Understanding
ZIO-101
(Darinaparsin)
International Myeloma Foundation
12650 Riverside Drive, Suite 206
North Hol ywood, CA 91607 USA
Telephone:
800-452-CURE (2873)
(USA & Canada)
818-487-7455
Fax: 818-487-7454
TheIMF@myeloma.org
www.myeloma.org
6/07
Table of Contents
Introduction
5
What is Multiple Myeloma?
5
What are the Stages of
Multiple Myeloma?
6
What is Darinaparsin and
How Does it Work?
8
What are the Possible Side Effects of
Darinaparsin?
10
How is Darinaparsin Given?
11
What is the Dose and Schedule for
Darinaparsin?
11
How Can I Receive Treatment with
Darinaparsin?
11
About the IMF
12
Glossary
15
©2007, International Myeloma Foundation, North Hollywood, California
Introduction
You have been given this booklet to learn
more about a new drug cal ed Darinaparsin
(S-dimethylarsino-glutathione, ZIO-101). After
reading this booklet you should know:
n What Darinaparsin is
n How Darinaparsin works
n The possible side ef ects of Darinaparsin
n How Darinaparsin is given
This booklet is meant to provide you with
general information only. It is not meant to
replace the advice of your doctor or nurse.
Your doctor or nurse can answer questions
related to your specific treatment plan. Al
words that appear in bold type are defined
in the glossary at the end of the booklet.
What is Multiple Myeloma?
Multiple myeloma (also known as myeloma
or plasma cel neoplasm) is a malignancy of
the immunoglobulin- (antibody) producing
plasma cel s found in the bone marrow. It is
a hematologic malignancy resembling leuke-
mia. However, the malignant plasma cel s, or
myeloma cel s, rarely enter the bloodstream as
in a true leukemia. Instead, the myeloma cel s
accumulate in the bone marrow, causing:
n Disruption of normal bone marrow function,
most commonly giving rise to anemia (a low
level of red blood cel s in the bloodstream),
although reduction in white blood cel and
platelet counts can also occur
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n Damage to bone surrounding accumu-
n More than 3 areas of advanced lytic bone
lated myeloma cel s
lesions
n
n
Release of an abnormal protein, mono-
A high level of M-protein in the blood or
clonal protein (M-protein), into the blood-
urine
stream
Multiple myeloma is a serious malignancy,
n Suppression of normal immune functions,
but it is treatable. Many patients experience
observed as reduced levels of normal
a series of responses, relapses, and remis-
immunoglobulins and increased suscepti-
sions. With new treatments, the average sur-
bility to infection
vival of 5 years for patients diagnosed with
multiple myeloma may be extended.
Myeloma cel s can also grow in the form
of localized tumors or plasmacytomas.
Fol owing diagnosis, several options are
Plasmacytomas may be single or multiple
available for initial or frontline therapy. For
and either medul ary (confined within bone
patients who may be candidates for high-
marrow and bone) or extramedul ary (out-
dose therapy with transplant, various induc-
side of the bone). When there are multiple
tion regimens can be considered, including
plasmacytomas inside or outside bone, this
Thalomid® (thalidomide) with dexametha-
condition is also cal ed multiple myeloma.
sone, dexamethasone alone, or other dexa-
methasone-containing combinations. The
combination of the alkylating agent melpha-
The Stages of Multiple Myeloma
lan plus prednisone, a simple oral therapy, is
Stage I (low cell mass): Early disease.
an option for patients not considering bone
The bone structure appears normal or close
marrow (stem cel ) transplant with intravenous
to normal on x-ray images; the number of
high-dose melphalan. At the time of relapse,
red blood cel s and amount of calcium in the
blood are normal or close to normal, and the
amount of M-protein is very low.
Stage II (intermediate cell mass): An
intermediate stage between stage I and I I
Stage III (high cell mass): More
advanced disease. One or more of the
fol owing are present:
n Anemia
n A high level of calcium in the blood
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newer agents are frequently required to
n Inhibiting new blood vessel development
achieve further response. Revlimid® (lenalido-
(anti-angiogenic activity) on which myelo-
mide) is an important new agent available
ma and other cancer cel s depend for their
for use in this set ing. Velcade® (bortezomib)
survival and growth.
is also an important new agent available for
The activity of Darinaparsin against cul-
relapsed myeloma.
tured myeloma cel s and transplanted tumors
in laboratory models supports testing in
What is Darinaparsin and How
patients with multiple myeloma. Two clini-
Does it Work?
cal studies are being conducted to evalu-
ate dif erent treatment schedules in patients
Darinaparsin (S-dimethylarsino-glutathione)
with advanced/progressive myeloma who
is a novel, organic arsenic. Darinaparsin
had received at least 2 prior therapies. A
kil s human myeloma cel lines grown in
phase I/I study is investigating dosing with
the laboratory. Darinaparsin is also active
300 mg/m2 once daily for 5 consecutive
against human myelomas that have been
days every 4 weeks (treatment week 1 and
transplanted into mice. Arsenic has been
no treatment weeks 2, 3, 4). The phase I
used in its inorganic form to treat various
portion of this study is determining the pre-
diseases for over 2000 years, even though
liminary ef icacy and safety profile of this
it has been associated with undesirable
schedule.
side ef ects. As a form of organic arsenic,
The phase I study is investigating a dif erent
Darinaparsin represents a new class of smal
dosing schedule of Darinaparsin: 420 mg/
molecule cancer therapy.
m2 twice a week every 3 weeks of a 4 week
The potential anti-myeloma ef ect of Dari-
cycle (treatment weeks 1, 2, 3, and no treat-
naparsin may result from several activities:
ment week 4). The purpose of this study is to
n Disrupting the function of mitochondria,
determine preliminary ef icacy and safety.
which are smal structures within cel s that
There have been 14 patients treated at 300
provide energy, and are often referred to
mg/m2 once daily for 5 consecutive days
as the powerhouses of cel s.
every 4 weeks. In this group, 10 patients are
n Increasing the production of reactive oxy-
evaluable for response, that is, they have
gen species which can damage the DNA
received at least 2 cycles of therapy, and
and protein of myeloma cel s.
4 of them have stable disease as their best
response. Three patients have been treated
n Modifying the ability of myeloma cel s to
at 420 mg/m2 twice a week every 3 weeks
respond to factors in the bone marrow
of a 4 week cycle.
and blood that promote their growth.
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What are the Possible Side Effects
How is Darinaparsin Given?
of Darinaparsin?
Darinaparsin is given as an intravenous (I.V.)
infusion.
Common side effects associated with
Darinaparsin that have been seen in the
phase I/I and phase I trials (both dosing
What is the Dose and Schedule for
schedules) include vomiting, fatigue, and
Darinaparsin?
pain at the site of infusion in patients receiv-
ing their treatment through a peripheral line.
The most ef ective dose and schedule for
More serious side ef ects observed in a smal
treating multiple myeloma with Darinaparsin
number of patients include decreased blood
is stil being determined in clinical trials.
cel counts, confusion, and dizziness. No
clinical y important neuropathy (nerve dam-
How Can I Receive Treatment with
age), bone marrow toxicity, or cardiotoxic-
Darinaparsin?
ity (heart toxicity) has been seen during the
clinical trials so far. Your doctor or nurse can
At present, Darinaparsin is available to
provide more information in greater detail
patients with multiple myeloma and other
about these and other possible side ef ects.
types of cancer who are wil ing to partici-
pate in clinical trials. For more information
Because the safety information about
on how to enrol in a clinical trial, contact
Darinaparsin is derived from clinical trials,
the IMF.
and these clinical trials are ongoing, no
definitive conclusions about the side ef ects
IMF hotline:
can yet be made.
USA & Canada only: 800-452-CURE (2873)
Elsewhere: 818-487-7455
IMF Web site: www.myeloma.org
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About the IMF
The IMF provides programs and services to
aid in the research, diagnosis, treatment,
"One person can make a dif erence,
and management of myeloma. The IMF
Two can make a miracle."
ensures that no one must brave the myeloma
Brian D. Novis
bat le alone.
IMF Founder
We care for patients today, while working
Myeloma is a lit le-known, complex, and
toward tomorrow's cure.
often misdiagnosed bone marrow cancer that
How Can the IMF Help You?
at acks and destroys bone. Myeloma af ects
approximately 75,000 to 100,000 people
PATIENT EDUCATION
in the United States, with approximately
INFORMATION PACKAGE
20,000 new cases diagnosed each year.
Our free IMF InfoPack provides comprehensive
Although there is presently no known cure for
information about myeloma, treatment options,
myeloma, doctors have many approaches
disease management, and IMF services. It
to help myeloma patients live bet er and
includes our acclaimed Patient Handbook.
longer.
INTERNET ACCESS
The International Myeloma Foundation (IMF)
Log on to www.myeloma.org for 24-hour
was founded in 1990 by Brian and Susie
access to information about myeloma, the IMF,
education, and support programs.
Novis shortly after Brian's myeloma diagno-
sis at the age of 33. It was Brian's dream that
ONLINE MYELOMA FORUM
future patients would have easy access to
Join the IMF Internet Discussion Group at
medical information and emotional support
www.myeloma.org/listserve.html to share
throughout their bat le with myeloma. He
your thoughts and experiences.
established the IMF with the 3 goals of treat-
MYELOMA MINUTE
ment, education, and research. He sought
Subscribe to this free weekly email news-
to provide a broad spectrum of services for
let er for up-to-the-minute information about
patients, their families, friends, and health
myeloma.
care providers. Although Brian died 4 years
PATIENT & FAMILY SEMINARS
after his initial diagnosis, his dream didn't.
Meet with leading experts in myeloma treat-
Today, the IMF reaches out to an interna-
ment to learn more about recent advances in
tional membership of more than 150,000.
therapy and research.
The IMF was the first organization dedicated
MYELOMA MATRIX
solely to myeloma, and today it remains the
On our website and in print, this document is a
largest.
comprehensive guide to drugs in development
for myeloma.
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MYELOMA TODAY NEWSLETTER
Glossary
Our quarterly newslet er is available free of
charge by subscription.
Alkylating agent: A chemotherapy agent that prevents the
growth and division of new cancer cel s by inhibiting their
SUPPORT
ability to replicate DNA.
MYELOMA HOTLINE: 800-452-CURE (2873)
Anemia: A low level of red blood cel s in the blood-
Toll-free throughout the United States and
stream.
Anti-angiogenic activity:
Canada, the IMF Hotline is staf ed by trained
Ability to inhibit new blood vessel
development.
information specialists and is in frequent inter-
Antibody: A protein produced by some of the body's white
action with members of our Scientific Advisory
blood cel s that helps fight infection.
Board.
Bone marrow: A soft, spongy tissue found in most large
bones that produces red and white blood cel s and
SUPPORT GROUPS
platelets.
A worldwide network of more than 100 myelo-
Immune function: The functioning of the immune system; the
ma support groups holds regular meetings for
system of white bloodcel s and their properties that help
members of the myeloma community. The IMF
the body resist infection and some cancers.
conducts annual retreats for myeloma support
Immunoglobulin: An antibody.
group leaders.
Inorganic: Not formed by a living organism.
Intravenous (I.V.) infusion: Delivery of a drug or fluid into
RESEARCH
the body using a needle inserted into a vein.
Lysis (lytic): Dissolution or destruction of cel s.
BANK ON A CURE®
Mitochondria: Smal structures within cel s that provide
This DNA bank wil provide genetic data for
energy.
research in new drug development.
Monoclonal protein (M protein): An abnormal protein pro-
duced by myeloma cel s that accumulates in and damages
THE INTERNATIONAL STAGING SYSTEM (ISS)
bone and bone marrow. A high level of M protein indi-
This updated staging system for myeloma wil
cates that myeloma cel s are present in large numbers.
enhance physicians' ability to select the most
Multiple myeloma: A cancer arising from the plasma cel s
appropriate treatment for each patient.
in the bone marrow. The plasma cel s in patients with
multiple myeloma form abnormal antibodies, possibly
RESEARCH GRANTS
damaging the bone, bone marrow, and other organs.
Leading the world in col aborative research
Neoplasm: Cancer.
and achieving extraordinary results, the IMF
Organic: Formed by a living organism, i.e., an animal
Grant Program supports both junior and senior
or plant.
researchers working on a broad spectrum of
Plasma cell: A type of white blood cel that produces
projects. The IMF has at racted many young
antibodies.
investigators into the field of myeloma who
Plasmacytoma: A tumor made up of cancerous plasma
cel s.
remain in the field and actively pursue a cure
Side effect: An ef ect caused by treatment with a drug. The
for the disease.
term usual y refers to an unwanted ef ect, but some side
ef ects may be beneficial.
White blood cell: A cel made by the bone marrow that
helps fight infection and/or disease.
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