1

Presentation on ESPRIT & STALWART CyclingWashington ICC Group Meeting, June 2007

CCG Training SessionPrepared by: Dale C. Sattergren

ESPRIT & STALWART

2

ESPRIT StudyESPRIT stands for

Evaluation of Subcutaneous Proleukin in a Randomized International Trial

3

ESPRIT Purpose & DesignPurpose: 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.

4

Study TreatmentEligible 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.

5

IL-2 Treatment GroupIL-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.

6

Control GroupNon 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.

7

ESPRIT Re-CyclingUnfortunately, 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 IL-2 arm actually receive the treatment per protocol instructions.

8

ESPRIT Re-CyclingOtherwise, 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.

9

Christiane JonesLength and interval of cyclingHow the patient is educated and prepared for side effectsMedicines that are provided to prevent or reduce side

effects Demonstration of the subcutaneous injections and how

patients are taught to self-injectEquipment provided to patients such as needles,

thermometers, energy drinks, etc.How the nurse communicates with the patient during the

recycling processDiscussion of the typical side-effects and how they are

managedCase examples

10

IL-2 Side EffectsFlu-like symptoms, including fever and

muscle or joint painsNasal and sinus congestionNausea, vomiting and loss of appetiteDiarrheaFluid retention (swelling, edema)Dry eyes,Skin rash, itching and peelingMouth sores or dry mouthAltered sleep patterns, insomnia, anxiety, or

depressionInjection site reactions

11

Strategies for Successful Re-cycling

Make use of prophylactic medicationsRemove jewelry (due to potential for swelling)Report any recent illness of injuryDrink plenty of fluids; have food and other

essentials on-handMassage and rotate injection sites; use ice

before and after the injectionArrange for family/friends to help out if neededPlan to rest during re-cycling and to avoid heavy

activityIf there is any question or concern, contact

study personnel

12

STALWART StudyStalwart

Stands For;Study of Aldesleukin with and Without

Anti-Retroviral Therapy

13

STALWART PurposeThe 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

14

STALWART Study TreatmentEligible 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.