Bethesda, Maryland 20892


Purpose:

Background: - 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 CT and 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.


Study summary:

Background: This is a study to investigate in a preliminary fashion the feasibility of short course chemotherapy to patients with HIV-associated non-Hodgkin's lymphoma (HIV-NHL). This study will investigate if the paradigm for treatment can be successfully changed from a standard of 6 cycles to one cycle beyond complete remission with 6 total allowable cycles. Objective: To assess with 90 percent probability that at least 50 percent of patients treated with short-course EPOCH-R will be progression free at one year. Eligibility: Aggressive CD20 positive DLBCL. HIV+ serology. All stages (I-IV) of disease. ECOG Performance status 0-4. NHL previously untreated with cytotoxic chemotherapy. Age greater than or equal to 18 years. May not be pregnant or nursing. May not have received previous rituximab. Design: Patients will be treated every three weeks with a combination of EPOCH and rituximab for one cycle beyond CR/CRu by CT scan of all detectable tumors for a minimum of three and maximum of six cycles. Following cycle 2, CT, positron emission tomography scans (PET), and bone marrow biopsies (if initially positive) will be performed. At the conclusion of the study, we will estimate whether the number of cycles can be reduced using the paradigm. If the cumulative number of patients to relapse exceeds 25 percent by 6 months, the study will be closed. Following the completion of chemotherapy, restaging will be performed 2 months following the end of treatment, then every 3 months for one year, every 6 months for one year, then every 12 months until relapse, death, or loss to follow up. Antiretroviral therapy (ART) will be given concurrently with treatment regimen. To study the effects of treatment approach on parameters of HIV disease, measurements of CD4 cells and viral loads will be made at baseline and at the completion of therapy, and then 2 months following the end of treatment, and then every 3-6 months for a total of 24 months following chemotherapy.


Criteria:

- INCLUSION CRITERIA: Aggressive CD20 positive Diffuse Large B-cell lymphoma confirmed by Laboratory of Pathology, NCI. Note: Patients with aggressive B-cell lymphoma of the plasmablastic lymphoma sub-type who do not have surface CD20 expression, are also eligible. HIV + serology. All stages (I-IV) of disease. ECOG Performance status 0-4 NHL previously untreated with cytotoxic chemotherapy; however, patients 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 methotrexte (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 patients for whom these abnormalities are felt to be due to protease inhibitor therapy - AST and ALT less than or equal to 3x ULN (AST and ALT less than or equal to 6x ULN for patients on hyperalimentation for whom these abnormalities are felt to be due to the hyperalimentation) - ANC greater than or equal to 1000/mm(3) - Platelet greater than or equal to 75,000/mm(3) (unless impairment due to ITP) Ability of patient to provide informed consent. EXCLUSION CRITERIA: 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 SC-EPOCH-R. - Examples include, but are not limited to: - Severe AIDS-related wasting - Sever intractable diarrhea - Active inadequately treated opportunistic infection of the CNS - Primary CNS lymphoma Primary CNS lymphoma


Study is Available At:


Original ID:

010030


NCT ID:

NCT00006436


Secondary ID:

01-C-0030


Study Acronym:


Brief Title:

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


Official Title:

Short-Course EPOCH-Rituximab in Untreated CD-20+ HIV-Associated Lymphomas


Overall Status:

Recruiting


Study Phase:

Phase 2


Genders:

N/A


Minimum Age:

18 Years


Maximum Age:

100 Years


Quick Facts

Healthy Volunteers
Oversight Has DMC
Study Is FDA Regulated
Study Is Section 801
Has Expanded Access

Study Source:

National Institutes of Health Clinical Center (CC)


Oversight Authority:

United States: Federal Government


Reasons Why Stopped:


Study Type:

Interventional


Study Design:


Number of Arms:

1


Number of Groups:

0


Total Enrollment:

80


Enrollment Type:

Anticipated


Overall Contact Information

Official Name:Mark J Roschewski, M.D.
Principal Investigator
National Cancer Institute (NCI)
Primary Contact:A. Nicole Lucas
(240) 760-6252
lucasan2@mail.nih.gov
Backup Contact:Mark J Roschewski, M.D.
(240) 760-6183
mark.roschewski@nih.gov

Study Dates

Start Date:January 29, 2001
Completion Date:March 31, 2022
Completion Type:Anticipated
Primary Completion Date:March 31, 2021
Primary Completion Type:Anticipated
Verification Date:May 2, 2019
Last Changed Date:October 8, 2019
First Received Date:November 3, 2000

Study Outcomes

Outcome Type:Primary Outcome
Measure:Progression free survival
Time Frame:Time of progressive disease
Safety Issues:False
Description:Disease progression as indicated by imaging scans and blood tests (CD4 cells and viral loads) at baseline, at the completion of therapy,2months following the end of treatment, and every 3-6 months (for a total of 24 months) following therapy.

Study Interventions

Intervention Type:Biological
Name:Rituximab
Description:2 doses of rituximab every cycle: first dose on Day 1 and 2nd dose on Day 5
Arm Name:1
Intervention Type:Biological
Name:filgrastim
Description:Figrastim day 6 until ANC reaches 5000 after the nadir, every cycle
Arm Name:1
Intervention Type:Drug
Name:EPOCH
Description:combination chemotheray: EPOCH every 3 weeks for minimum of 3 cycles and max of 6 cycles
Arm Name:1

Study Arms

Study Arm Type:Experimental
Arm Name:1
Description:Combo chemo and biological therapy

Study Agencies

Agency Class:NIH
Agency Type:Lead Sponsor
Agency Name:National Cancer Institute (NCI)

Sample and Retention Information

There are no available Sample and Retention Information

Study References

Reference Type:Reference
Citation:Kaplan LD, Straus DJ, Testa MA, Von Roenn J, Dezube BJ, Cooley TP, Herndier B, Northfelt DW, Huang J, Tulpule A, Levine AM. Low-dose compared with standard-dose m-BACOD chemotherapy for non-Hodgkin's lymphoma associated with human immunodeficiency virus infection. National Institute of Allergy and Infectious Diseases AIDS Clinical Trials Group. N Engl J Med. 1997 Jun 5;336(23):1641-8.
PMID:9171066
Reference Type:Reference
Citation:Tirelli U, Spina M, Vaccher E, Errante D, Tavio M, Simonelli C, Sinicco A, Gastaldi R, Rossi G, Rizzardini G, et al. Clinical evaluation of 451 patients with HIV related non-Hodgkin's lymphoma: experience on the Italian cooperative group on AIDS and tumors (GICAT). Leuk Lymphoma. 1995 Dec;20(1-2):91-6.
PMID:8750628
Reference Type:Reference
Citation:Levine AM. Epidemiology, clinical characteristics, and management of AIDS-related lymphoma. Hematol Oncol Clin North Am. 1991 Apr;5(2):331-42. Review.
PMID:2022597

Data Source: ClinicalTrials.gov

Date Processed: November 18, 2019

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