFS)
PFS will be estimated using Kaplan Meier method, as well as, their corresponding 95% confidence intervals.
Progressive disease requires at least 1 of the following Perpendicular diameters: An individual node/lesion must be abnormal with: longest diameter 1.5 cm and Increase by 50% from perpendicular diameters nadir and an increase in longest diameter or shortest diameter from nadir 0.5 cm for lesions 2 cm 1.0 cm for lesions 2 cm. In the setting of splenomegaly, the splenic length must increase by 50% of the extent of its prior increase beyond baseline (e.g., a 15-cm spleen must increase to 16 cm). If no prior splenomegaly, must increase by at least 2 cm from baseline.
Measured: 2 years
Overall Survival (OS)
OS will be estimated using Kaplan Meier method, as well as, their corresponding 95% confidence intervals.
Measured: 1 year
Overall Survival (OS)
OS will be estimated using Kaplan Meier method, as well as, their corresponding 95% confidence intervals.
Measured: 2 years
Response by Lymphoma Cell-of-origin (COO) Assessment
Responses are tabulated by gene expression profiling (GEP) (germinal center B-cell [GCB], activated B-cell [ABC], unclassifiable) and immunohistochemistry [IHC] (GCB, non-GCB).
Measured: Up to 5 years
Percentage of Participants Who Receive Two or More Cycles of Combination Chemotherapy, and Are Able to Continue on a Minimum Dose Level of Cyclophosphamide of -1 and Above After Dose Adjustments
Hematologic toxicities will be calculated.
Measured: Up to 5 years
Average Number of Days Per Cycle Participants Are Able to Stay on Planned Dose of Ibrutinib
Average number of days will be calculated.
Measured: Up to 5 years
Changes in the Levels of Human Immunodeficiency Virus (HIV)-1 Viral Reservoirs
Descriptive statistics will be used to evaluate the changes and will be compared with treatment completion. If there are sufficient data, the binomial test of proportions will be used to test if the long term viral reservoir is either undetectable or below baseline in at least half of the participants.
Measured: Baseline up to 5 years
Changes in Epstein-Barr Virus (EBV) Viral Loads
Descriptive statistics will be used to evaluate the changes and compared with treatment completion. If there are sufficient data, the binomial test of proportions will be used to test if the long term viral reservoir is either undetectable or below baseline in at least half of the participants.
Measured: Baseline up to 5 years
Effect of Treatment on HIV Latency Reservoirs
Will be correlated with degree of ITK inhibition and Pearson or Spearman correlation coefficients will be used, as appropriate.
Measured: Up to 5 years
Effect of Treatment on B-cell Receptor Signaling Pathway Including BTK Activity
Descriptive statistics will be used.
Measured: Up to 5 years
Effect of Treatment on T-cell Receptor Signaling Via ITK Activity.
Descriptive statistics will be used.
Measured: Up to 5 years
Soluble Cytokine Response to Treatment
Descriptive statistics will be used.
Measured: Up to 5 years
Pharmacokinetics (PK) Parameters Assessment for Ibrutinib, Doxorubicin Hydrochloride, Etoposide, and Vincristine Sulfate
Relevant individual PK parameters will be estimated using non-compartmental or compartmental PK methods with the software WinNonlin. The PK variables will be tabulated and descriptive statistics (e.g., geometric means and coefficients of variation) and compared across dose levels (if applicable) using nonparametric statistical testing techniques. PK parameters (i.e., steady state concentration [Css], clearance [Cl], and area under the curve [AUC]) will be correlated with pharmacodynamics effects using nonparametric statistical testing techniques.
Measured: Up to 5 years
Survival by Lymphoma Cell-of-origin (COO) Assessment
Survival rates (PFS and OS at 1 year and 2 years) are reported by gene expression profiling (GEP) (germinal center B-cell [GCB], activated B-cell [ABC], unclassifiable) and immunohistochemistry [IHC] (GCB, non-GCB).
Measured: up to 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Jul 2017
- Study start16 Mar 2018
- Primary completion10 Oct 2024
- Study completion16 Jul 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for AIDS-Related LymphomaStudies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 46 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Ida C Wong-Sefidan, Principal investigator, AIDS Malignancy Consortium
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03220022
- Sponsor's protocol ID
- NCI-2017-01240
- Other IDs
- NCI-2017-01240, AMC-101, AMC-101, UM1CA121947
- Status last verified
- Jul 2026
- First submitted
- 17 Jul 2017
- Last updated
- 11 Aug 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No