Safety and Efficacy of 90Y Zevalin in Nonmyeloablative Transplantation for Lymphoid Malignancies

Lymphoma Clinical Trial

Official title:

Safety and Efficacy of 90Y Zevalin in Nonmyeloablative Transplantation for Lymphoid Malignancies

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00048737
• Other study ID #: ID01-233
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: November 6, 2002
• Last updated: June 11, 2013
• Start date: October 2002
• Est. completion date: December 2011

Study information

• Verified date: June 2013
• Source: M.D. Anderson Cancer Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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 The bone marrow is then withdrawn through the needle.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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 70
• Est. completion date: December 2011
• Est. primary completion date: December 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria:

1. 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.

2. Measurable disease.

3. Age 18-70 years, expected survival >/= 3 months, performance status 0 to 2.

4. Availability of a matched related donor.

5. </+ 50% bone marrow involvement.

6. CLL with </+ 10,000 circulating lymphocytes.

7. Availability of a matched related or unrelated donor.

Exclusion Criteria:

1. Prior myeloablative therapies or radioimmunotherapy.

2. Prior external beam radiation therapy to >25% of active bone marrow.

3. Prior therapy with 90Y Zevalin or Campath.

4. CNS lymphoma, HIV, HTLV-1 positivity, some creatinine >1.6 mg/dl or serum bilirubin >1.5 mg/dl.

5. Pregnancy or lactation.

6. Symptomatic pulmonary or cardiac disease.

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Leukemia
• Lymphoma

Intervention

Drug:
• Zevalin Radioimmunotherapy
Escalating single dose of 90Y Zevalin 0.2-0.3-0.4 mCi/kg
• Rituximab
250 mg/m^2 on day 1 and day 8
• Fludarabine
30 mg/m^2/day for 3 days
• Cyclophosphamide
750 mg/m^2/day for 3 days, given on the same days as fludarabine, at 4-hour intervals

Procedure:
• Allogeneic Stem Cell Transplantation
Allogeneic stem cell transplantation 2 days after chemotherapy

Locations

Country	Name	City	State
United States	MD Anderson Cancer Center	Houston	Texas

Sponsors (2)

Lead Sponsor	Collaborator
M.D. Anderson Cancer Center	Biogen

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	100 days	Yes

External Links

•   The University of Texas M.D.Anderson Cancer Center official website