Safety and Efficacy of 90Y Zevalin in Nonmyeloablative Transplantation for Lymphoid Malignancies
Study Details
Study Description
Brief Summary
The goal of this clinical research study is to see if low intensity chemotherapy given together with the new drug 90Y Zevalin, followed by a transplant of blood or marrow stem cells from a donor can increase the length of remission in patients with leukemia and lymphoma. The safety of this treatment will also be studied.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1/Phase 2 |
Detailed Description
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 The bone marrow is then withdrawn through the needle.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 function.
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: 90Y Zevalin in ASCT Allogeneic Stem Cell (AST) Transplantation with 90Y Zevalin/Cyclophosphamide/Fludarabine as a preparative regimen. |
Drug: Zevalin Radioimmunotherapy
Escalating single dose of 90Y Zevalin 0.2-0.3-0.4 mCi/kg
Other Names:
Drug: Rituximab
250 mg/m^2 on day 1 and day 8
Other Names:
Drug: Fludarabine
30 mg/m^2/day for 3 days
Other Names:
Drug: Cyclophosphamide
750 mg/m^2/day for 3 days, given on the same days as fludarabine, at 4-hour intervals
Other Names:
Procedure: Allogeneic Stem Cell Transplantation
Allogeneic stem cell transplantation 2 days after chemotherapy
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Number of Participants With Graft Failure [100 days]
Graft failure is defined as either lack of hematologic recovery or lack of or loss of detectable donor cells.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Patients in relapse or considered at high risk for relapse or refractory CD-20-positive B-cell NHL or CLL. Patients considered for high risk of relapse are patients who do not achieve complete response (CR) with frontline chemotherapy, CLL is Richter's and CLL with high risk chromosomal abnormalities.
-
Measurable disease.
-
Age 18-70 years, expected survival >/= 3 months, performance status 0 to 2.
-
Availability of a matched related donor.
-
</+ 50% bone marrow involvement.
-
CLL with </+ 10,000 circulating lymphocytes.
-
Availability of a matched related or unrelated donor.
Exclusion Criteria:
-
Prior myeloablative therapies or radioimmunotherapy.
-
Prior external beam radiation therapy to >25% of active bone marrow.
-
Prior therapy with 90Y Zevalin or Campath.
-
CNS lymphoma, HIV, HTLV-1 positivity, some creatinine >1.6 mg/dl or serum bilirubin
1.5 mg/dl.
-
Pregnancy or lactation.
-
Symptomatic pulmonary or cardiac disease.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | MD Anderson Cancer Center | Houston | Texas | United States | 77030 |
Sponsors and Collaborators
- M.D. Anderson Cancer Center
- Biogen
Investigators
- Principal Investigator: Issa F. Khouri, MD, M.D. Anderson Cancer Center
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.- ID01-233
Study Results
Participant Flow
| Recruitment Details | Recruitment Period: October 30, 2002 to September 21, 2010. All participants were recruited at The University of Texas (UT) MD Anderson Cancer Center. |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | 90Y Zevalin in ASCT |
|---|---|
| Arm/Group Description | Allogeneic Stem Cell (AST) Transplantation with 90Y Zevalin/Cyclophosphamide/Fludarabine as a preparative regimen. Rituximab : 250 mg/m^2 on day 1 and day 8 Allogeneic Stem Cell Transplantation : Allogeneic stem cell transplantation 2 days after chemotherapy Cyclophosphamide : 750 mg/m^2/day x 3, given on the same days as fludarabine, at 4-hour intervals Zevalin Radioimmunotherapy : Escalating single dose of 90Y Zevalin 0.2-0.3-0.4 mCi/kg Fludarabine : 30 mg/m^2/day x 3 |
| Period Title: Overall Study | |
| STARTED | 70 |
| COMPLETED | 70 |
| NOT COMPLETED | 0 |
Baseline Characteristics
| Arm/Group Title | 90Y Zevalin in ASCT |
|---|---|
| Arm/Group Description | Allogeneic Stem Cell (AST) Transplantation with 90Y Zevalin/Cyclophosphamide/Fludarabine as a preparative regimen. Rituximab : 250 mg/m^2 on day 1 and day 8 Allogeneic Stem Cell Transplantation : Allogeneic stem cell transplantation 2 days after chemotherapy Cyclophosphamide : 750 mg/m^2/day x 3, given on the same days as fludarabine, at 4-hour intervals Zevalin Radioimmunotherapy : Escalating single dose of 90Y Zevalin 0.2-0.3-0.4 mCi/kg Fludarabine : 30 mg/m^2/day x 3 |
| Overall Participants | 70 |
| Age (Count of Participants) | |
| <=18 years |
0
0%
|
| Between 18 and 65 years |
61
87.1%
|
| >=65 years |
9
12.9%
|
| Sex: Female, Male (Count of Participants) | |
| Female |
23
32.9%
|
| Male |
47
67.1%
|
| Region of Enrollment (participants) [Number] | |
| United States |
70
100%
|
Outcome Measures
| Title | Number of Participants With Graft Failure |
|---|---|
| Description | Graft failure is defined as either lack of hematologic recovery or lack of or loss of detectable donor cells. |
| Time Frame | 100 days |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | 90Y Zevalin in ASCT |
|---|---|
| Arm/Group Description | Allogeneic Stem Cell (AST) Transplantation with 90Y Zevalin/Cyclophosphamide/Fludarabine as a preparative regimen. Rituximab: 250 mg/m^2 on day 1 and day 8 Allogeneic Stem Cell Transplantation : Allogeneic stem cell transplantation 2 days after chemotherapy Cyclophosphamide : 750 mg/m^2/day x 3, given on the same days as fludarabine, at 4-hour intervals Zevalin Radioimmunotherapy : Escalating single dose of 90Y Zevalin 0.2-0.3-0.4 mCi/kg Fludarabine : 30 mg/m^2/day x 3 |
| Measure Participants | 70 |
| Number [participants] |
1
1.4%
|
Adverse Events
| Time Frame | 9 Years and 1 Month | |
|---|---|---|
| Adverse Event Reporting Description | ||
| Arm/Group Title | 90Y Zevalin in ASCT | |
| Arm/Group Description | Allogeneic Stem Cell (AST) Transplantation with 90Y Zevalin/Cyclophosphamide/Fludarabine as a preparative regimen. Rituximab : 250 mg/m^2 on day 1 and day 8 Allogeneic Stem Cell Transplantation : Allogeneic stem cell transplantation 2 days after chemotherapy Cyclophosphamide : 750 mg/m^2/day x 3, given on the same days as fludarabine, at 4-hour intervals Zevalin Radioimmunotherapy : Escalating single dose of 90Y Zevalin 0.2-0.3-0.4 mCi/kg Fludarabine : 30 mg/m^2/day x 3 | |
All Cause Mortality |
||
| 90Y Zevalin in ASCT | ||
| Affected / at Risk (%) | # Events | |
| Total | / (NaN) | |
Serious Adverse Events |
||
| 90Y Zevalin in ASCT | ||
| Affected / at Risk (%) | # Events | |
| Total | 7/70 (10%) | |
| Blood and lymphatic system disorders | ||
| Neutropenia | 1/70 (1.4%) | 1 |
| Cardiac disorders | ||
| Thrombosis | 1/70 (1.4%) | 1 |
| Gastrointestinal disorders | ||
| C-Diff Colitis | 1/70 (1.4%) | 1 |
| Death due to G.I. GVHD | 1/70 (1.4%) | 1 |
| Death Due to Chronic Liver/G.I GVHD | 1/70 (1.4%) | 1 |
| General disorders | ||
| Right Inguinal hernia | 1/70 (1.4%) | 1 |
| Infections and infestations | ||
| Sepsis | 1/70 (1.4%) | 1 |
| Viral Hepatitis B reactivation | 1/70 (1.4%) | 1 |
| Renal and urinary disorders | ||
| Acute renal failure | 1/70 (1.4%) | 1 |
| Respiratory, thoracic and mediastinal disorders | ||
| Pneumonia | 2/70 (2.9%) | 2 |
| Prolonged Hospitalization, Generalized Weakness/Pneumonia | 1/70 (1.4%) | 1 |
| Skin and subcutaneous tissue disorders | ||
| secondary malignancy- Melanoma | 1/70 (1.4%) | 1 |
| Secondary Malignancy-Early Nodular Basal Cell Carcinoma | 1/70 (1.4%) | 1 |
Other (Not Including Serious) Adverse Events |
||
| 90Y Zevalin in ASCT | ||
| Affected / at Risk (%) | # Events | |
| Total | 70/70 (100%) | |
| Blood and lymphatic system disorders | ||
| Neutropenia | 1/70 (1.4%) | 1 |
| Cardiac disorders | ||
| Hypertension | 10/70 (14.3%) | 10 |
| Edema | 5/70 (7.1%) | 5 |
| Tachycardia | 1/70 (1.4%) | 1 |
| Low Ejection Fraction | 1/70 (1.4%) | 1 |
| Gastrointestinal disorders | ||
| Vomiting | 4/70 (5.7%) | 4 |
| Nausea | 61/70 (87.1%) | 61 |
| Diarrhea | 28/70 (40%) | 28 |
| Mucositis | 22/70 (31.4%) | 22 |
| Gastrointestinal Hemorrhage | 12/70 (17.1%) | 12 |
| General disorders | ||
| Fever | 21/70 (30%) | 21 |
| Fatigue | 6/70 (8.6%) | 6 |
| Rigors | 1/70 (1.4%) | 1 |
| Hepatobiliary disorders | ||
| Elevated ALT | 16/70 (22.9%) | 16 |
| Elevated Alkaline Phosphatase | 10/70 (14.3%) | 10 |
| Increased Bilirubin | 7/70 (10%) | 7 |
| Increased LDH | 1/70 (1.4%) | 1 |
| Infections and infestations | ||
| Infection | 37/70 (52.9%) | 88 |
| Metabolism and nutrition disorders | ||
| Hyperglycemia | 3/70 (4.3%) | 3 |
| Hypoglycemia | 1/70 (1.4%) | 1 |
| Hypocalcemia | 1/70 (1.4%) | 1 |
| Musculoskeletal and connective tissue disorders | ||
| Bone Pain | 5/70 (7.1%) | 5 |
| Nervous system disorders | ||
| Neuoropathy | 2/70 (2.9%) | 2 |
| Headache | 12/70 (17.1%) | 12 |
| Dizziness | 1/70 (1.4%) | 1 |
| Altered Mood | 3/70 (4.3%) | 3 |
| Insomnia | 3/70 (4.3%) | 3 |
| Pain | 5/70 (7.1%) | 5 |
| Altered Mood-Agitation | 1/70 (1.4%) | 1 |
| Anxiety | 1/70 (1.4%) | 1 |
| Renal and urinary disorders | ||
| Elevated Creatinine | 9/70 (12.9%) | 9 |
| Respiratory, thoracic and mediastinal disorders | ||
| Pneumonia | 10/70 (14.3%) | 10 |
| Pleural Effusion | 1/70 (1.4%) | 1 |
| Shortness of breath | 3/70 (4.3%) | 3 |
| Cough | 2/70 (2.9%) | 2 |
| Skin and subcutaneous tissue disorders | ||
| Skin rash | 32/70 (45.7%) | 32 |
| Skin Dryness | 1/70 (1.4%) | 1 |
| Fasciitis | 1/70 (1.4%) | 1 |
| pruritus | 1/70 (1.4%) | 1 |
Limitations/Caveats
More Information
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
| Name/Title | Issa Khouri, MD / Professor |
|---|---|
| Organization | UT MD Anderson Cancer Center |
| Phone | |
| rvalverde@mdanderson.org |
- ID01-233