Y Zevalin, BEAM and Rituximab In Autologous Stem Cell Transplantation (ASCT) For Lymphoma
18 Years
65 Years
Both
Lymphoma
Trial Information
Y Zevalin, BEAM and Rituximab In Autologous Stem Cell Transplantation (ASCT) For Lymphoma
BEAM chemotherapy is the standard treatment for lymphoma. BEAM is a combination of
chemotherapy drugs (carmustine, cytarabine, etoposide, and melphalan). Rituximab is an
antibody made from human and mouse proteins. It reacts with a certain molecule on the
surface of lymphoma cells and helps the body's immune system destroy the lymphoma cells. 90Y
Zevalin is also an antibody made from mouse proteins. However, it has a particle of
radiation attached to it. 90Y Zevalin works by attaching to lymphoma cells, and the
radiation particle destroys the lymphoma cell.
For this study, you will receive rituximab by vein followed by a dose of 111In Zevalin by
vein (over 15 minutes). 111In Zevalin is different from the study drug (90Y Zevalin).
111In Zevalin has a different type of radioactive particle attached to it. This particle
does not kill lymphoma cells, but it can be "seen" inside the body using a special camera
(like an x-ray). 111In Zevalin is being used to predict how fast the study drug will travel
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 determine if it is
safe to give 90Y Zevalin on an outpatient basis. A scan will be done as soon as 111In
Zevalin is given and about 2-24 hours later. Scans will also be done 2-3 days later. If
the radiation in the 111In Zevalin is not a threat to normal organs and bone marrow, you may
receive 90Y Zevalin. Seven (7) days after the 111In Zevalin injection, you will receive a
second dose of rituximab followed by a dose of 90Y Zevalin by vein (over 15 minutes).
Seven (7) days after the 90Y Zevalin injection, you will receive the BEAM combination of
chemotherapy. You will receive carmustine (over 2 hours) on Day 1 of chemotherapy. You
will receive cytarabine (over 2 hours) followed by etoposide (over 4 hours) twice a day on
Days 2 through 5. On Day 6, you will receive melphalan (over 20 minutes). A catheter
(small flexible tube) will be placed in a large vein in your chest so that the chemotherapy
drugs can be given to you more easily. This is called a central venous catheter. All of
the chemotherapy drugs will be given through the central venous catheter.
One day after finishing the chemotherapy, the stem cells that were collected earlier will be
given back to you by vein over about 30 minutes. Starting on the same day, you will receive
treatments with G-CSF by injection under the skin once a day. Treatment with G-CSF will
continue until your blood counts reach a certain level.
You will receive rituximab by vein (over 6 to 8 hours) on the day after the transplant and
again 1-week later.
Blood tests (about 1-2 tablespoons), urine tests, bone marrow collections, and x-rays will
be done as needed to track the effects of the transplant. You will have transfusions of
blood and platelets as needed. Blood tests (about 1 tablespoon) will be done once a day
while you are in the hospital.
Blood tests (about 1-2 tablespoons), urine tests, bone marrow collections, x-rays, CT scans,
and PET scans will be done every 3 months for 1 year and then every 6 months for 5 years to
check on the status of the disease.
You will be asked to give some extra blood samples (around 1 tablespoon each) at study entry
and upon return visits to M. D. Anderson. These samples will be used to test for certain
molecules in the blood (HAMA and soluble CD20) and to check on the level of rituximab in the
blood.
Treatment will be given in the hospital at M. D. Anderson. You will need to stay in the
hospital for about 3 to 4 weeks. You should stay in the Houston area for about 2 to 4 weeks
after the transplant. After that, you will need to return to Houston from time to time for
blood tests, urine tests, and other exams.
This is an investigational study. 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. All other drugs used in this study are FDA approved and are
commercially available. Up to 60 participants will take part in this study. All will be
enrolled at M. D. Anderson.
Inclusion Criteria:
1. Relapsed CD20-positive B-cell non-Hodgkin's lymphoma (NHL) (demonstrated in lymph
nodes or bone marrow), chemosensitive (at least Partial Remission [PR]).
2. No anti-cancer therapy started within three weeks, prior to study initiation, and
fully recovered from all toxicities associated with prior surgery, radiation
treatments, chemotherapy, or immunotherapy. No prior Rituximab within three weeks of
starting therapy.
3. No prior radioimmunoconjugate therapy.
4. If patients had prior radiation, this should have not involved more than 25% of the
bone marrow.
5. An IRB-approved signed informed consent.
6. Age: 18 to 65 years of age.
7. Acceptable hematologic status within two weeks prior to patient registration,
including: Absolute neutrophil count ([segmented neutrophils + bands] * total white
blood count [WBC]) > 1,500/mm3. Platelet counts > 100,000/mm3.
8. Patients determined to have <10% bone marrow involvement with lymphoma within four
weeks before stem cell collection as defined by bilateral aspirates and biopsies.
9. Prestudy performance status of 0, 1, or 2 according to the World Health Organization
(WHO).
10. Female patients included must not be pregnant or lactating.
11. Men and women or reproductive potential who are following acceptable birth control
methods (as determined by the treating physician, however abstinence is not an
acceptable method).
12. Patients who have previously been treated on Phase II drugs can be included if no
long-term toxicity is expected, and the patient has been off the drug for four or
more weeks with no significant post treatment toxicities observed
13. Patients should have at least 4 * 106 CD34+/kg peripheral stem cells collected.
Whenever possible, 1 to 2 * 106 CD34+/kg, for the first 10 patients and held for 1
year in case of graft failure. If graft failure does not occur in the first 10
patients, backup cells will not be required for subsequent patients.
Exclusion Criteria:
1. Patients with impaired bone marrow reserve, as indicated by one or more of the
following: Prior myeloablative therapies with autologous bone marrow transplantation
(ABMT) or peripheral blood stem cell (PBSC) rescue Platelet count < 100,000 cells/mm3
Hypocellular bone marrow Marked reduction in bone marrow precursors of one or more
cell lines (granulocytic, megakaryocytic, erythroid) History of failed stem cell
collection of > 4*106 CD34+/kg
2. Prior radioimmunotherapy.
3. Presence of central nervous system (CNS) lymphoma.
4. Patients with chronic lymphocytic lymphoma.
5. Patients with human immunodeficiency virus (HIV) or acquired immune deficiency
syndrome (AIDS)-related lymphoma.
6. Patients with abnormal liver function: total bilirubin > 1.5 mg/dl
7. Patients with abnormal renal function: serum creatinine > 1.6 mg/dl
8. Patients who have received prior external beam radiation therapy to >25% of active
bone marrow (involved field or regional).
9. Serious nonmalignant disease or infection which, in the opinion of the investigator
and/or the sponsor, would compromise other protocol objectives.
10. Corrected carbon monoxide diffusion in the lung (DLCO) <50% and forced expiratory
volume in 1 second (FEV1) or forced vital capacity (FVC) < 50% predicted.
11. Cardiac ejection fraction (EF) < 50% by 2-D Echogram.
12. Pleural effusions.
13. Prior radiation to lungs.
14. Abnormal cytogenetics, filter in situ hybridization (FISH) (-5, -7, 11q23)
Type of Study:
Interventional
Study Design:
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Median Overall Survival
Outcome Description:
Number of participants alive following treatment at 5 years then annual follow up till disease progression. Evaulations done every 3 months for 1 year and then every 6 months for 5 years to check on the status of the disease, with long-term follow up as needed.
Outcome Time Frame:
8 years (study duration)
Safety Issue:
No
Principal Investigator
Issa F. Khouri, MD,BS
Investigator Role:
Principal Investigator
Investigator Affiliation:
UT MD Anderson Cancer Center
Authority:
United States: Food and Drug Administration
Study ID:
ID03-0123
NCT ID:
NCT01538472
Start Date:
September 2003
Completion Date:
November 2011
Related Keywords:
- Lymphoma
- Lymphoma
- Relapse B-cell CD20+ non-Hodgkin's lymphoma
- High-dose BEAM chemotherapy
- Y Zevalin
- In Zevalin
- Rituxan
- Rituximab
- BCNU
- Carmustine
- BiCNU
- VP-16
- Ara-C
- Cytarabine
- Cytosar
- DepoCyt
- Cytosine Arabinosine Hydrochloride
- Melphalan
- Alkeran
- G-CSF
- Filgrastim
- Neupogen
- Stem cell infusion
- Autologous stem cell transplantation
- Lymphoma
Name | Location |
|---|---|
| UT MD Anderson Cancer Center | Houston, Texas 77030 |
