Safety and Efficacy of 90Y Zevalin in Nonmyeloablative Transplantation for Lymphoid Malignancies
Rituxan is an antibody made from human and mouse protein. It reacts with a certain antigen
on lymphoma cells and causes the body's immune system to destroy the lymphoma cells. 90Y
Zevalin and 111In Zevalin are murine-based antibodies combined with a radioactive agent that
can also destroy lymphoma cells. Unlike Rituxan, 90Y Zevalin cannot be traced by regular
scanning and requires indium to determine its distribution through the body.
Before treatment starts, patients will have a physical exam, including blood tests and urine
tests. Women who are able to have children must have a negative blood pregnancy test. Bone
marrow samples will be taken. For bone marrow sampling, a large needle is placed in the
hipbone after it has been numbed. The bone marrow is then withdrawn through the needle.
Patients will have a chest x-ray, computed tomography (CT) scans, an EKG, and tests of lung
Blood tests, urine tests, bone marrow sampling, and x-rays will be done as needed to track
the effects of the transplant. Patients will have transfusions of blood and platelets as
needed. Blood tests will be done daily while patients are in the hospital.
Patients in this study will receive an unlabeled antibody form of Y2B8 called rituxan by
vein followed by a dose of 111In Zevalin by vein. 111In Zevalin includes the radioactive
agent indium, which shows up when patients have x-rays or scans. The scans can show where
and how fast the drug travels in the body and how long the drug stays in the body. Doctors
need to be able to see how much of the drug goes to the tumor and how much goes to normal
organs to see if it is safe to give 90Y Zevalin on an outpatient basis. A scan will be
taken 48 to 72 hours after 111In Zevalin is given.
If the radiation in the 111In Zevalin is not a threat to normal organs and bone marrow,
patients may receive 90Y Zevalin. Seven days after the 111In Zevalin injection, patients
will receive a second dose of rituxan followed by a dose of 90Y Zevalin.
Patients will also receive fludarabine and cyclophosphamide daily for 3 days. All of the
chemotherapy drugs will be given through a catheter (plastic tube) that extends into the
large chest vein. The catheter will be left in place throughout treatment. When
chemotherapy is finished, blood stem cells from a donor will be given through the catheter.
Granulocyte colony-stimulating factor (G-CSF or GCSF), a hormone that helps the production
of blood cells, will be injected under the skin once a day until the neutrophil counts
recover in the blood. Patients will receive methotrexate for 3 days post transplant and
tacrolimus for 6 months or more to prevent graft versus host disease.
All patients will have complete checkups, including blood and urine tests 2 or 3 times
during the first 12 weeks of the study. Tumors will be measured by CT or MRI and gallium
scans. Patients will be asked to fill out a survey about quality of life issues
(maintaining normal routine, family life, social life, pain). It takes about half an hour to
fill out the survey. A bone marrow sample may be taken. A test of heart function will be
done. Checkups and tests will be done every 3 months for 1 year and then every 6 months for
4 more years.
Treatment will be given in the hospital at M. D. Anderson. Patients will need to stay in
the hospital for about 3 to 4 weeks. Patients must stay in the Houston area for about 100
days after the transplant. After that, patients will need to return to Houston from time to
time for blood tests, urine tests, and other exams.
This is an investigational study. 90Y-Zevalin is approved by the FDA for relapsed and
refractory lymphoma. Its use in this trial, however, is investigational. About 70 patients
will take part in this study. All will be enrolled at M. D. Anderson.
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Number of Participants With Graft Failure
Graft failure is defined as either lack of hematologic recovery or lack of or loss of detectable donor cells.
Issa F. Khouri, MD
M.D. Anderson Cancer Center
United States: Food and Drug Administration
|MD Anderson Cancer Center||Houston, Texas 77030-4096|