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Safety and Efficacy of 90Y Zevalin in Nonmyeloablative Transplantation for Lymphoid Malignancies
This study is currently recruiting participants.
Verified by M.D. Anderson Cancer Center, October 2008
Sponsors and Collaborators: M.D. Anderson Cancer Center
Biogen Idec
Information provided by: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT00048737
  Purpose

This is a phase I/II study to determine the safety and efficacy of nonmyeloablative allogeneic stem cell transplantation using 90Y Zevalin/Cyclophosphamide/Fludarabine as a preparative regimen for patients with B-cell lymphoid malignancies.


Condition Intervention Phase
Lymphoma
Leukemia
Drug: Zevalin Radioimmunotherapy
Drug: Rituximab
Drug: Fludarabine
Drug: Cyclophosphamide
Procedure: Allogeneic Stem Cell Transplantation
Phase I
Phase II

MedlinePlus related topics: Cancer Leukemia, Adult Acute Leukemia, Adult Chronic Lymphoma
Drug Information available for: Cyclophosphamide Fludarabine Fludarabine monophosphate Rituximab Ibritumomab tiuxetan
U.S. FDA Resources
Study Type: Interventional
Study Design: Treatment, Non-Randomized, Open Label, Uncontrolled, Single Group Assignment, Safety/Efficacy Study
Official Title: Safety and Efficacy of 90Y Zevalin in Nonmyeloablative Transplantation for Lymphoid Malignancies

Further study details as provided by M.D. Anderson Cancer Center:

Primary Outcome Measures:
  • Determine the safety of nonmyeloablative allogeneic stem cell transplantation using 90Y Zevalin/Cyclophosphamide/Fludarabine as a preparative regimen for patients with B-cell lymphoid malignancies. [ Time Frame: 6 Years ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Determine the efficacy of nonmyeloablative allogeneic stem cell transplantation using 90Y Zevalin/Cyclophosphamide/Fludarabine as a preparative regimen for patients with B-cell lymphoid malignancies. [ Time Frame: 6 Years ] [ Designated as safety issue: No ]

Estimated Enrollment: 30
Study Start Date: October 2002
Estimated Primary Completion Date: December 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
1: Experimental
Allogeneic Stem Cell 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
Drug: Rituximab
250 mg/m^2 on day 1 and day 8
Drug: Fludarabine
30 mg/m^2/day x 3
Drug: Cyclophosphamide
750 mg/m^2/day x 3, given on the same days as fludarabine, at 4-hour intervals
Procedure: Allogeneic Stem Cell Transplantation
Allogeneic stem cell transplantation 2 days after chemotherapy

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, 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. G-CSF, 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.

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion:

  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 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.

Exclusion:

  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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00048737

Contacts
Contact: Issa F. Khouri, MD 713-745-2803

Locations
United States, Texas
MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Principal Investigator: Issa Khouri, MD            
Sponsors and Collaborators
M.D. Anderson Cancer Center
Biogen Idec
Investigators
Principal Investigator: Issa F. Khouri, MD U.T.M.D. Anderson Cancer Center
  More Information

The University of Texas M.D.Anderson Cancer Center  This link exits the ClinicalTrials.gov site

Responsible Party: U.T. M.D. Anderson Cancer Center ( Issa F. Khouri, MD/Professor )
Study ID Numbers: ID01-233
Study First Received: November 6, 2002
Last Updated: October 10, 2008
ClinicalTrials.gov Identifier: NCT00048737  
Health Authority: United States: Food and Drug Administration

Keywords provided by M.D. Anderson Cancer Center:
Leukemia
Lymphoma
Lymphoid Malignancy
Cyclophosphamide
Fludarabine
Rituximab
Zevalin
CD-20-positive
B-cell Lymphoma
CD-20-positive B-cell Lymphoma
NHL
CLL
Chronic Lymphocytic Leukemia
Allogeneic Stem Cell Transplantation

Study placed in the following topic categories:
Chronic lymphocytic leukemia
Leukemia, Lymphoid
Immunoproliferative Disorders
Rituximab
Leukemia, B-cell, chronic
Cyclophosphamide
Fludarabine monophosphate
Lymphoma, B-Cell
Leukemia
Lymphatic Diseases
Leukemia, Lymphocytic, Chronic, B-Cell
B-cell lymphomas
Fludarabine
Lymphoproliferative Disorders
Lymphoma

Additional relevant MeSH terms:
Antimetabolites
Antimetabolites, Antineoplastic
Neoplasms by Histologic Type
Immune System Diseases
Immunologic Factors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Physiological Effects of Drugs
Immunosuppressive Agents
Pharmacologic Actions
Neoplasms
Therapeutic Uses
Myeloablative Agonists
Antineoplastic Agents, Alkylating
Antirheumatic Agents
Alkylating Agents

ClinicalTrials.gov processed this record on January 15, 2009