Current Clinical Trials, Studies & Grants According to Dr. Kevin Hahn, Medical Oncologist,
Gulf Coast Veterinary Oncologists, "the treatment of cancer in animals
utilizes many of the same methods available in human medicine. Chemotherapy,
radiation therapy, hypothermia, immunotherapy and photodynamic therapy are
all part of the arsenal assembled to fight cancer in the pet animal. Most
clinical research trials investigating new methods of cancer diagnosis or
treatment are conducted at colleges of veterinary medicine.
Although
considered "experimental", effectiveness of the treatment has been proven in
laboratory animals, safety has been demonstrated in normal dogs or cats, and
the therapy is considered to be of potential benefit to the patient.
Patients entering a clinical trial must be carefully monitored. Adherence to
the treatment protocol is of vital importance to the veterinarian, the pet
owner, and to future pets with cancer to ensure that the best in therapy and
patient care is available.
When a patient treated in a clinical trial dies,
a necropsy (autopsy) must be conducted to know the entire effect of the
treatment; positive and negative. Many naturally occurring cancers in pet
animals closely resemble human cancer and provide meaningful systems for
cancer research to benefit both man and animals. The veterinary facility
providing the clinical trial, with owner's permission, may provide specimens
obtained from the patient (blood, urine, and/or tumor samples) to basic
researchers to gain additional information that may benefit present and
future cancer patients.
It is important to remember, research is not
conducted on the pet itself. If you believe your pet with cancer might
benefit from participating in a clinical trial or you would like additional
information regarding a specific clinical trial, please check out the
following Clinical Trial links.
Bone Marrow
Transplants
Dr. Sullivan at the Bellingham Veterinary & Critical Care Centre Dr. Ed Sullivan, a veterinarian at the Bellingham Veterinary Critical Care Centre,
located in Bellingham, Washington, has been extraordinary at "pushing the
envelope", trying to get treatment for desperately sick animals. He has been working
with the researchers at the Fred Hutchinson Cancer Research Centre, located in Seattle,
Washington, a world renowned facility for cancer treatment.
JAN 7, 2012 UPDATE from
Dr. Sullivan: I wanted to give you a brief update on our progress with the
bone marrow transplant cases over the last few years. Collectively
we are approaching 100 cases. The majority have been completed at
NCSU, with additional cases here, LA, and San Diego. After a few
years of testing different doses of consolidation chemotherapy,
various mobilization strategies, and an escalating TBI dosage, we
have settled on a protocol that is acceptably tolerated. We also
have good PCR markers for both B and most T cell lymphomas (the PCR
is run by Dr. Steele) for identification of molecular remission,
hematopoietic harvest quality, and monitoring post BMT. We have also
set up a DLA matching lab at FHCRC on a pay-for-service basis, and
they have been able to rapidly identify related donor-recipient
pairs for allogeneic transplants. About 35% of the autologous
patients are long term survivors (over 2 years); and with a small
number of allogeneic patients there has been 65% long term survival.
These numbers are close to what is expected with humans. I suspect
the autologous results will be somewhat better since many of the
most recent cases are the ones that had the optimal dosing.
We have been able to bring the price down to a reasonable
level--currently 12-15K depending upon the size of the dog and
facility doing the transplant. A large portion of this cost is the
neupogen ( 2500) and the TBI (3000). If we could come up with a
cheaper source of neupogen, or better yet, a source of canine
recombinant GCSF, that would be great. I keep working on this.
In addition, there is a new apheresis platform, the Optia from
Caridian BCT, that is replacing the COBE Spectra. We have one of
these units, and it is faster and much simpler to use.
I continue to believe there will be improvements in the protocol,
better conditioning regimens (we use cytoxan now), cytogenetics for
clonal identification, haploidentical protocols, reduced intensity
protocols, and a DLA matching system that can identify unrelated DLA
identical donors. I also believe there are many other hematopoietic
malignancies that will be treatable with both autologous and
allogenic BMT procedures--including the histiocytic diseases. In
humans, mixed donor/recipient chimerism is sufficient to control
hemophagocytic histiocytosis (not sure why this is the case), so a
reduced intensity allogeneic bmt is sufficient to get disease
control. It would be interesting to see if this is the case for dogs
as well.
A little farther out there is the possibility of allogeneic BMT in
conjunction with a whole cell tumor vaccine as a treatment for solid
tumors. We did this with one dog with fibrosarcoma, and when the dog
died a few years later he was free of fibrosarcoma.
NOV 25, 2007 UPDATE from
Dr. Sullivan: Bone marrow transplantation using hematopoietic stem cells (stem
cells that can differentiate into all blood cell lines) has long
been used in human medicine to treat many otherwise fatal
malignancies and other bone marrow disorders. Much of the
pioneering research that made transplantation possible was completed
with dogs over 30 years ago, and although the techniques were well
described, they were not developed for use in dogs as patients due
to the costs and complexities of the procedures. Recent
scientific discoveries involving the identification of donor
recipient pairs, as well as the availability of
sophisticated veterinary supportive care, coupled with the desire of
pet owners to seek treatments for traditionally incurable
conditions, has created an environment in which bone marrow
transplantation (hematopoietic stem cell transplants--HSCT) for dogs
with naturally occurring diseases is feasible.
Our work over the last four years has focused on
the practical application of HSCT for dogs with lymphoma, leukemia,
multiple myeloma, malignant histiocytosis, and other bone marrow
diseases. There are two main types of transplants, one using the
patient's own stem cells to reconstitute the bone marrow after
chemotherapy and total body irradiation--an autologous transplant.
The second type--an allogeneic transplant--uses stem cells from a
donor that has matching major histocompatibility complex
antigens--in dogs known as dog leukocyte antigens, or DLA--to
reconstitute the bone marrow. Both types of transplants have the
potential to achieve a cure, however, they also have pros and cons
that can make one option more desirable over the other. In most
situations, it is best to plan for both procedures, then chose one
when it is determined whether or not a donor can be found.
Some procedures are completed in preparation of
both types of transplants. These include complete staging of the
disease (with lymphoma the subtype, B or T cell) as well as the
degree of organ involvement. It is also important that a tumor
sample sent to us before chemotherapy has started so we can identify
the tumor clone, using flow cytometry and gene rearrangements. This
information will be used to confirm remission prior to the
transplant as well as for monitoring for relapse of disease after
the transplant. Additionally, a large tumor sample (5gm or more)
can be used produce an anti-tumor vaccine (either whole cell or
anti-idiotype for B Cell lymphoma) that can be used after the
transplant to increase an anti tumor immune response. Some of these
tumor cells will also be set up in cell culture as well as
cryopreserved for future use in generating additional vaccine.
After initial staging and submission of tumor
samples to the lab, chemotherapy can be started. Any standard
induction protocol can be used, and after 8 weeks of therapy, we
take blood and lymph node samples to confirm remission. During this
time an effort to find any donors is made--it is important to do
this quickly, as it can take a long time to find the potential
donors and speak with them about participating in a transplant.
If a suitable donor is identified, then an
allogeneic transplant is scheduled three weeks after the last dose
of chemotherapy. If no donor is found, then an autologous
transplant is scheduled.
To date, we have completed three allogeneic
transplants and three autologous transplants. Two of the allogeneic
patients are long term disease free survivors (one is 4 years since
the original diagnosis and the second is just over 2 years since the
original diagnosis). A third allogeneic patient relapsed and died
with disease progression after 20 months. One of the autologous
transplant patients died with disease progression shortly after the
transplant--she was on the third relapse at the time, and we were
only hoping to rescue her until a donor could be found. A second
autologous dog had relapse of disease 13 months after the initial
diagnosis, however, he went back into remission with chemotherapy
and is currently in remission with stable disease. The third
autologous patient has just recently been completed--so far it is
going well, but it is too soon to know the outcome.
In the future, it may be possible to complete allogeneic transplants
in combination with a tumor vaccine to treat other types of cancer.
In this scenario, an allogeneic transplant is done followed by
vaccination of the donor with a killed, whole cell tumor vaccine.
Once the donor exhibits an immune response to the vaccine,
lymphocytes are collected from the donor and given to the recipient
(the recipient already is engrafted with hematopoietic stem cells
from the donor). These stimulated lymphocytes potentially will
mobilize the new immune system in the recipient to recognize the
original tumor as abnormal and eliminate it. This scenario is
currently being tested in our facility.
If you have a dog with lymphoma, or know of one, they may be eligible for this treatment.
This is a fantastic breakthrough. Dr. Sullivan is also trying to set up funding so that
those in need of financial assistance, can afford treatment. You or your veterinarian can
call the Bellingham Veterinary and Critical Care Centre, at 360-734-0720. They are located
at 720 Virginia Street, Bellingham, WA USA, 98225.
Since 2008, NC State has been providing bone marrow transplants.
Canine bone marrow transplants at NC State University's College of
Veterinary Medicine are providing a rich source of new oncology research
knowledge.
Canine lymphoma is one of the most common
types of cancer in dogs. While the survival rate with current treatments is
extremely low (about 0 to 2 percent) the cure rate for dogs that have
received a bone marrow transplant is at least 30 percent.
The relatively new procedure involves the use of leukaphoresis machines that
are designed to harvest healthy stem cells from the peripheral blood. The
machines are used in conjunction with drug therapy to harvest stem cells
that have left the patient's bone marrow and entered the bloodstream. The
harvested cancer-free cells are then reintroduced into the patient after
total body radiation is used to kill residual cancer cells left in the body.
This treatment is called peripheral blood stem cell transplantation.
The harvesting procedure itself takes six hours and the patient remains in
the hospital for two weeks following the procedure. The bone marrow
transplant process is completely painless for dogs, although the dogs do
experience some GI distress, manifested mainly as diarrhea, from the total
body radiation.
This facility is located at 4700 Hillsborough
Street, Raleigh, NC 27606 and can be reached at (919) 513-6500.
Dog Disease Research at the Broad Institute
Now that The Broad Institute has the dog genome sequence, they are putting it to
use. The goal is to understand – and ultimately treat – the genetic causes of
disease in dogs as well as their human companions. This important research
cannot proceed without the dog community's participation. The Broad Institute
needs DNA samples from purebred dogs suffering from the diseases they are
studying (described below), as well as from older, healthy dogs from the breeds
they are studying. Sending DNA
samples Information for
veterinarians More information on the
Institute's research Printable
brochure (PDF)
Cancers: Cancer affects 30-50% of all
dogs. A higher incidence in certain breeds suggests that genetic risk factors
exist and can be identified. Many dog cancers are clinically similar to human
cancers, including several that they are working on.
Osteosarcoma (Bone cancer): Osteosarcoma is the most
common bone tumor of dog. This cancer develops in the bone, usually the
limbs, and as the tumor grows it becomes progressively more painful for the
dog and can result in lameness. Often these tumors metastasize to the lungs.
Giant breeds are at the greatest risk for developing osteosarcomas. Breeds
needed for study: Rottweilers, Greyhounds, Mastiffs, Leonbergers, Golden
Retrievers, Irish Wolfhounds, Great Pyrenees, Great Danes, Borzoi and
Scottish Deerhounds
Hemangiosarcoma: Hemangiosarcomas are rapidly growing
and highly invasive, blood-fed tumors. Blood vessels grow from the tumor and
often cause death through excessive blood loss due to rupturing of the
tumor. Breeds needed for study: Golden Retrievers, Labrador Retrievers,
Chinese Shar-Peis, Boxers, Pugs, and Rhodesian Ridgebacks
Mast Cell Tumors (MCT): MCTs are cancerous
proliferations of mast cells. Although they can and will spread throughout
the body, the danger from MCTs comes from the secondary damage caused by the
release of chemicals the tumors produce. These chemicals can cause systemic
problems that include gastric ulcers, internal bleeding, and a range of
allergic manifestations. Breeds needed for study: Golden Retrievers,
Labrador Retrievers, German Shepherds, Pugs, Shar-Peis and Boxers
Lymphoma: A cancer of the lymphocytes that can occur
in the lymph nodes, spleen, liver, and other organs. Characteristics are
high white blood cell count, swollen lymph glands, lethargy, and loss of
appetite. It is a treatable cancer, but if left untreated, it will
eventually lead to death. A number of B- and T-cell subtypes exist. Breeds
needed for study: Golden Retrievers, Cocker Spaniels, Rottweilers and Boxers
Mammary tumors: Tumors of the mammary gland are the
most common tumors found in unspayed female dogs. Several subtypes exist but
may segregate in the same families. Breeds needed for study: English
Springer Spaniels, Boxers and Cocker Spaniels
Melanoma (skin cancer): Melanoma is a cancer of
melanocytes (the pigment-producing cells of the skin). Irregular cells
develop when the melanocytes erratically multiply and invade surrounding
tissue. Malignant melanomas can spread from the original tumor and travel
through the blood to other vessels and organs. Breeds needed for study:
Scottish Terriers, Cocker Spaniels, Labrador Retrievers, Rottweilers, and
other breeds.