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

Sponsor:	National Cancer Institute (NCI)
Information provided by:	National Institutes of Health Clinical Center (CC)
ClinicalTrials.gov Identifier:	NCT00006436

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.

Condition	Intervention	Phase
AIDS Related Lymphoma HIV Infection	Biological: Rituximab Biological: filgrastim Drug: cyclophosphamide Drug: doxorubicin hydrochloride Drug: etoposide Drug: vincristine sulfate	Phase 2

Study Type:	Interventional
Study Design:	Masking: Open Label Primary Purpose: Treatment
Official Title:	Short-Course EPOCH-Rituximab for Untreated CD-20+ HIV-Associated Lymphomas

Resource links provided by NLM:

Genetics Home Reference related topics: complement factor I deficiency

MedlinePlus related topics: Cancer HIV/AIDS Lymphoma Nuclear Scans

Drug Information available for: Cyclophosphamide Vincristine sulfate Doxorubicin Doxorubicin hydrochloride Etoposide Etoposide phosphate Filgrastim Lenograstim Granulocyte colony-stimulating factor Rituximab

U.S. FDA Resources

Further study details as provided by National Institutes of Health Clinical Center (CC):

Primary Outcome Measures:

Progression-free survival at 1 year after completion of study treatment [ Designated as safety issue: No ]

Secondary Outcome Measures:

Toxicity during and 1 year after completion of study treatment. [ Designated as safety issue: Yes ]
Response rate and duration at completion of study treatment and 5 years later. [ Designated as safety issue: No ]
Ability of positron emission tomography (PET) scans to predict freedom from relapse at completion of study treatment and 5 years later. [ Designated as safety issue: No ]
Effects of short course etoposide, vincristine, cyclophosphamide, doxorubicin, and rituximab (SC-EPOCH-R) on CD4 cell depletion and recovery at completion of study treatment and 18 months later. [ Designated as safety issue: No ]
Response to antiretroviral therapy following SC-EPOCH-R 18 months after completion of study treatment. [ Designated as safety issue: No ]

Estimated Enrollment:	80
Study Start Date:	October 2000
Estimated Study Completion Date:	March 2013
Estimated Primary Completion Date:	March 2013 (Final data collection date for primary outcome measure)

Intervention Details:

N/A

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Eligibility

Ages Eligible for Study:	4 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

INCLUSION CRITERIA:

Aggressive CD20 positive Diffuse Large B-cell lymphoma confirmed by Laboratory of Pathology, NCI.

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 4 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

Pediatric patients: Age-adjusted normal serum creatinine according to the following table or a creatinine clearance greater than 60 ml/min/1.73 m(2).

Less than or equal to 5 age (years), 0.8 Maximum serum creatinine

Greater than 5, less than or equal to 10 age (years), 1.0 Maximum serum creatinine

Greater than 10, less than or equal to 15 age (years), 1.2 Maximum serum creatinine

Greater than 15 age (years), 1.5 Maximum serum creatinine

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 or parent/guardian to provide informed consent.

EXCLUSION CRITERIA:

Previous rituximab

Pregnancy or nursing.

Doxorubicin, etoposide, vincristine and cyclophosphamide are teratogenic and may be excreted in milk.
Antiretroviral therapy is indicated during pregnancy and nursing.

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

Concurrent anti-retroviral therapy during EPOCH therapy.

Primary CNS lymphoma.

Adolescents who do not freely assent

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00006436

Contacts

Contact: Margaret Shovlin, R.N.	(301) 594-6597	mshovlin@mail.nih.gov
Contact: Wyndham H Wilson, M.D.	(301) 435-2415	wilsonw@box-w.nih.gov

Locations

United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike	Recruiting
Bethesda, Maryland, United States, 20892
Contact: For more information at the NIH Clinical Center contact National Cancer Institute Referral Office (888) NCI-1937

Sponsors and Collaborators

National Cancer Institute (NCI)

Investigators

Principal Investigator:

Wyndham H Wilson, M.D.

National Cancer Institute (NCI)

More Information

Additional Information:

NIH Clinical Center Detailed Web Page This link exits the ClinicalTrials.gov site

Publications:

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.

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.

Levine AM. Epidemiology, clinical characteristics, and management of AIDS-related lymphoma. Hematol Oncol Clin North Am. 1991 Apr;5(2):331-42. Review.

Responsible Party:	Wyndham H. Wilson, M.D./National Cancer Institute, National Institutes of Health
ClinicalTrials.gov Identifier:	NCT00006436 History of Changes
Obsolete Identifiers:	NCT00020384
Other Study ID Numbers:	010030, 01-C-0030
Study First Received:	November 3, 2000
Last Updated:	March 14, 2012
Health Authority:	United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):

AIDS
Malignancy
Antiretroviral
Chemotherapy
Monoclonal

Additional relevant MeSH terms:

HIV Infections
Acquired Immunodeficiency Syndrome
Lymphoma
Lymphoma, Non-Hodgkin
Lymphoma, AIDS-Related
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases
Neoplasms by Histologic Type

Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Lymphoma, B-Cell
Cyclophosphamide
Rituximab
Doxorubicin
Etoposide
Vincristine
Lenograstim
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on May 20, 2012