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Feasibility Study of CO-administering Combination Antiretroviral Therapy (cART) and R-EPOCH Chemotherapy for the Management of Acquired Immunodeficiency Syndrome (AIDS)-Related Lymphoma

Phase 2
18 Years
Open (Enrolling)
Lymphoma, AIDS Related, HIV Infections

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Trial Information

Feasibility Study of CO-administering Combination Antiretroviral Therapy (cART) and R-EPOCH Chemotherapy for the Management of Acquired Immunodeficiency Syndrome (AIDS)-Related Lymphoma

Study Design & Duration This is a prospective, single-arm, multi-centre, phase II trial of
immuno-chemotherapy (rituximab and EPOCH) with mandatory combination antiretroviral therapy
for initial treatment of AIDS-related lymphoma. Patients diagnosed with previously-untreated
AIDS-related diffuse large B-cell lymphoma will be eligible for this trial. Patients are
eligible regardless of whether they have previously been treated with or are naïve to
antiretroviral therapy. The total sample size of 18 patients is required to determine the
feasibility of co-administering cART and chemotherapy as measured by adequate adherence to
the antiretroviral regimen.

Patients will receive EPOCH and rituximab chemotherapy for 6 cycles each given every 21
days. Day 1 of each cycle will consist of an infusion of rituximab followed by the
initiation of a 96-hour continuous infusion of etoposide, doxorubicin, and vincristine and
oral prednisone. Cyclophosphamide will be administered on Day 5 with initial dose based on
initial CD4+ cell count to minimize hematologic toxicity.

Combination antiretroviral therapy will be administered to all patients enrolled in the
trial. Patients already responding to their current cART regimen will continue with the same
therapy. Otherwise, patients can be initiated on a preferred regimen of tenofovir (TDF),
emtricitabine (FTC), and efavirenz (EFV) according to the US Department of Health and Human
Services (DHHS) guidelines. Patients initiated on the preferred regimen of TDF/FTC/EFV will
start the antiretroviral treatments on Day 7 of the trial, after the first cycle of R-EPOCH
is administered. Treatment will subsequently be continued for the duration of the trial and
thereafter, according to the discretion of the treating physician.

The primary endpoint for this feasibility study will be medication adherence to cART
treatment. "Acceptable adherence" will be defined as the proportion of patients able to
complete >90% of all prescribed cART doses during the course of chemotherapy as measured by
pill counts. As previously reported, study participants will be asked to bring their pill
bottles to clinic prior to each chemotherapy cycle (every three weeks) so that remaining
pills can be counted by the participating study nurse/pharmacist. The number of missed doses
will be computed from the difference between the actual and expected number of pills
remaining in the bottle. Secondary outcomes include the toxicity of the combination therapy,
as measured by adverse events graded according to the Common Terminology Criteria for
Adverse Events (CTCAE) Version 3.0. CD4+ cell counts and HIV-1 mRNA viral loads will be
obtained on all patients at baseline, following recovery from cycles 3 and 6, and every
three months thereafter for two years. Secondary outcomes will also include complete and
partial lymphoma response rate, progression-free survival, and overall survival, all defined
by International Working Group criteria. The pharmacokinetics of etoposide, vincristine and
doxorubicin will be studied in the patients initiating the preferred antiretrovirals
TDF/3TC/EFV on Day 7 of the protocol (after completion of the first cycle of R-EPOCH). Thus
the analysis of PK interactions will be on this subgroup of patients receiving a uniform
treatment strategy. Pharmacokinetics will be assessed with the first cycle (when
chemotherapy is given alone) and subsequent cycle of R-EPOCH (when chemotherapy is given
with cART).

Study administration and data collection will occur under the auspices of the Ontario
Clinical Oncology Group (OCOG). OCOG operates from within the Clinical Trials Methodology
Group at the Henderson Research Centre in Hamilton and is co-directed by oncologists at the
Juravinski Cancer Centre and Toronto Sunnybrook Cancer Centres. OCOG has a well-established
research environment to guide the administration of this trial across four unique clinical
sites across Canada. The clinical sites for the study include Toronto Sunnybrook Regional
Cancer Centre (TSRCC), Princess Margaret Hospital (PMH), St. Michael's Hospital (SMH), and
at the St. Paul's Hospital (SPH) in Vancouver. Each clinical site is expected to enroll 1-4
patients per year. An overall accrual rate of 8-10 patients per year is expected. Therefore,
it will be possible to register 18 patients within 2 years of study initiation. For the
individual patient, the chemotherapy treatment duration is 18 weeks. Following this phase of
therapy (18 weeks), individual patients will be followed every 3 months for an additional 2

Inclusion Criteria:

1. HIV seropositivity

2. Biopsy diagnosis of a CD20+ diffuse large B-cell lymphoma or variants (including
mediastinal (thymic) large B-cell lymphoma and plasmablastic lymphoma), atypical
Burkit/Burkitt-like lymphoma, or Burkitt lymphoma diagnosed according to the World
Health Organization (WHO) classification

3. Age 18 years or older

Exclusion Criteria

1. Performance status ≥3 according to ECOG (Zubrod) scale (see Appendix I)

2. Known primary central nervous system lymphoma or parenchymal brain involvement with

3. Non-measurable disease by physical examination or radiographic evaluation

4. Absolute CD4+ cell count <50 cells/mm3 within 3 months prior to trial initiation

5. Inadequate hepatic function (total bilirubin ≥35 µmol/L, alkaline phosphatase ≥2 xUL
normal, AST/ALT ≥2 xUL normal) unless directly attributable to lymphoma or known
Hepatitis B or C co-infection.

6. Inadequate renal function (serum creatinine ≥125µmol/L) unless directly attributable
to lymphoma

7. Inadequate haematological function (haemoglobin ≤85 g/L, absolute neutrophil count
≤1000 cells/mm3, platelet count ≤75,000 cells/mm3) unless directly attributable to
lymphoma or autoimmune thrombocytopenia.

8. Evidence of left ventricular (LV) dysfunction (ejection fraction ≤ 50%) in patients
over the age of 60 or in patients with a prior history of hypertension, congestive
heart failure, peripheral vascular disease, cerebrovascular disease, coronary artery
disease, or cardiac arrhythmia

9. Pregnant or lactating women who intend to breast-feed during the trial period

10. Men of reproductive potential and women of childbearing potential who are not using
or not willing to use effective contraception

11. Known intolerance to the prescribed chemotherapy or antiretroviral drugs

12. Life-expectancy ≤ 3 months

13. Geographically inaccessible for follow-up

Type of Study:


Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

The primary outcome for this feasibility study will be medication adherence. Acceptable adherence, defined as compliance to ≥90% of all prescribed doses of cART during the course of chemotherapy, will be measured by pill counting and patient self-report

Outcome Time Frame:

4 -6 weeks after 6 cycles of R-EPOCH

Safety Issue:


Principal Investigator

Matthew Cheung, Dr. .

Investigator Role:

Principal Investigator

Investigator Affiliation:

Odette Cancer Centre


Canada: Health Canada

Study ID:




Start Date:

February 2008

Completion Date:

March 2013

Related Keywords:

  • Lymphoma, AIDS Related
  • HIV Infections
  • Lymphoma Large B Cell Diffuse
  • Acquired Immunodeficiency
  • Acquired Immunodeficiency Syndrome
  • HIV Infections
  • Immunologic Deficiency Syndromes
  • Lymphoma
  • Lymphoma, AIDS-Related