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CompletedNCT01352117REACT-KSUpdated Nov 14, 2019Results posted

Antiretroviral Therapy (ART) Alone or With Delayed Chemo Versus ART With Immediate Chemo for Limited AIDS-related Kaposi's Sarcoma

A Phase 3 interventional study of efavirenz/emtricitabine/tenofovir disoproxil fumarate and etoposide in HIV-1 Infection and Kaposi's Sarcoma, sponsored by Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections. Completed at 8 sites in 6 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2019-11-14.

Sponsored by Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections · Phase 3, Interventional, and Treatment

Phase
Phase 3
Study type
Interventional
Enrollment
192
Allocation
Randomized
Ages
18 Years and older
Sex
All
01

Study summary

AIDS-related Kaposi's sarcoma (AIDS-KS) occurs in persons with HIV infection who are also infected with the Kaposi's sarcoma herpesvirus (KSHV). Several chemotherapy (anti-cancer) drugs work well in treating KS, but there is no treatment that cures KSHV infection. One chemotherapy drug called etoposide (VePesid®, ET) has caused KS tumors to get smaller in some people.

Antiretroviral therapy (anti-HIV drugs or ART) is a group of medicines taken together to treat HIV infection. These medicines help to stop HIV from growing in the body. When this happens, the immune system, which fights infection and some cancers like KS, gets stronger. For some people, limited stage KS often improves or stays the same when they take ART. However, in some people KS continues to get worse when taking ART. These people may need chemotherapy at a later date.

This study was done to find out if taking ART with immediate etoposide (ET) is better than taking ART alone or ART with delayed ET to treat limited stage KS. The study also tried to better understand KSHV and to see what kind of side effects are caused by ART and ET and how safe ART and ET are.

Read the detailed description

The study consisted of three steps. At the study Step 1 entry, the participants were randomized (1:1) to receive ART alone (Arm A) or ART with immediate ET (Arm B). Study participants in Arm A who experienced KS progression that was confirmed by the Independent Endpoint Review Committee (IERC) could receive etoposide (ET) in addition to ART by entering Step 2 between study weeks 8 and 80. The target sample size was 468, 234 per arm. Randomization was stratified by:

  1. Screening CD4 cell count (\<200 or ≥200 cells/mm\^3) and
  2. ART history (naïve or experienced).

The duration of Step 1 or Step 1 and 2 combined was 96 weeks. After 96 weeks on study, participants who received ET (Arm B participants and Arm A participants who entered Step 2) entered Step 3 for a total of 144 weeks of safety follow-up.

Step 1 visits occurred at screening, entry and weeks 2, 4, 6, 8, 10, 12, 14, 16, 20, 24, 32, 40, 48, 60, 72, 84 and 96 from study entry. Step 2 visits were scheduled at entry and weeks 2, 4, 6, 8, 10, 12, 14, 16, 20, 24, 32, 40, 48, 60, 72, 84 from Step 2 entry until up to 96 weeks on study. The key evaluations included physical examination, clinical assessments, KS exam, CD4 cell count, HIV viral load, hematology, chemistry and pregnancy testing (for women of reproductive potential). Plasma, serum, peripheral blood mononuclear cells (PBMCs), KS tumor punch biopsy were be stored for use in future analyses. Participants also completed ET and ART adherence evaluations and quality of life questionnaires. Step 3 visits were scheduled every 24 weeks and were limited to safety evaluations including targeted physical exam, clinical assessments and hematology.

Study accrual terminated early, based on the Data and Safety Monitoring Board (DSMB) recommendation in March 2016. The participants in Steps 1 and 2 at that time were arranged to enter either Step 3 for safety follow-up after ET or, if they did not receive ET, to be taken off study.

02

Conditions studied

  • HIV-1 Infection
  • Kaposi's Sarcoma
03

In context

Sarcoma, Kaposi

162 studies on the registry are indexed under Sarcoma, Kaposi; 29 are open to participants now.

This study's enrollment of 192 is above the median of 32 across 114 interventional studies indexed under Sarcoma, Kaposi.

Browse Sarcoma, Kaposi studies →

Lead sponsor

Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections is the lead sponsor of 70 studies on the registry; 3 are open to participants now.

Of its 7 completed or terminated interventional studies of FDA-regulated products, 6 (86%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Eligibility criteria

Step 1: Inclusion Criteria

  1. HIV-1 infection.
  2. Biopsy diagnostic of KS at any time prior to study entry.

  3. Limited stage KS defined as stage T0 and some presentations of stage T1. Stage T0 was confined to skin and/or lymph nodes and/or minimal oral disease defined as non-nodular KS confined to the palate. The following presentations of stage T1 KS were also eligible at the discretion of the site investigator:

    • Tumor-associated edema limited to the area(s) of KS without significant functional impairment.
    • Oral KS that consists of flat (non-nodular and non-ulcerating) lesions confined to the soft palate, hard palate, gums, and buccal mucosa.
    • Asymptomatic gastrointestinal KS (i.e., no unexplained abdominal pain or gastrointestinal bleeding).
  4. A minimum of 5 cutaneous marker lesions
  5. Certain laboratory values obtained within 14 days prior to study entry.
  6. For female participants of reproductive potential, a negative serum or urine pregnancy test performed within 7 days prior to study entry.
  7. All participants must have agreed not to participate in a conception process (e.g., active attempt to become pregnant or to impregnate, donate sperm, in vitro fertilization).
  8. Participants who are participating in sexual activity that could lead to pregnancy must have agreed to use a combination of TWO of the following methods- Condoms (male or female) with or without a spermicidal agent, diaphragm or cervical cap with spermicide, IUD, tubal ligation, and/or hormone-based contraception. For Etoposide, confirmation of lack of reproductive potential was required for all participants. More information on this criterion can be found in the study protocol.
  9. Ability to swallow oral medications.
  10. Karnofsky performance score >= 60 within 30 days prior to entry.
  11. Ability and willingness of participant or legal guardian/representative to provide informed consent.
  12. Peripheral blood CD4+ lymphocyte cell count obtained within 30 days prior to study entry at a DAIDS-approved laboratory.
  13. For treatment-experienced patients, the availability of an ART regimen that includes at least two ART drugs that in the opinion of the site investigator are expected to have activity based on historical genotypic testing (if available) and treatment history.
  14. For participants who were to receive ART other than EFV/TDF/FTC, the availability of those ART components.

Step 2: Inclusion Criteria

  1. KS progression compared to study entry or best response with ART alone while on Step 1, between weeks 8 and 80.
  2. Need for ET for treatment of KS progression, in the opinion of the site investigator, after confirmation of KS progression by the IERC.
  3. Willingness to receive ET for treatment of KS progression.
  4. For female participants of reproductive potential, a negative serum or urine pregnancy test performed within 7 days prior to initiating ET.
  5. Karnofsky Performance Score >= 50.
  6. Certain laboratory values obtained within 14 days prior to Step 2 entry.
  7. Ability to swallow oral medications.
  8. All participants must have agreed not to participate in a conception process (e.g., active attempt to become pregnant or to impregnate, donate sperm, in vitro fertilization).
  9. Participants who are participating in sexual activity that could lead to pregnancy must have agreed to use a combination of TWO of the following methods- Condoms (male or female) with or without a spermicidal agent, diaphragm or cervical cap with spermicide, IUD, tubal ligation, hormone-based contraception. For Etoposide, confirmation of lack of reproductive potential was required for all participants. More information on this criterion can be found in the study protocol.

Step 3: Inclusion Criteria

  1. Received at least one dose of ET (Arm B participants and Arm A participants who entered Step 2)

Step 1: Exclusion Criteria

  1. Any manifestation of KS which, in the opinion of the site investigator, requires immediate chemotherapy.
  2. More than 14 days of ART after onset of KS within 6 months prior to study entry.
  3. Biopsy proven KS during previous ART.
  4. Breastfeeding.
  5. Allergy/sensitivity to any study drug or its formulations.
  6. Any prior systemic anti-neoplastic treatment for KS (including chemotherapy, biological therapy, immunotherapy or investigational therapy).
  7. Any prior local treatment of cutaneous marker lesions unless there was evidence of a clear-cut progression of the lesion.
  8. Receipt of any investigational therapy within 30 days prior to study entry.
  9. Current or anticipated receipt of any of the prohibited medications indicated in the study protocol.
  10. In the opinion of the site investigator, any psychological or social condition, or addictive disorder that would have precluded compliance with the protocol.
  11. Chronic, acute, or recurrent infections that were serious, in the opinion of the site investigator, for which the participant had not completed at least 14 days of therapy prior to study entry and/or was not clinically stable.

Step 2: Exclusion Criteria

  1. Chronic, acute, or recurrent infections that were serious, in the opinion of the site investigator, for which the participant had not completed at least 14 days of therapy prior to initiating ET and/or was not clinically stable.
  2. Current or anticipated receipt of any of the prohibited medications indicated in the study protocol.
  3. Breastfeeding.

There are no exclusion criteria for Step 3.

05

Study design

Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
192 participants (actual)

Study arms

  • Active comparator
    Arm A: ART alone or with delayed ET

    Participants were prescribed ART (co-formulated efavirenz/emtricitabine/tenofovir disoproxil fumarate, EFV/FTC/TDF) for 96 weeks. Arm A participants who experienced KS progression on ART alone could receive ET in addition to EFV/FTC/TDF in Step 2 of the study.

    Drug: efavirenz/emtricitabine/tenofovir disoproxil fumarate · Drug: etoposide

  • Experimental
    Arm B: ART with immediate ET

    Participants were prescribed ART (co-formulated efavirenz/emtricitabine/tenofovir disoproxil fumarate, EFV/FTC/TDF) for 96 weeks with immediate ET for up to 16 weeks.

    Drug: efavirenz/emtricitabine/tenofovir disoproxil fumarate · Drug: etoposide

Interventions

  • Drugefavirenz/emtricitabine/tenofovir disoproxil fumarate

    600 mg efavirenz/200 mg emtricitabine/300 mg tenofovir disoproxil fumarate taken orally at night

    Also known as: Atripla®, EFV/FTC/TDF

  • Drugetoposide

    50 mg taken orally daily from days 1-7 of each 2-week cycle. For participants without PR or CR after two cycles of therapy and no toxicity greater than Grade 2, the dose of ET was escalated to 100 mg/day orally, days 1-7, every 2 weeks. A cycle could be delayed for a maximum of 14 days. ET could not be initiated prior to 7 days after the last dose in previous cycle. ET could be administered up to a maximum of eight cycles (2 cycles during dose titration and 6 cycles at maximum dose). Participants who could not tolerate escalation of the ET dose to 100 mg/day were treated for a maximum of six cycles.

    Also known as: VePesid®, ET

06

What researchers measure

Primary outcomes

  1. Kaposi Sarcoma (KS) Status at Week 48 Compared to Study Entry

    KS status is a composite, categorical outcome, ordered from worst to best as E1 (Failure: KS progression (PD), initiation of an alternate KS treatment, or no follow-up at Week 48 including death and missed visit), E2 (Stable: in follow-up at Week 48 with no KS PD nor response and without initiation of an alternate KS treatment) and E3 (Response: in follow-up at Week 48, with KS partial or complete response (PR or CR) and without initiation of an alternate KS treatment). Alternate KS treatment was defined as chemotherapy agent other than ET or other treatment triggered by worsening KS. KS outcome status (PR, stable, PR, CR) compared to study entry was evaluated at Week 48 based on clinical assessment of KS cutaneous lesions (count, character and marker lesion area), oral KS, visceral KS and tumor-associated edema and as described in the publications (Krown et al 1989, Cianfrocca et al 2002). Data on initiation of alternate KS treatment, loss to follow-up and dea

    Time frame: Entry through Week 48.

Secondary outcomes

  1. KS Progressive Disease at Week 48 Compared to Study Entry

    KS progressive disease (PD) compared to study entry based on clinical assessment of KS cutaneous lesions (count, character and marker lesion area), oral KS, visceral KS and tumor-associated edema and as described in the publications (Krown et al 1989, Cianfrocca et al 2002).

    Time frame: Entry and Week 48

  2. KS Partial Response at Week 48 Compared to Study Entry

    KS partial response (PR) compared to study entry based on clinical assessment of KS cutaneous lesions (count, character and marker lesion area), oral KS, visceral KS and tumor-associated edema and as described in the publications (Krown et al 1989, Cianfrocca et al 2002).

    Time frame: Entry and Week 48

  3. KS Complete Response at Week 48 Compared to Study Entry

    KS complete response (CR) compared to study entry based on clinical assessment of KS cutaneous lesions (count, character and marker lesion area), oral KS, visceral KS and tumor-associated edema and as described in the publications (Krown et al 1989, Cianfrocca et al 2002).

    Time frame: Entry and Week 48

  4. KS Partial or Complete Response at Week 48 Compared to Study Entry

    KS partial response (PR) or complete response (CR) compared to study entry based on clinical assessment of KS cutaneous lesions (count, character and marker lesion area), oral KS, visceral KS and tumor-associated edema and as described in the publications (Krown et al 1989, Cianfrocca et al 2002).

    Time frame: Entry and Week 48

  5. Premature Study Discontinuation by Week 48

    Premature study discontinuation by Week 48 due to any reason, including death.

    Time frame: Entry through Week 48

  6. Kaposi Sarcoma (KS) Status at Week 96 Compared to Study Entry

    KS status is a composite, categorical outcome, ordered from worst to best as E1 (Failure: KS PD, initiation of an alternate KS treatment, or no follow-up at Week 96 including death and missed visit), E2 (Stable: in follow-up at Week 96 with no KS progression nor response and without initiation of an alternate KS treatment) and E3 (Response: in follow-up at Week 96, with KS PR or CR and without initiation of an alternate KS treatment). Alternate KS treatment was defined as chemotherapy agent other than ET or other treatment triggered by worsening KS. KS outcome status (PD, stable, PR or CR) compared to study entry was evaluated at Week 96 based on clinical assessment of KS cutaneous lesions (count, character and marker lesion area), oral KS, visceral KS and tumor-associated edema and as described in the publications (Krown et al 1989, Cianfrocca et al 2002). Data on initiation of alternate KS treatment, loss to follow-up and deaths are from entry through Week 96.

    Time frame: Entry through Week 96.

  7. KS Progressive Disease at Week 96 Compared to Study Entry

    KS progressive disease (PD) compared to study entry based on clinical assessment of KS cutaneous lesions (count, character and marker lesion area), oral KS, visceral KS and tumor-associated edema and as described in the publications (Krown et al 1989, Cianfrocca et al 2002).

    Time frame: Entry and Week 96

  8. KS Partial Response at Week 96 Compared to Study Entry

    KS partial response (PR) compared to study entry based on clinical assessment of KS cutaneous lesions (count, character and marker lesion area), oral KS, visceral KS and tumor-associated edema and as described in the publications (Krown et al 1989, Cianfrocca et al 2002).

    Time frame: Entry and Week 96

  9. KS Complete Response at Week 96 Compared to Study Entry

    KS complete response (CR) compared to study entry based on clinical assessment of KS cutaneous lesions (count, character and marker lesion area), oral KS, visceral KS and tumor-associated edema and as described in the publications (Krown et al 1989, Cianfrocca et al 2002).

    Time frame: Entry and Week 96

  10. KS Partial or Complete Response at Week 96 Compared to Study Entry

    KS partial response (PR) or complete response (CR) compared to study entry based on clinical assessment of KS cutaneous lesions (count, character and marker lesion area), oral KS, visceral KS and tumor-associated edema and as described in the publications (Krown et al 1989, Cianfrocca et al 2002).

    Time frame: Entry and Week 96

  11. Premature Study Discontinuation by Week 96

    Premature study discontinuation by Week 96 due to any reason, including death.

    Time frame: Entry through Week 96

  12. Cumulative Incidence of Initial KS Progressive Disease by Week 96

    KS progressive disease (PD) compared to study entry or best response based on clinical assessment of KS cutaneous lesions (count, character and marker lesion area), oral KS, visceral KS and tumor-associated edema and as described in the publications (Krown et al 1989, Cianfrocca et al 2002). Cumulative incidence was estimated with death and initiation of alternate KS treatment as competing risks. Time at risk was censored at the end of Step 1 (Week 96 or premature study discontinuation) or on the date when the DSMB's recommendation to close the study became public, whichever occurred earlier.

    Time frame: From entry through 96 weeks

  13. Cumulative Incidence of Initial KS Partial or Complete Response by Week 96

    KS partial response (PR) or complete response (CR) compared to study entry based on clinical assessment of KS cutaneous lesions (count, character and marker lesion area), oral KS, visceral KS and tumor-associated edema and as described in the publications (Krown et al 1989, Cianfrocca et al 2002). Cumulative incidence was estimated with death and initiation of delayed KS treatment (alternate KS treatment or delayed ET in Arm A) as competing risks. Time at risk was censored at the end of Step 1 (Week 96 or premature study discontinuation) or on the date when the DSMB's recommendation to close the study became public, whichever occurred earlier.

    Time frame: From entry through 96 weeks

  14. Cumulative Incidence of Initial KS Partial Response by Week 96

    KS partial response (PR) compared to study entry based on clinical assessment of KS cutaneous lesions (count, character and marker lesion area), oral KS, visceral KS and tumor-associated edema and as described in the publications (Krown et al 1989, Cianfrocca et al 2002). This was initially part of the outcome specified in the study protocol as "PR and CR combined and separately" to address the secondary objective on the KS response. Due to the extremely limited number of participants with KS complete response, the Statistical Analysis Plan was updated, and the Final Analysis was conducted only on the combined KS response. The outcome on PR separately was withdrawn.

    Time frame: From study treatment initiation to 96 weeks

  15. Cumulative Incidence of Initial KS Complete Response by Week 96

    KS complete response (CR) compared to study entry based on clinical evaluation of KS cutaneous lesions (count, character and marker lesion area), oral KS, visceral KS and tumor-associated edema and as described in the publications (Krown et al 1989, Cianfrocca et al 2002). This was initially part of the outcome specified in the study protocol as "PR and CR combined and separately" to address the secondary objective on the KS response. Due to the extremely limited number of participants with KS CR, the Statistical Analysis Plan was updated, and the Final Analysis was conducted only on the combined KS response. The outcome on CR separately was withdrawn.

    Time frame: From study treatment initiation to 96 weeks

  16. Number of Participants With Grade 3 or Higher Adverse Events

    Number of participants who experienced an AE (sign/symptom or laboratory abnormality) of Grade 3 or higher. The AEs were graded by the clinicians according to the Division of AIDS (DAIDS) AE Grading Table (see reference in the Protocol Section) as follows: Grade 1=Mild, Grade 2=Moderate, Grade 3=Severe, Grade 4=Potentially Life-Threatening.

    Time frame: From study treatment dispensation through up to Week 96, until long-term follow-up began in Step 3 or until study discontinuation.

  17. Cumulative Incidence of KS-IRIS

    KS-IRIS was defined as KS progressive disease that occurs within 12 weeks of initiation of ART that is associated with an increase in peripheral blood CD4+ lymphocyte cell count of at least 50 cells/mm\^3 above the study screening value and/or a decrease in the HIV RNA level by at least 0.5 log10 below the study entry value prior to, or at the time of, documented KS progressive disease. Cumulative incidence was estimated with death and initiation of alternate KS treatment as competing risks. Time at risk was censored (1) when lost to follow-up, (2) at the study visit following Week 12 or (3) on the date when the DSMB's recommendation to close the study became public, whichever occurred earlier. Time of KS-IRIS was defined as the time of the initial KS progressive disease.

    Time frame: From study entry to Week 12

  18. Percentage of Participants With Etoposide Dose Modification

    Etoposide (ET) was administered for a maximum of 8 cycles (16 weeks) from study entry (Arm B) or from Step 2 entry (Arm A). Dose modifications were reported as temporarily held, resumed at a different dose, deferred, prematurely discontinued and underdosed. The percentage of participants who experienced each dose modification is provided in the data table below. The categories are not mutually exclusive. A participant may have experienced multiple dose modifications and may be counted in more than one category. Each participant is counted at most once within category.

    Time frame: From ET dispensation to ET discontinuation (total duration of ET was up to 16 weeks)

  19. Percentage of Participants With HIV-1 RNA Suppression

    HIV-1 RNA suppression was defined as plasma HIV-1 RNA \<400 copies/mL. Only Arm A participants could enter Step 2 to initiate delayed ET.

    Time frame: Entry and Weeks 12, 24, 32, 48, 72, 96; Step 2 entry and Weeks 12, 24, 32, 48 and 72.

  20. Percentage of Participants With ARV Dose Modification

    ARV dose modifications were reported as temporarily held, prematurely discontinued and increased. The percentage of participants who experienced each dose modification is provided in the data table below. The categories are not mutually exclusive. A participant may have experienced multiple dose modifications and may be counted in more than one category. Each participant is counted at most once within category.

    Time frame: From treatment dispensation to Week 96

  21. Change in log10 HIV-1 Plasma Viral Load From Entry

    Absolute change in log10 HIV-1 RNA from entry at study visits calculated as value at a given time point minus value at entry. This outcome was initially specified in the study protocol. However, at the first post-entry visit, most participants had unquantifiable HIV-1 RNA levels. It would be misleading to calculate change from entry to HIV RNA-1 levels that could not be quantified. Therefore, the data collected did not support the outcome and the analytic method initially proposed in the study protocol, and this outcome measure could not be analyzed. The SAP updated the HIV-1 RNA outcome measure to HIV-1 RNA suppression at study visits (please refer to the secondary outcome measure #20).

    Time frame: Entry and Weeks 12, 24, 32, 48, 72, 96; Step 2 entry and Weeks 12, 24, 32, 48 and 72.

  22. Change in Peripheral Blood CD4+ Lymphocyte Cell Count

    Absolute change in CD4+ cell count was calculated as value at a given visit minus the value at study screening in Step 1, and as value at a given visit minus Step 2 entry in Step 2. Only participants in Arm A could enter Step 2 to initiate delayed ET.

    Time frame: Screening and Weeks 12, 24, 32, 48, 72, 96; Step 2 entry and Weeks 12, 24, 32, 48 and 72.

  23. Cumulative Incidence of KS Progressive Disease After Initiation of Delayed Etoposide in Arm A

    KS progressive disease (PD) compared to Step 2 entry (prior to initiation of delayed ET) or Step 2 best response based on clinical assessment of KS cutaneous lesions (count, character and marker lesion area), oral KS, visceral KS and tumor-associated edema and as described in the publications (Krown et al 1989, Cianfrocca et al 2002). Cumulative incidence was estimated with death and initiation of alternate KS treatment as competing risks. Time at risk was censored at the end of Step 2 (at up to 84 weeks or premature study discontinuation) or on the date when the DSMB's recommendation to close the study became public, whichever occurred earlier.

    Time frame: From initiation of etoposide (Step 2 entry) to up to 84 weeks (end of Step 2)

  24. Cumulative Incidence of KS Response After Initiation of Delayed Etoposide in Arm A

    KS response, partial or complete (PR or CR) compared to Step 2 entry (prior to initiation of delayed ET) based on clinical assessment of KS cutaneous lesions (count, character and marker lesion area), oral KS, visceral KS and tumor-associated edema and as described in the publications (Krown et al 1989, Cianfrocca et al 2002). Cumulative incidence was estimated with death and initiation of alternate KS treatment as competing risks. Time at risk was censored at the end of Step 2 (at up to 84 weeks or premature study discontinuation) or on the date when the DSMB's recommendation to close the study became public, whichever occurred earlier.

    Time frame: From initiation of etoposide (Step 2 entry) to up to 84 weeks (end of Step 2)

07

Results

Posted Jul 31, 2017

Participant flow

Participants were recruited from November 2011 to February 2016 at 10 sites in Africa and South America.

Participant flow — Overall Study
MilestoneArm A: ART Alone or With Delayed ETArm B: ART With Immediate ET
Started9696
Entered step 2 to initiate delayed et320
Study week 48 data potential8083
Study week 96 data potential5861
Completed7572
Not completed2124
Withdrew: Death1516
Withdrew: Withdrawal by subject10
Withdrew: Lost to follow-up27
Withdrew: Non-adherent to study requirements11
Withdrew: Did not initiate study treatment10
Withdrew: Ineligible (no ks diagnosis)10

Outcome measures

PrimaryKaposi Sarcoma (KS) Status at Week 48 Compared to Study Entry

KS status is a composite, categorical outcome, ordered from worst to best as E1 (Failure: KS progression (PD), initiation of an alternate KS treatment, or no follow-up at Week 48 including death and missed visit), E2 (Stable: in follow-up at Week 48 with no KS PD nor response and without initiation of an alternate KS treatment) and E3 (Response: in follow-up at Week 48, with KS partial or complete response (PR or CR) and without initiation of an alternate KS treatment). Alternate KS treatment was defined as chemotherapy agent other than ET or other treatment triggered by worsening KS. KS outcome status (PR, stable, PR, CR) compared to study entry was evaluated at Week 48 based on clinical assessment of KS cutaneous lesions (count, character and marker lesion area), oral KS, visceral KS and tumor-associated edema and as described in the publications (Krown et al 1989, Cianfrocca et al 2002). Data on initiation of alternate KS treatment, loss to follow-up and dea

Time frame:
Entry through Week 48.
Reported as:
Count of participants · Participants
Kaposi Sarcoma (KS) Status at Week 48 Compared to Study Entry
ParticipantsArm A: ART Alone or With Delayed ETArm B: ART With Immediate ET
E1 (Failure)4347
E2 (Stable)139
E3 (Response)2427
Statistical analysis
  • Arm A: ART Alone or With Delayed ET vs Arm B: ART With Immediate ET · Wilcoxon (Mann-Whitney) · p = 0.911 (The critical value for the final analysis was adjusted for the three interim analyses conducted for the Data and Safety Monitoring Board (DSMB) review using the Haybittle-Peto guidelines, at the p-value cutoff of 0.0487.)Stratified Wilcoxon-Mann-Whitney test (asymptotic method) known as van Elteren test, stratification by screening CD4 (\<200 vs. \>=200 cells/mm\^3).
SecondaryKS Progressive Disease at Week 48 Compared to Study Entry

KS progressive disease (PD) compared to study entry based on clinical assessment of KS cutaneous lesions (count, character and marker lesion area), oral KS, visceral KS and tumor-associated edema and as described in the publications (Krown et al 1989, Cianfrocca et al 2002).

Time frame:
Entry and Week 48
Reported as:
Count of participants · Participants
KS Progressive Disease at Week 48 Compared to Study Entry
ParticipantsArm A: ART Alone or With Delayed ETArm B: ART With Immediate ET
KS PD at Week 48217
No KS PD at Week 483736
SecondaryKS Partial Response at Week 48 Compared to Study Entry

KS partial response (PR) compared to study entry based on clinical assessment of KS cutaneous lesions (count, character and marker lesion area), oral KS, visceral KS and tumor-associated edema and as described in the publications (Krown et al 1989, Cianfrocca et al 2002).

Time frame:
Entry and Week 48
Reported as:
Count of participants · Participants
KS Partial Response at Week 48 Compared to Study Entry
ParticipantsArm A: ART Alone or With Delayed ETArm B: ART With Immediate ET
KS PR at Week 482123
No KS PR at Week 483720
SecondaryKS Complete Response at Week 48 Compared to Study Entry

KS complete response (CR) compared to study entry based on clinical assessment of KS cutaneous lesions (count, character and marker lesion area), oral KS, visceral KS and tumor-associated edema and as described in the publications (Krown et al 1989, Cianfrocca et al 2002).

Time frame:
Entry and Week 48
Reported as:
Count of participants · Participants
KS Complete Response at Week 48 Compared to Study Entry
ParticipantsArm A: ART Alone or With Delayed ETArm B: ART With Immediate ET
KS CR at Week 4834
No KS CR at Week 485539
SecondaryKS Partial or Complete Response at Week 48 Compared to Study Entry

KS partial response (PR) or complete response (CR) compared to study entry based on clinical assessment of KS cutaneous lesions (count, character and marker lesion area), oral KS, visceral KS and tumor-associated edema and as described in the publications (Krown et al 1989, Cianfrocca et al 2002).

Time frame:
Entry and Week 48
Reported as:
Count of participants · Participants
KS Partial or Complete Response at Week 48 Compared to Study Entry
ParticipantsArm A: ART Alone or With Delayed ETArm B: ART With Immediate ET
Week 48: KS PR or CR2427
Week 48: no KS PR or CR3416
SecondaryPremature Study Discontinuation by Week 48

Premature study discontinuation by Week 48 due to any reason, including death.

Time frame:
Entry through Week 48
Reported as:
Count of participants · Participants
Premature Study Discontinuation by Week 48
ParticipantsArm A: ART Alone or With Delayed ETArm B: ART With Immediate ET
Premature study discontinuation by Week 481311
No premature study discontinuation by Week 486772
SecondaryKaposi Sarcoma (KS) Status at Week 96 Compared to Study Entry

KS status is a composite, categorical outcome, ordered from worst to best as E1 (Failure: KS PD, initiation of an alternate KS treatment, or no follow-up at Week 96 including death and missed visit), E2 (Stable: in follow-up at Week 96 with no KS progression nor response and without initiation of an alternate KS treatment) and E3 (Response: in follow-up at Week 96, with KS PR or CR and without initiation of an alternate KS treatment). Alternate KS treatment was defined as chemotherapy agent other than ET or other treatment triggered by worsening KS. KS outcome status (PD, stable, PR or CR) compared to study entry was evaluated at Week 96 based on clinical assessment of KS cutaneous lesions (count, character and marker lesion area), oral KS, visceral KS and tumor-associated edema and as described in the publications (Krown et al 1989, Cianfrocca et al 2002). Data on initiation of alternate KS treatment, loss to follow-up and deaths are from entry through Week 96.

Time frame:
Entry through Week 96.
Reported as:
Count of participants · Participants
Kaposi Sarcoma (KS) Status at Week 96 Compared to Study Entry
ParticipantsArm A: ART Alone or With Delayed ETArm B: ART With Immediate ET
E1 (Failure)3333
E2 (Stable)40
E3 (Response)2128
SecondaryKS Progressive Disease at Week 96 Compared to Study Entry

KS progressive disease (PD) compared to study entry based on clinical assessment of KS cutaneous lesions (count, character and marker lesion area), oral KS, visceral KS and tumor-associated edema and as described in the publications (Krown et al 1989, Cianfrocca et al 2002).

Time frame:
Entry and Week 96
Reported as:
Count of participants · Participants
KS Progressive Disease at Week 96 Compared to Study Entry
ParticipantsArm A: ART Alone or With Delayed ETArm B: ART With Immediate ET
KS PD at Week 96102
No KS PD at Week 962528
SecondaryKS Partial Response at Week 96 Compared to Study Entry

KS partial response (PR) compared to study entry based on clinical assessment of KS cutaneous lesions (count, character and marker lesion area), oral KS, visceral KS and tumor-associated edema and as described in the publications (Krown et al 1989, Cianfrocca et al 2002).

Time frame:
Entry and Week 96
Reported as:
Count of participants · Participants
KS Partial Response at Week 96 Compared to Study Entry
ParticipantsArm A: ART Alone or With Delayed ETArm B: ART With Immediate ET
KS PR at Week 961924
No KS PR at Week 96166
SecondaryKS Complete Response at Week 96 Compared to Study Entry

KS complete response (CR) compared to study entry based on clinical assessment of KS cutaneous lesions (count, character and marker lesion area), oral KS, visceral KS and tumor-associated edema and as described in the publications (Krown et al 1989, Cianfrocca et al 2002).

Time frame:
Entry and Week 96
Reported as:
Count of participants · Participants
KS Complete Response at Week 96 Compared to Study Entry
ParticipantsArm A: ART Alone or With Delayed ETArm B: ART With Immediate ET
KS CR at Week 9624
No KS CR at Week 963326
SecondaryKS Partial or Complete Response at Week 96 Compared to Study Entry

KS partial response (PR) or complete response (CR) compared to study entry based on clinical assessment of KS cutaneous lesions (count, character and marker lesion area), oral KS, visceral KS and tumor-associated edema and as described in the publications (Krown et al 1989, Cianfrocca et al 2002).

Time frame:
Entry and Week 96
Reported as:
Count of participants · Participants
KS Partial or Complete Response at Week 96 Compared to Study Entry
ParticipantsArm A: ART Alone or With Delayed ETArm B: ART With Immediate ET
KS PR or CR at Week 962128
No KS PR or CR at Week 96142
SecondaryPremature Study Discontinuation by Week 96

Premature study discontinuation by Week 96 due to any reason, including death.

Time frame:
Entry through Week 96
Reported as:
Count of participants · Participants
Premature Study Discontinuation by Week 96
ParticipantsArm A: ART Alone or With Delayed ETArm B: ART With Immediate ET
Premature study discontinuation by Week 961410
No premature study discontinuation by Week 964451
SecondaryCumulative Incidence of Initial KS Progressive Disease by Week 96

KS progressive disease (PD) compared to study entry or best response based on clinical assessment of KS cutaneous lesions (count, character and marker lesion area), oral KS, visceral KS and tumor-associated edema and as described in the publications (Krown et al 1989, Cianfrocca et al 2002). Cumulative incidence was estimated with death and initiation of alternate KS treatment as competing risks. Time at risk was censored at the end of Step 1 (Week 96 or premature study discontinuation) or on the date when the DSMB's recommendation to close the study became public, whichever occurred earlier.

Time frame:
From entry through 96 weeks
Reported as:
Number · cumulative events per 100 participants
Cumulative Incidence of Initial KS Progressive Disease by Week 96
cumulative events per 100 participantsArm A: ART Alone Period (Step 1)Arm B: ART With Immediate ET
Cumulative Incidence of Initial KS Progressive Disease by Week 9660.61 (48.98 to 70.38)52.73 (40.17 to 63.82)
SecondaryCumulative Incidence of Initial KS Partial or Complete Response by Week 96

KS partial response (PR) or complete response (CR) compared to study entry based on clinical assessment of KS cutaneous lesions (count, character and marker lesion area), oral KS, visceral KS and tumor-associated edema and as described in the publications (Krown et al 1989, Cianfrocca et al 2002). Cumulative incidence was estimated with death and initiation of delayed KS treatment (alternate KS treatment or delayed ET in Arm A) as competing risks. Time at risk was censored at the end of Step 1 (Week 96 or premature study discontinuation) or on the date when the DSMB's recommendation to close the study became public, whichever occurred earlier.

Time frame:
From entry through 96 weeks
Reported as:
Number · cumulative events per 100 participants
Cumulative Incidence of Initial KS Partial or Complete Response by Week 96
cumulative events per 100 participantsArm A: ART Alone Period (Step 1)Arm B: ART With Immediate ET
Cumulative Incidence of Initial KS Partial or Complete Response by Week 9639.89 (24.88 to 54.48)64.08 (51.78 to 74.01)
SecondaryCumulative Incidence of Initial KS Partial Response by Week 96

KS partial response (PR) compared to study entry based on clinical assessment of KS cutaneous lesions (count, character and marker lesion area), oral KS, visceral KS and tumor-associated edema and as described in the publications (Krown et al 1989, Cianfrocca et al 2002). This was initially part of the outcome specified in the study protocol as "PR and CR combined and separately" to address the secondary objective on the KS response. Due to the extremely limited number of participants with KS complete response, the Statistical Analysis Plan was updated, and the Final Analysis was conducted only on the combined KS response. The outcome on PR separately was withdrawn.

Time frame:
From study treatment initiation to 96 weeks

No measurements were reported for this outcome.

SecondaryCumulative Incidence of Initial KS Complete Response by Week 96

KS complete response (CR) compared to study entry based on clinical evaluation of KS cutaneous lesions (count, character and marker lesion area), oral KS, visceral KS and tumor-associated edema and as described in the publications (Krown et al 1989, Cianfrocca et al 2002). This was initially part of the outcome specified in the study protocol as "PR and CR combined and separately" to address the secondary objective on the KS response. Due to the extremely limited number of participants with KS CR, the Statistical Analysis Plan was updated, and the Final Analysis was conducted only on the combined KS response. The outcome on CR separately was withdrawn.

Time frame:
From study treatment initiation to 96 weeks

No measurements were reported for this outcome.

SecondaryNumber of Participants With Grade 3 or Higher Adverse Events

Number of participants who experienced an AE (sign/symptom or laboratory abnormality) of Grade 3 or higher. The AEs were graded by the clinicians according to the Division of AIDS (DAIDS) AE Grading Table (see reference in the Protocol Section) as follows: Grade 1=Mild, Grade 2=Moderate, Grade 3=Severe, Grade 4=Potentially Life-Threatening.

Time frame:
From study treatment dispensation through up to Week 96, until long-term follow-up began in Step 3 or until study discontinuation.
Reported as:
Count of participants · Participants
Number of Participants With Grade 3 or Higher Adverse Events
ParticipantsArm A: ART Alone or With Delayed ETArm B: ART With Immediate ET
Number of Participants With Grade 3 or Higher Adverse Events4742
SecondaryCumulative Incidence of KS-IRIS

KS-IRIS was defined as KS progressive disease that occurs within 12 weeks of initiation of ART that is associated with an increase in peripheral blood CD4+ lymphocyte cell count of at least 50 cells/mm\^3 above the study screening value and/or a decrease in the HIV RNA level by at least 0.5 log10 below the study entry value prior to, or at the time of, documented KS progressive disease. Cumulative incidence was estimated with death and initiation of alternate KS treatment as competing risks. Time at risk was censored (1) when lost to follow-up, (2) at the study visit following Week 12 or (3) on the date when the DSMB's recommendation to close the study became public, whichever occurred earlier. Time of KS-IRIS was defined as the time of the initial KS progressive disease.

Time frame:
From study entry to Week 12
Reported as:
Number · cumulative events per 100 participants
Cumulative Incidence of KS-IRIS
cumulative events per 100 participantsArm A: ART Alone or With Delayed ETArm B: ART With Immediate ET
Cumulative Incidence of KS-IRIS23.14 (15.03 to 32.29)7.40 (3.24 to 13.85)
SecondaryPercentage of Participants With Etoposide Dose Modification

Etoposide (ET) was administered for a maximum of 8 cycles (16 weeks) from study entry (Arm B) or from Step 2 entry (Arm A). Dose modifications were reported as temporarily held, resumed at a different dose, deferred, prematurely discontinued and underdosed. The percentage of participants who experienced each dose modification is provided in the data table below. The categories are not mutually exclusive. A participant may have experienced multiple dose modifications and may be counted in more than one category. Each participant is counted at most once within category.

Time frame:
From ET dispensation to ET discontinuation (total duration of ET was up to 16 weeks)
Reported as:
Number · percentage of participants
Percentage of Participants With Etoposide Dose Modification
percentage of participantsArm A: ART With Delayed ET (Step 2)Arm B: ART With Immediate ET
Temporarily held05.2
Resumed at a different dose15.69.4
Deferred37.524.0
Discontinued6.310.4
Underdosed01.0
SecondaryPercentage of Participants With HIV-1 RNA Suppression

HIV-1 RNA suppression was defined as plasma HIV-1 RNA \<400 copies/mL. Only Arm A participants could enter Step 2 to initiate delayed ET.

Time frame:
Entry and Weeks 12, 24, 32, 48, 72, 96; Step 2 entry and Weeks 12, 24, 32, 48 and 72.
Reported as:
Number · percentage of participants
Percentage of Participants With HIV-1 RNA Suppression
percentage of participantsArm A: ART Alone or With Delayed ETArm B: ART With Immediate ET
Entry: HIV-1 RNA suppression4.34.2
Week 12: HIV-1 RNA suppression90.390.6
Week 24: HIV-1 RNA suppression94.597.5
Week 32: HIV-1 RNA suppression92.094.7
Week 48: HIV-1 RNA suppression95.398.6
Week 72: HIV-1 RNA suppression91.296.6
Week 96: HIV-1 RNA suppression92.993.8
Step 2 entry: HIV-1 RNA suppression93.3—
Step 2 Week 12: HIV-1 RNA suppression100.0—
Step 2 Week 24: HIV-1 RNA suppression95.8—
Step 2 Week 32: HIV-1 RNA suppression96.0—
Step 2 Week 48: HIV-1 RNA suppression100.0—
Step 2 Week 72: HIV-1 RNA suppression100.0—
SecondaryPercentage of Participants With ARV Dose Modification

ARV dose modifications were reported as temporarily held, prematurely discontinued and increased. The percentage of participants who experienced each dose modification is provided in the data table below. The categories are not mutually exclusive. A participant may have experienced multiple dose modifications and may be counted in more than one category. Each participant is counted at most once within category.

Time frame:
From treatment dispensation to Week 96
Reported as:
Number · percentage of participants
Percentage of Participants With ARV Dose Modification
percentage of participantsArm A: ART Alone or With Delayed ETArm B: ART With Immediate ET
Temporarily held7.411.5
Prematurely discontinued26.621.9
Increased1.10
SecondaryChange in log10 HIV-1 Plasma Viral Load From Entry

Absolute change in log10 HIV-1 RNA from entry at study visits calculated as value at a given time point minus value at entry. This outcome was initially specified in the study protocol. However, at the first post-entry visit, most participants had unquantifiable HIV-1 RNA levels. It would be misleading to calculate change from entry to HIV RNA-1 levels that could not be quantified. Therefore, the data collected did not support the outcome and the analytic method initially proposed in the study protocol, and this outcome measure could not be analyzed. The SAP updated the HIV-1 RNA outcome measure to HIV-1 RNA suppression at study visits (please refer to the secondary outcome measure #20).

Time frame:
Entry and Weeks 12, 24, 32, 48, 72, 96; Step 2 entry and Weeks 12, 24, 32, 48 and 72.

No measurements were reported for this outcome.

SecondaryChange in Peripheral Blood CD4+ Lymphocyte Cell Count

Absolute change in CD4+ cell count was calculated as value at a given visit minus the value at study screening in Step 1, and as value at a given visit minus Step 2 entry in Step 2. Only participants in Arm A could enter Step 2 to initiate delayed ET.

Time frame:
Screening and Weeks 12, 24, 32, 48, 72, 96; Step 2 entry and Weeks 12, 24, 32, 48 and 72.
Reported as:
Median · cells/mm^3
Change in Peripheral Blood CD4+ Lymphocyte Cell Count
cells/mm^3Arm A: ART Alone or With Delayed ETArm B: ART With Immediate ET
Week 12: CD4 change40 (12 to 118)67 (5 to 114)
Week 24: CD4 change57 (3 to 139)121 (47 to 210)
Week 32: CD4 change90 (36 to 157)119 (60 to 216)
Week 48: CD4 change125 (39 to 186)121 (61 to 208)
Week 72: CD4 change143 (66 to 290)125 (66 to 257)
Week 96: CD4 change149 (75 to 265)206 (118 to 290)
Step 2 Week 12: CD4 change-13 (-74 to 83)—
Step 2 Week 24: CD4 change-15 (-35 to 51)—
Step 2 Week 32: CD4 change28 (-7 to 71)—
Step 2 Week 48: CD4 change2 (-108 to 143)—
Step 2 Week 72: CD4 change51 (-97 to 131)—
SecondaryCumulative Incidence of KS Progressive Disease After Initiation of Delayed Etoposide in Arm A

KS progressive disease (PD) compared to Step 2 entry (prior to initiation of delayed ET) or Step 2 best response based on clinical assessment of KS cutaneous lesions (count, character and marker lesion area), oral KS, visceral KS and tumor-associated edema and as described in the publications (Krown et al 1989, Cianfrocca et al 2002). Cumulative incidence was estimated with death and initiation of alternate KS treatment as competing risks. Time at risk was censored at the end of Step 2 (at up to 84 weeks or premature study discontinuation) or on the date when the DSMB's recommendation to close the study became public, whichever occurred earlier.

Time frame:
From initiation of etoposide (Step 2 entry) to up to 84 weeks (end of Step 2)
Reported as:
Number · cumulative events per 100 participants
Cumulative Incidence of KS Progressive Disease After Initiation of Delayed Etoposide in Arm A
cumulative events per 100 participantsArm A: ART With Delayed ET Period (Step 2)
Cumulative Incidence of KS Progressive Disease After Initiation of Delayed Etoposide in Arm A35.78 (17.74 to 54.28)
SecondaryCumulative Incidence of KS Response After Initiation of Delayed Etoposide in Arm A

KS response, partial or complete (PR or CR) compared to Step 2 entry (prior to initiation of delayed ET) based on clinical assessment of KS cutaneous lesions (count, character and marker lesion area), oral KS, visceral KS and tumor-associated edema and as described in the publications (Krown et al 1989, Cianfrocca et al 2002). Cumulative incidence was estimated with death and initiation of alternate KS treatment as competing risks. Time at risk was censored at the end of Step 2 (at up to 84 weeks or premature study discontinuation) or on the date when the DSMB's recommendation to close the study became public, whichever occurred earlier.

Time frame:
From initiation of etoposide (Step 2 entry) to up to 84 weeks (end of Step 2)
Reported as:
Number · cumulative events per 100 participants
Cumulative Incidence of KS Response After Initiation of Delayed Etoposide in Arm A
cumulative events per 100 participantsArm A: ART With Delayed ET Period (Step 2)
Cumulative Incidence of KS Response After Initiation of Delayed Etoposide in Arm A62.57 (31.65 to 82.60)

Adverse events

Collected over From study treatment dispensation to study completion at up to Week 240.. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Arm A: ART Alone or With Delayed ET15/94 (16%)34/94 (36.2%)83/94 (88.3%)
Arm B: ART With Immediate ET16/96 (16.7%)34/96 (35.4%)88/96 (91.7%)
Most frequent serious events
Showing 10 of 44
Most frequent serious events
EventArm A: ART Alone or With Delayed ETArm B: ART With Immediate ET
Kaposi's sarcomaNeoplasms benign, malignant and unspecified (incl cysts and polyps)9/945/96
AnaemiaBlood and lymphatic system disorders4/943/96
BacteraemiaInfections and infestations0/944/96
PneumoniaInfections and infestations2/944/96
GastroenteritisInfections and infestations3/940/96
Pleural effusionRespiratory, thoracic and mediastinal disorders0/943/96
CellulitisInfections and infestations2/942/96
Disseminated tuberculosisInfections and infestations2/940/96
Pneumonia bacterialInfections and infestations2/941/96
SepsisInfections and infestations2/942/96
Most frequent other events
Showing 10 of 52
Most frequent other events
EventArm A: ART Alone or With Delayed ETArm B: ART With Immediate ET
Blood sodium decreasedInvestigations39/9438/96
Neutrophil count decreasedInvestigations32/9436/96
Blood albumin decreasedInvestigations34/9432/96
CoughRespiratory, thoracic and mediastinal disorders20/9431/96
PyrexiaGeneral disorders25/9429/96
Haemoglobin decreasedInvestigations24/9419/96
Upper respiratory tract infectionInfections and infestations2/9418/96
Aspartate aminotransferase increasedInvestigations14/9418/96
Blood bicarbonate decreasedInvestigations15/9413/96
Pain in extremityMusculoskeletal and connective tissue disorders15/949/96

Baseline characteristics

All eligible participants who initiated study treatment.

Age, Continuous
Age, Continuous(years)Arm A: ART Alone or With Delayed ETArm B: ART With Immediate ETTotal
Median34 (28 to 41)35 (30 to 41)34 (29 to 41)
Sex: Female, Male
Sex: Female, Male(Participants)Arm A: ART Alone or With Delayed ETArm B: ART With Immediate ETTotal
Female6669135
Male282755
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)Arm A: ART Alone or With Delayed ETArm B: ART With Immediate ETTotal
Hispanic or Latino8816
Not Hispanic or Latino8386169
Unknown or Not Reported325
Region of Enrollment
Region of Enrollment(Participants)Arm A: ART Alone or With Delayed ETArm B: ART With Immediate ETTotal
Malawi303262
Brazil459
Uganda283058
Zimbabwe9716
South Africa6612
Kenya151328
Peru235
Race (NIH/OMB)
Race (NIH/OMB)(Participants)Arm A: ART Alone or With Delayed ETArm B: ART With Immediate ETTotal
Asian011
Black or African American8988177
White257
Other325
HIV-1 RNA
HIV-1 RNA(log10 copies/mL)Arm A: ART Alone or With Delayed ETArm B: ART With Immediate ETTotal
Median5.11 (4.48 to 5.62)5.10 (4.59 to 5.47)5.11 (4.53 to 5.50)
CD4 cell count, continuous
CD4 cell count, continuous(cells/mm^3)Arm A: ART Alone or With Delayed ETArm B: ART With Immediate ETTotal
Median190 (88 to 325)165 (63 to 327)184 (78 to 325)
CD4 cell count, categorized
CD4 cell count, categorized(Participants)Arm A: ART Alone or With Delayed ETArm B: ART With Immediate ETTotal
<200 cells/mm^35053103
>=200 cells/mm^3444387

3 further baseline measures are reported on the registry.

08

Study locations

8 sites
  • Instituto de Pesquisa Clinica Evandro Chagas (12101)
    Rio de Janeiro, 21045, Brazil
  • Walter Reed Project - Kenya Med. Research Institute Kericho CRS (12501)
    Kericho, 20200, Kenya
  • College of Med. JHU CRS (30301)
    Blantyre, Malawi
  • University of North Carolina Lilongwe CRS (12001)
    Lilongwe, Malawi
  • San Miguel CRS
    San Miguel, Lima, Peru
  • Wits HIV CRS
    Johannesburg, Gauteng, South Africa
  • Durban Adult HIV CRS (11201)
    Durban, 4013 SF, South Africa
  • JCRC CRS
    Kampala, Uganda
09

References and documents

Publications

  • The DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), Version 1.0, December 2004 (Clarification, August 2009).
  • Manual for Expedited Reporting of Adverse Events to DAID, Version 2.0, January 2010. http://rsc.tech-res.com/clinical-research-sites/safety-reporting/manual
  • Krown SE, Metroka C, Wernz JC. Kaposi's sarcoma in the acquired immune deficiency syndrome: a proposal for uniform evaluation, response, and staging criteria. AIDS Clinical Trials Group Oncology Committee. J Clin Oncol. 1989 Sep;7(9):1201-7. doi: 10.1200/JCO.1989.7.9.1201. PubMed 2671281 ↗
  • Cianfrocca M, Cooley TP, Lee JY, Rudek MA, Scadden DT, Ratner L, Pluda JM, Figg WD, Krown SE, Dezube BJ. Matrix metalloproteinase inhibitor COL-3 in the treatment of AIDS-related Kaposi's sarcoma: a phase I AIDS malignancy consortium study. J Clin Oncol. 2002 Jan 1;20(1):153-9. doi: 10.1200/JCO.2002.20.1.153. PubMed 11773164 ↗
  • Hosseinipour MC, Kang M, Krown SE, Bukuru A, Umbleja T, Martin JN, Orem J, Godfrey C, Hoagland B, Mwelase N, Langat D, Nyirenda M, MacRae J, Borok M, Samaneka W, Moses A, Mngqbisa R, Busakhala N, Martinez-Maza O, Ambinder R, Dittmer DP, Nokta M, Campbell TB; A5264/AMC-067 REACT-KS Team. As-Needed Vs Immediate Etoposide Chemotherapy in Combination With Antiretroviral Therapy for Mild-to-Moderate AIDS-Associated Kaposi Sarcoma in Resource-Limited Settings: A5264/AMC-067 Randomized Clinical Trial. Clin Infect Dis. 2018 Jul 2;67(2):251-260. doi: 10.1093/cid/ciy044. PubMed 29365083 ↗
  • Kang M, Grund B, Hunsberger S, Glidden D, Volberding P. Interim monitoring in a treatment strategy trial with a composite primary endpoint. Contemp Clin Trials. 2019 Nov;86:105846. doi: 10.1016/j.cct.2019.105846. Epub 2019 Sep 11. PubMed 31520741 ↗

Individual participant data

Plan to share: Undecided

10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Nov 14, 2019, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT01352117
Lead sponsor
Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections
Collaborators
National Institute of Allergy and Infectious Diseases (NIAID)
Responsible party
Sponsor
First posted
May 11, 2011
Start date
Nov 18, 2011
Primary completion
Mar 16, 2016
Completion
Nov 29, 2018
Results posted
Jul 31, 2017
Last update
Nov 14, 2019

Study contacts

Thomas B Campbell, M.D.
study chair · University of Colorado Hospital CRS
Mina C Hosseinipour, M.D.
study chair · University of North Carolina Lilongwe CRS

Oversight

Data monitoring committee
Yes
View the source record on ClinicalTrials.gov ↗

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