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Randomized, Phase II Trial of CHOP vs. Oral Chemotherapy With Concomitant Antiretroviral Therapy in Patients With HIV-Associated Lymphoma in Sub-Saharan Africa

Phase 2
18 Years
Not Enrolling
AIDS-related Diffuse Large Cell Lymphoma, AIDS-related Diffuse Mixed Cell Lymphoma, AIDS-related Diffuse Small Cleaved Cell Lymphoma, AIDS-related Immunoblastic Large Cell Lymphoma, AIDS-related Lymphoblastic Lymphoma, AIDS-related Peripheral/Systemic Lymphoma, AIDS-related Small Noncleaved Cell Lymphoma, Stage III AIDS-related Lymphoma, Stage IV AIDS-related Lymphoma

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Trial Information

Randomized, Phase II Trial of CHOP vs. Oral Chemotherapy With Concomitant Antiretroviral Therapy in Patients With HIV-Associated Lymphoma in Sub-Saharan Africa


I. To compare the efficacy of standard cyclophosphamide, doxorubicin hydrochloride,
vincristine sulfate, and prednisone (CHOP) and an oral chemotherapy regimen for acquired
immune deficiency syndrome (AIDS)-related (AR)-non-Hodgkin lymphoma (NHL) in sub-Saharan
Africa with respect to overall survival (OS).


I. To compare the objectives response rate (ORR) of persons randomized to CHOP and oral

II. To compare the progression free survival (PFS) of persons randomized to CHOP and oral

III. To compare the safety and tolerance of persons randomized to CHOP and oral


I. To describe the rates of completion of therapy of persons randomized to CHOP and oral

II. To describe adherence to chemotherapy of persons randomized to CHOP and oral

III. To describe adherence to antiretroviral therapy of persons randomized to CHOP and oral

IV. To describe the effects of therapy on HIV control, as measured by cluster of
differentiation (CD)4 counts and HIV viral load.

V. To investigate correlates of survival.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients receive CHOP chemotherapy comprising cyclophosphamide intravenously (IV) on
day 1, doxorubicin hydrochloride IV on day 1, vincristine sulfate IV on day 1, and
prednisone orally (PO) on days 1-5. Treatment repeats every 3 weeks for up to 6 courses in
the absence of disease progression or unacceptable toxicity.

ARM II: Patients receive lomustine PO once daily (QD) on day 1 (courses 1 and 3 only),
etoposide PO QD on days 1-3, cyclophosphamide PO QD on days 22-26, and procarbazine
hydrochloride PO QD on days 22-26. Treatment repeats every 6 weeks for up to 3 courses in
the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 3, 6, 12, 18, and 24

Inclusion Criteria:

- Ability to understand and the willingness to provide written informed consent to

- Adults, 18 years of age or older; date of birth should be determined based on the
best possible information or source documentation available

- HIV-1 infection, documented by any licensed rapid HIV test or HIV enzyme or
chemiluminescence immunoassay (E/CIA) test kit at any time prior to study entry and
confirmed by a licensed Western blot or a second antibody test by a method other than
the initial rapid HIV and/or E/CIA, or confirmed by HIV-1 antigen or plasma HIV-1
ribonucleic acid (RNA) viral load > 1,000 copies/mL

- NOTE: the term "licensed" refers to a United States (U.S.) Food and Drug
Administration (FDA)-approved kit or for sites located in countries other than
the United States, a kit that has been certified or licensed by an oversight
body within that country and validated internally

- WHO (World Health Organization) and CDC (Centers for Disease Control and
Prevention) guidelines mandate that confirmation of the initial test result must
use a test that is different from the one used for the initial assessment; a
reactive initial rapid test should be confirmed by either another type of rapid
assay or an E/CIA that is based on a different antigen preparation and/or
different test principle (e.g., indirect versus competitive), or a Western blot
or a plasma HIV-1 RNA viral load

- Biopsy-proven, measurable or assessable systemic NHL that has been confirmed by an
AIDS Malignancy Clinical Trial Consortium (AMC)-approved site pathologist; if a hard
copy of the pathology report is unavailable at the time of enrollment, a verbal
report by the pathologist confirming the diagnosis must be documented in the medical

- Pathology slides from tumor tissue obtained by surgical excision or core biopsy must
be reviewed by the designated site pathologist, or backup pathologist, prior to study
entry; confirmation of the diagnosis must be documented by the AMC-approved
pathologist prior to study entry; please reference the AMC-068 Manual of Procedures
(MOP) for further instructions on documenting the diagnosis; the site pathologist for
NHL must be approved through the AMC's external quality assessment (EQA) process

- Participants must have fifteen blank(unstained) slides or a diagnostic tissue block
must be available for central pathology review by the AMC Core Pathology Laboratory

- Eastern Cooperative Oncology Group (ECOG) performance status of 0-3

- Participants must have an estimated life expectancy of > 6 weeks

- White blood cells (WBC) >= 3,000 cells/uL (3.0 x 10^9 L) or

- Absolute granulocytes >= 1500 cells/uL (1.5 x 10^9 L)

- Platelets >= 100,000 cells/uL (75 x 10^9 L)

- Hemoglobin > 8 g/dL (5.0 mmol/L)

- Patients may enroll with lower hematologic values, if bone marrow involvement is
documented; in this case, patients should be transfused to hemoglobin > 8 g/dL

- Serum creatinine < 3.0 mg/dL (265.2 umol/L)

- Total bilirubin =< 1.5 institutional upper limit of normal (ULN), unless elevated
secondary to lymphomatous involvement of liver or biliary system, or due to other HIV
medications (e.g., indinavir, tenofovir, or atazanavir); if secondary to lymphomatous
involvement, an initial upper limit of total bilirubin 5 mg/dL (85.5 uM/L) should be
utilized - for direct bilirubin > 1.2 mg/dL (20.5 uM/L)

- Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 2.5 institutional
ULN (unless elevated secondary to lymphomatous involvement of the liver)

- Participants must have a lumbar puncture with negative cerebral spinal fluid cytology
within 6 weeks prior to enrollment; participants must be without evidence for central
nervous system (CNS) lymphoma on neurological exam and have no radiographic evidence
(if radiographic studies are done) of CNS lymphoma (inclusive of parenchymal,
vitreal, or leptomeningeal involvement)

- Participants must not have had any prior chemotherapy or radiation therapy and no
more than 10 days of corticosteroids in the preceding 30 days prior to enrollment

- All participants must be prescribed combination antiretroviral therapy with the goal
of virological suppression using an acceptable regimen that adheres to national
guidelines for treatment of HIV infection; non-suppressed, treatment experienced
patients, defined as patients with a viral load > 400 copies/mL who have been on
antiretroviral therapy for more than 4 months can be enrolled if an alternative
antiretroviral therapy (ART) regimen is available that includes at least two ART
drugs that, in the opinion of the site investigator, are expected to have activity
based on genotypic testing (if available) and treatment history; patients are not
allowed to receive zidovudine (azidothymidine [AZT]) as part of concurrent
chemotherapy and ART regimen, since it is myelosuppressive; zidovudine may be
discontinued and substituted as clinically indicated prior to or at the time of

- Participants of childbearing potential, defined as a sexually mature woman who: 1)
has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been
naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at
any time in the preceding 24 consecutive months), must have a pregnancy test within 7
days prior to enrollment and agree to use an effective form of contraception (e.g.,
barrier contraception, highly effective hormonal contraception)

- Participants are allowed to have an active infection(s) for which they are receiving
drug treatment provided the clinical status is judged to be stable and survival is
estimated to be at least 6 weeks

- Participants must, in the opinion of the investigatory, be capable of complying with
the protocol

- Participants must be able to take oral medications

- Participants must have a CD4 count performed within 30 days of enrollment

Exclusion Criteria:

- Inability to provide informed consent

- A medical or psychiatric illness that precludes ability to give informed consent or
is likely to interfere with the ability to comply with the protocol stipulations

- Participants with circumstances that will not permit completion of the study or
required follow-up; for instance, if travel to and from treatment site is an issue

- Pregnant or breastfeeding

- Inability to swallow oral medications

Type of Study:


Study Design:

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Overall survival

Outcome Description:

The log-rank test will be used to compare the two treatment arms with respect to overall survival. The one-sided 0.20 significance level will be used for this comparison. Proportional hazards models will be used to evaluate the association between covariates (e.g., CD4 count and HIV viral load) and overall survival.

Outcome Time Frame:

Up to 24 months

Safety Issue:


Principal Investigator

Robert Strother

Investigator Role:

Principal Investigator

Investigator Affiliation:

AIDS Associated Malignancies Clinical Trials Consortium


United States: Data and Safety Monitoring Board

Study ID:




Start Date:

June 2013

Completion Date:

Related Keywords:

  • AIDS-related Diffuse Large Cell Lymphoma
  • AIDS-related Diffuse Mixed Cell Lymphoma
  • AIDS-related Diffuse Small Cleaved Cell Lymphoma
  • AIDS-related Immunoblastic Large Cell Lymphoma
  • AIDS-related Lymphoblastic Lymphoma
  • AIDS-related Peripheral/Systemic Lymphoma
  • AIDS-related Small Noncleaved Cell Lymphoma
  • Stage III AIDS-related Lymphoma
  • Stage IV AIDS-related Lymphoma
  • Acquired Immunodeficiency Syndrome
  • HIV Infections
  • Lymphoma
  • Lymphoma, Large B-Cell, Diffuse
  • Lymphoma, Non-Hodgkin
  • Lymphoma, Large-Cell, Immunoblastic
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma
  • Lymphoma, AIDS-Related