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
2
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.
3
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.
4
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.
5
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.
6
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.
7
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.
8
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
9
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
10
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
11
STALWART Study
 Stalwart
 Stands For;
 Study of Aldesleukin with and Without
 Anti-Retroviral Therapy
12
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
13
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.
14