Transcript ppt - CPCRA
ESPRIT & STALWART
Presentation on ESPRIT & STALWART Cycling
Washington ICC Group Meeting, June 2007
CCG Training Session
Prepared by: Dale C. Sattergren
ESPRIT Study
ESPRIT stands for
Evaluation of Subcutaneous Proleukin in a
Randomized International Trial
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ESPRIT Purpose & Design
Purpose: To compare the effects of subcutaneous
recombinant Interelukin-2 and no SC rIL-2 on disease
progression and death over a 5 year period in patients with
HIV infection and CD4 cell count of > 300 who are taking
combination antiretroviral therapy.
ESPRIT was designed to investigate the strategy of using
intermittent cycles of subcutaneous IL-2 to increase CD4
cells.
The aim was to maintain participants’ CD4 cell counts at
twice their baseline level or greater than 1000 cells/mm if
participants entered the trial with more than 500/mm cells.
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Study Treatment
Eligible patients were randomized to receive SC rIL-2 therapy or
no SC rIL-2. Recombinant IL-2 at a dose of 7.5 MIU daily is given
for 5 consecutive days every 8 weeks for at least 3 cycles. Thus,
during the first 6 months of follow-up, all patients randomized
to SC rIL-2 will receive 3 cycles unless toxicities or other
contraindications develop
After the first 3 cycles, additional cycles will be given at the
discretion of each patient in consultation with their physician
As a guide, patients who enter with a CD4 cell count< 500 will be
encouraged to receive additional cycles of therapy to maintain
their CD4 level > twice baseline.
Those entering with CD4 > 500 cells will be encourage to receive
additional cycles of therapy to maintain their CD4 > 1000 cells.
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IL-2 Treatment Group
IL-2 Group: This group will receive IL-2. IL-2 will be given at a
dose of 7.5 million international units (MIU) by injection below
the skin, twice a day for 5 days in a row. This will be followed by
7 weeks when you do not get IL-2. Another 5 day period of
getting IL-2 by injection will follow after the 7 weeks of not
getting IL-2. This routine will be repeated a third time. Then
you may continue to get IL-2 by injection for 5 days in a row,
starting no closer than 6 weeks apart, if your health care provider
determines that IL-2 is helping you. If you were assigned to the
arm that receive IL-2, your health care provider or study nurse
would discuss with you, how you would receive your IL-2
injections.
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Control Group
Non IL-2 Group: This group would not
receive IL-2 during the study. This group is
very important to determine whether or not
IL-2 makes a difference in slowing the
progression of HIV disease.
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ESPRIT Re-Cycling
Unfortunately, not many IL-2 participants continue to
use IL-2 to maintain these target CD4 cell goals,
although over half did reach their goal at some point in
the trial.
The DSMB stressed (very strongly) that we need to do
more to make sure that participants assigned to the IL2 arm actually receive the treatment per protocol
instructions.
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ESPRIT Re-Cycling
Otherwise, we may end up having spent many years of
time and effort only to fail to answer the study
question, as we will not be truly comparing individuals
taking IL-2 treatment to those taking no IL-2
treatment.
This brings us to the topic of the Re-cycling.
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Christiane Jones
Length and interval of cycling
How the patient is educated and prepared for side effects
Medicines that are provided to prevent or reduce side
effects
Demonstration of the subcutaneous injections and how
patients are taught to self-inject
Equipment provided to patients such as needles,
thermometers, energy drinks, etc.
How the nurse communicates with the patient during the
recycling process
Discussion of the typical side-effects and how they are
managed
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IL-2 Side Effects
Flu-like symptoms, including fever and muscle or joint
pains
Nasal and sinus congestion
Nausea, vomiting and loss of appetite
Diarrhea
Fluid retention (swelling, edema)
Dry eyes,
Skin rash, itching and peeling
Mouth sores or dry mouth
Altered sleep patterns, insomnia, anxiety, or
depression
Injection site reactions
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Strategies for Successful Re-cycling
Make use of prophylactic medications
Remove jewelry (due to potential for swelling)
Report any recent illness of injury
Drink plenty of fluids; have food and other essentials
on-hand
Massage and rotate injection sites; use ice before and
after the injection
Arrange for family/friends to help out if needed
Plan to rest during re-cycling and to avoid heavy
activity
If there is any question or concern, contact study
personnel
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STALWART Study
Stalwart
Stands For;
Study of Aldesleukin with and Without
Anti-Retroviral Therapy
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STALWART Purpose
The purpose of this study is to compare the effects of
subcutaneous (SC) recombinant interleukin 2 (rIL-2)
administered with and without concomitant pericycle
highly active antiretroviral therapy (HAART) to no
therapy on CD4 count in patients with HIV-1 infection
and CD4 count >300 cells/mm3.
DESIGN: International, phase II, multi-site, open
label, randomized, controlled trial
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STALWART Study Treatment
Eligible participants will be randomized in a 1:1:1 fashion to one of
three groups.
GROUP A: No therapy
GROUP B: rIL-2 7.5 million international units (MIU)
subcutaneous (SC) twice a day (BID) for 5 consecutive days every 8
weeks for 3 cycles then as needed to maintain CD4 cell counts at or
above goal.
GROUP C: rIL-2 7.5 MIU SC twice a day, for 5 consecutive days
every 8 weeks with HAART beginning 3 days prior to each cycle,
continuing through the cycle, and stopping 2 days after the last day
of rIL-2 administration (For maximum of 10 days of HAART with
each cycle) for 3 cycles then as needed to maintain CD4 cell counts
at or above goal.
Participants randomized to Groups B and C will receive cycles of
rIL-2 unless toxicities or other contraindications develop.
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