EPOCH and Rituximab to Treat Non-Hodgkin's Lymphoma in Patients With HIV Infection

NCT00006436 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: 01003001-C-0030
• Study Type: interventional
• Target: 68
• Locations: 1 country
• Sites: 1

Brief Summary

Background:

• Human immunodeficiency virus (HIV)-infected patients have a weakened immune system, and chemotherapy, which is used to treat lymphoma, probably causes further damage to the immune system.
• Limiting the amount of immune damage due to chemotherapy might decrease the number of infections and the risk of developing cancer in the future in HIV-infected patients with non-Hodgkin's lymphoma. Objectives:
• To determine whether reducing the total amount of chemotherapy using a specific combination of drugs called EPOCH-R (etoposide, doxorubicin, vincristine, cyclophosphamide and rituximab) will rid the body of lymphoma quickly while decreasing the risk of infections and future cancers.
• To determine whether the lymphoma will remain undetectable for at least one year if treatment is stopped one cycle after the patient enters remission. Eligibility:
• Patients with non-Hodgkin's lymphoma and HIV infection 4 years of age and older who have not been treated previously with rituximab or cytotoxic chemotherapy. Design:
• Patients receive EPOCH-R in 3-week treatment cycles for at least three and no more than six cycles.
• The lymphoma is evaluated using computed tomography (CT) and positron emission tomography (PET) scans at the end of treatment cycles 2 and 3. A bone marrow biopsy is repeated after cycle 2 if a biopsy was initially positive on screening for participation in the study.
• Anti-HIV therapy is stopped before chemotherapy begins and is restarted when EPOCH-R treatment ends.
• Patients are monitored for treatment response with blood tests and imaging scans at baseline, when treatment ends, 2 months after treatment ends and then every 3 to 6 months for a total of 24 months following chemotherapy.

Conditions

Lymphoma, Large B-Cell, Diffuse; Lymphoma, AIDS-related

Keywords

AIDS; Malignancy; Antiretroviral; Chemotherapy; Monoclonal

Outcome Measures

Primary Outcomes (2)

• Median Progression Free Survival (PFS)

  PFS is the time interval from study entry to documented evidence of disease progression or death due to any cause. Progression is defined according to the Cheson response criteria. Disease progression is defined as increase of 25% or more in the sum of the products of the longest perpendicular diameters of all measured lesions compared to the smallest previous measurements, or the appearance of any new lesion(s). Confidence intervals were made, and a Kaplan-Meier curve of progression free survival was constructed.

  The participants were followed for a median of 15.4 years.

• Progression Free Survival at 1 Year

  PFS is the time interval from start of treatment to documented evidence of disease progression. Progression is defined according to the Cheson response criteria. Disease progression as indicated by imaging scans at one year following therapy. Disease progression is defined as increase of 25% or more in the sum of the products of the longest perpendicular diameters of all measured lesions compared to the smallest previous measurements, or the appearance of any new lesion(s).

  1 year

Secondary Outcomes (13)

• Number of Participants With ≥ Grades 3-5 Non-hematologic Toxicity

  Date treatment consent signed to date off study, approximately 209 months and 17 days.

• Median Overall Survival

  The participants were followed for survival for a median of 15.4 years.

• 1 Year Overall Survival

  1 year

• Median Duration of Complete Response/Complete Response Unconfirmed

  The participants were followed for duration of complete response or complete response unconfirmed for a median of 15.4 years.

• Percentage of Participants With CR/CRu Lasting 1 Year

  1 year

Other Outcomes (1)

• Number of Participants With Serious and/or Non-serious Adverse Events Assessed by the Common Toxicity Criteria (CTC v2.0)

  Date treatment consent signed to date off study, approximately 209 months and 17 days.

Study Arms (1)

Arm 1-Combination Chemo and Biological Therapy

EXPERIMENTAL

Combination chemo and biological therapy

Biological: Rituximab; Biological: Filgrastim; Drug: EPOCH

Interventions

Filgrastim BIOLOGICAL

Filgrastim day 6 until absolute neutrophil count (ANC) reaches 5000 after the nadir, every cycle

Also known as: Neupogen

Arm 1-Combination Chemo and Biological Therapy

EPOCH DRUG

combination chemotheray: EPOCH every 3 weeks for minimum of 3 cycles and max of 6 cycles

Also known as: etoposide, prednisone, vincristine, cyclophosphamide and doxorubicin hydrochloride

Arm 1-Combination Chemo and Biological Therapy

Rituximab BIOLOGICAL

2 doses of rituximab every cycle: first dose on Day 1 and 2nd dose on Day 5

Also known as: Rituxan

Arm 1-Combination Chemo and Biological Therapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Aggressive B-lymphocyte antigen CD20 (CD20) positive Diffuse Large B-cell lymphoma confirmed by Laboratory of Pathology, National Cancer Institute (NCI). Note: Participants with aggressive B-cell lymphoma of the plasmablastic lymphoma sub-type who do not have surface CD20 expression, are also eligible.
• Human immunodeficiency virus (HIV) + serology.
• All stages (I-IV) of disease.
• Eastern Cooperative Oncology Group (ECOG) Performance status 0-4
• Non-Hodgkin's Lymphoma (NHL) previously untreated with cytotoxic chemotherapy; however, participants may be entered if they have had prior cyclophosphamide for an urgent problem at diagnosis (e.g., epidural cord compression, superior vena cava syndrome) and/or a single dose of intrathecal methotrexate (MTX) at the time of the pre-treatment diagnostic lumbar puncture
• Age greater than or equal to 18 years
• Laboratory tests (unless impairment due to respective organ involvement by tumor):
• Creatinine less than or equal to 1.5 mg/dl or creatinine clearance greater than or equal to 50 ml/min
• Bilirubin less than 2.0 mg/dl, or total bilirubin less than or equal to 4.5 mg/dl with direct fraction less than or equal to 0.3 mg/dl in participants for whom these abnormalities are felt to be due to protease inhibitor therapy
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) less than or equal to 3x upper limit of normal (ULN) (AST and ALT less than or equal to 6x ULN for participants on hyperalimentation for whom these abnormalities are felt to be due to the hyperalimentation)
• Absolute neutrophil count (ANC) greater than or equal to 1000/mm(3)
• Platelet greater than or equal to 75,000/mm(3) (unless impairment due to Immune thrombocytopenic purpura (ITP)
• Ability of participant to provide informed consent.

You may not qualify if:

• Previous rituximab
• Pregnancy or nursing.
• \- Doxorubicin, etoposide, vincristine and cyclophosphamide are teratogenic and may be excreted in milk.
• Current clinical heart failure or symptomatic ischemic heart disease.
• Serious underlying medical condition or infection other than HIV that would contraindicate subcutaneous (SC)-rituximab, etoposide phosphate, prednisone, vincristine sulfate, cyclophosphamide, and doxorubicin hydrochloride (hydroxydaunorubicin (EPOCH-R).
• Examples include, but are not limited to:
• Severe Acquired immunodeficiency syndrome (AIDS)-related wasting
• Sever intractable diarrhea
• Active inadequately treated opportunistic infection of the central nervous system (CNS)
• Primary CNS lymphoma
• Primary CNS lymphoma

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (2)

• Kurtz DM, Scherer F, Jin MC, Soo J, Craig AFM, Esfahani MS, Chabon JJ, Stehr H, Liu CL, Tibshirani R, Maeda LS, Gupta NK, Khodadoust MS, Advani RH, Levy R, Newman AM, Duhrsen U, Huttmann A, Meignan M, Casasnovas RO, Westin JR, Roschewski M, Wilson WH, Gaidano G, Rossi D, Diehn M, Alizadeh AA. Circulating Tumor DNA Measurements As Early Outcome Predictors in Diffuse Large B-Cell Lymphoma. J Clin Oncol. 2018 Oct 1;36(28):2845-2853. doi: 10.1200/JCO.2018.78.5246. Epub 2018 Aug 20.

  PMID: 30125215 DERIVED

• Dunleavy K, Pittaluga S, Shovlin M, Steinberg SM, Cole D, Grant C, Widemann B, Staudt LM, Jaffe ES, Little RF, Wilson WH. Low-intensity therapy in adults with Burkitt's lymphoma. N Engl J Med. 2013 Nov 14;369(20):1915-25. doi: 10.1056/NEJMoa1308392.

  PMID: 24224624 DERIVED

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Lymphoma, AIDS-Related; Lymphoma, Large B-Cell, Diffuse; Acquired Immunodeficiency Syndrome; Neoplasms

Interventions

Rituximab; Filgrastim; Etoposide; Prednisone; Vincristine; Cyclophosphamide; Doxorubicin

Condition Hierarchy (Ancestors)

Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; HIV Infections; Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Slow Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Granulocyte Colony-Stimulating Factor; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Biological Factors; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Glucosides; Glycosides; Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Daunorubicin; Anthracyclines; Naphthacenes; Aminoglycosides

Results Point of Contact

• Title: Dr. Max Gordon
• Organization: National Cancer Institute

max.gordon@nih.gov

240-858-7151

Study Officials

• Max Gordon, M.D.

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: November 3, 2000
• First Posted: November 6, 2000
• Study Start: January 29, 2001
• Primary Completion: November 30, 2020
• Study Completion: January 18, 2024
• Last Updated: December 30, 2025
• Results First Posted: June 28, 2022

Record last verified: 2025-12

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 database of Genotypes and Phenotypes (dbGaP) through requests to the data custodians.

Locations

US (1)