Phase 2
N=3
Vorinostat and Combination Chemotherapy With Rituximab in Treating Patients With HIV-Related Diffuse Large B-Cell Non-Hodgkin Lymphoma or Other Aggressive B-Cell Lymphomas
AIDS-Related Plasmablastic Lymphoma · AIDS-Related Primary Effusion Lymphoma · Ann Arbor Stage I Diffuse Large B-Cell Lymphoma · Ann Arbor Stage I Grade 3 Follicular Lymphoma · Ann Arbor Stage II Diffuse Large B-Cell Lymphoma
Bottom Line
View on ClinicalTrials.gov: NCT01193842 ↗Enrolled (actual)
3
Serious AEs
50.5%
Results posted
Jun 2018
Primary outcome: Primary: Percentage of Participants With Complete Response (CR) as Assessed by Response Evaluation Criteria in Solid Tumors (Phase II) — 67.5; 76.2 percentage of participants
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- Cyclophosphamide (Drug); Doxorubicin Hydrochloride (Drug); Etoposide (Drug); Laboratory Biomarker Analysis (Other); Pharmacological Study (Other); Prednisone (Drug); Rituximab (Biological); Vincristine Sulfate (Drug); Vorinostat (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- National Cancer Institute (NCI)
- Primary completion
- Nov 2016
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Percentage of Participants With Complete Response (CR) as Assessed by Response Evaluation Criteria in Solid Tumors (Phase II) |
67.5; 76.2 | — |
| PRIMARY Percentage of Participant Experiencing Adverse Events (AEs) for Each Treatment Arm as Assessed by Common Terminology Criteria for Adverse Events Version 4.0 (CTCAE v4.0) (Phase II) |
28.9; 20.0; 37.8; 28.9; 20.0; 31.1 | — |
| PRIMARY Recommended Phase II Dose of Vorinostat Determined According to Dose-limiting Toxicities Graded Using Common Terminology Criteria for Adverse Events Version 4.0 (CTCAE v4.0) (Phase I) |
300 | — |
| SECONDARY Change in CD8 Cell Counts (Phase I) |
35.5; -115; -172; -164.5; 211; -81 | — |
| SECONDARY Changes in Absolute CD4 Cell Counts (Phase I) |
92; -9; -218; -39; -29; -190 | — |
| SECONDARY Changes in Epstein-Barr Virus (EBV) Viral Load |
-0.61; 0; 0; -2436.1; -2.9; -0.28 | — |
| SECONDARY Changes in Human Herpes Virus (HHV)-8 Viral Load |
0; 0; 0; 0 | — |
| SECONDARY Changes in Human Immunodeficiency Virus (HIV) Viral Load |
-20; -25; -87; -22.5; -20; -18 | — |
| SECONDARY Event-free Survival (EFS) (Phase II) |
75.6; 82.2 | — |
| SECONDARY Overall Survival (OS) (Phase II) |
77.6; 86.7 | — |
| SECONDARY Change in Plasma Associated Human Immunodeficiency Virus (HIV)-1 Ribonucleic Acid (RNA) (Phase I) |
-14518; -12.5; 28; -4517; 0; 0 | — |
| SECONDARY Pharmacokinetic Clearance (Phase I) |
78.6; 76.0; 3.0; 2.4; 22.4; 16.8 | — |
| SECONDARY Tumor Response (Phase I) |
83.3; 83.3; 100; 16.7; 16.7; 0 | — |
Summary
This partially randomized phase I/II trial studies the side effects and the best dose of vorinostat when given together with combination chemotherapy and rituximab to see how well it works compared to combination chemotherapy alone in treating patients with human immunodeficiency virus-related diffuse large B-cell non-Hodgkin lymphoma or other aggressive B-cell lymphomas. Vorinostat may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy 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. Monoclonal antibodies, such as rituximab, may interfere with the ability of cancer cells to grow and spread. Giving vorinostat together with combination chemotherapy and rituximab may kill more cancer cells.
Eligibility Criteria
Inclusion Criteria
- Participants with histologically or cytologically documented diffuse large B-cell lymphoma (DLBCL) must meet at least 1 of the following risk criteria:
- Age-adjusted International Prognostic Index (IPI) score: 2-3
- Ki-67 >= 80%
- Histologically, or cytologically documented activated B-cell-like (ABC, also known as post-GCB) subtype
- Double hit variant, defined as having v-myc avian myelocytomatosis viral oncogene homolog (MYC) gene rearrangement in the presence of B-cell chronic lymphocytic leukemia (CLL)/lymphoma (BCL) 2 or BCL6 gene rearrangement
- Other aggressive non-DLBCL non-Burkitt non-Hodgkin B-cell lymphoma variants as defined by the 2008 World Health Organization (WHO) classification, including rare CD20 negative B-cell lymphomas (i.e. plasmablastic lymphoma, and primary effusion lymphoma) are also eligible; grade 3B follicular lymphoma is also eligible as long as one the above risk criteria is met
- Participants who are untreated or who received a maximum of one (1) cycle of combination chemotherapy, including rituximab-containing regimens, prior are eligible; the start of previous chemotherapy cycle must occur at least 21 days prior to beginning treatment under this protocol, and such cycle will count towards the total maximum of 6 cycles under this study
- Documentation of HIV infection at any time prior to study entry; documentation may be molecular (detectable viral ribonucleic acid [RNA] by polymerase chain reaction [PCR]), serologic (positive enzyme-linked immunosorbent assay [ELISA] and positive Western blot), or other federally approved licensed HIV test; prior documentation of HIV seropositivity is acceptable
- All stages of disease
- Measurable or non-measurable tumor parameter(s); non-measurable tumor parameters are defined as not having bidimensional measurements (e.g., gastric or marrow involvement), but can be followed for response by other diagnostic tests such as gallium, positron emission tomography (PET) imaging, and/or bone marrow biopsy
- Performance status (PS) 0, 1, or 2 per the Eastern Cooperative Oncology Group (ECOG) performance status scale (Karnofsky performance score >= 50%)
- Able to provide informed consent
- Total bilirubin = 1.2 due to hepatic involvement by tumor for the initial dose of EPOCH drug adjustment
- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) = = 60 mL/min, unless secondary to renal involvement by lymphoma; for creatinine clearance = 1,000/mm^3
- Platelets >= 75, 000/mm^3 (unless these parameters are abnormal secondary to lymphomatous involvement of bone marrow); all participants must cease colony-stimulating factor therapy at least 24 hours prior to institution of cycle 1 chemotherapy
- Left ventricular ejection fraction (LVEF) that is at or above the lower institutional limits of normal, as assessed by multiple gated acquisition (MUGA) scan or echocardiogram within the 6 weeks prior to registration
- Concurrent radiation, with or without steroids, or steroids alone for emergency conditions secondary to lymphoma (i.e. cord compression, etc.) will be permitted
- Female participants must have a negative pregnancy test within 7 days of entering into the study; both men and women of child bearing potential must agree to use adequate methods of contraception for the duration of the treatment; women must avoid pregnancy, and men must avoid fathering children while in the study and for 6 months following the last study drug treatment
- Participants on an antiretroviral regimen should be receiving treatment that is in accordance with the current International acquired immune deficiency syndrome (AIDS) Society guidelines; the specific agents are at the discretion of the investigator and use of agents currently available on an expanded access basis is allowed but use of experimental antiretroviral agents or those containing zidovudine (including Combivir and Trizivir) are prohibited; changes to highly active anti-retroviral therapy
Data sourced from ClinicalTrials.gov (NCT01193842). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.