Yttrium Y 90 Ibritumomab Tiuxetan, Fludarabine, Radiation Therapy, and Donor Stem Cell Transplant in Treating Patients With Relapsed or Refractory Non-Hodgkin's Lymphoma - Full Text View

Sponsored by:	Fred Hutchinson Cancer Research Center
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00119392

Purpose

RATIONALE: Monoclonal antibodies, such as rituximab and yttrium Y 90 Ibritumomab tiuxetan, can find cancer cells and carry cancer-killing substances to them without harming normal cells. Giving monoclonal antibodies, low doses of chemotherapy, such as fludarabine, and radiation therapy before a donor peripheral stem cell transplant helps stop the growth of cancer cells and also stops the patient's immune system from rejecting the donor's stem cells.

The donated stem cells may replace the patient's immune system and help destroy any remaining cancer cells (graft-versus-tumor effect). Sometimes the transplanted cells from a donor can also make an immune response against the body's normal cells. Giving cyclosporine or mycophenolate mofetil after the transplant may stop this from happening.

PURPOSE: This phase II trial is studying how well giving yttrium Y 90 ibritumomab tiuxetan together with fludarabine, radiation therapy, and donor stem cell transplant works in treating patients with relapsed or refractory B-cell non-Hodgkin's lymphoma.

Condition	Intervention	Phase
Lymphoma	Biological: rituximab Drug: cyclosporine Drug: fludarabine phosphate Drug: mycophenolate mofetil Procedure: peripheral blood stem cell transplantation Radiation: radiation therapy Radiation: yttrium Y 90 ibritumomab tiuxetan	Phase II

Study Type:	Interventional
Study Design:	Treatment, Open Label
Official Title:	A Phase II Trial Evaluating the Safety and Efficacy of Non-Myeloablative Y-Ibritumomab Tiuxetan (Anti-CD20) Antibody With Fludarabine, Low-Dose Total Body Irradiation (TBI) and HLA Matched Allogeneic Transplantation for Relapsed B-Cell Lymphoma

Resource links provided by NLM:

MedlinePlus related topics: Cancer Lymphoma Radiation Therapy

Drug Information available for: Fludarabine Cyclosporine Fludarabine monophosphate Cyclosporin Mycophenolate mofetil hydrochloride Mycophenolate Mofetil Rituximab Ibritumomab tiuxetan

U.S. FDA Resources

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Treatment-related mortality at day 100 [ Designated as safety issue: No ]

Estimated Enrollment:	40
Study Start Date:	June 2004
Estimated Primary Completion Date:	June 2070 (Final data collection date for primary outcome measure)

Detailed Description:

OBJECTIVES:

Primary

Determine the feasibility and safety of a nonmyeloablative conditioning regimen comprising yttrium Y 90 ibritumomab tiuxetan, fludarabine, and low-dose total-body irradiation followed by allogeneic peripheral blood stem cell transplantation in patients with relapsed or refractory B-cell non-Hodgkin's lymphoma.
Determine the 100-day treatment-related mortality in patients treated with this regimen.

Secondary

Determine the potential efficacy of this regimen in these patients.
Determine overall and progression-free survival of patients treated with this regimen.
Determine the response rate, including molecular response, in patients treated with this regimen.
Determine engraftment and hematopoietic adverse events in patients treated with this regimen.
Determine the incidence and severity of acute and chronic graft-versus-host disease in patients treated with this regimen.

OUTLINE:

Conditioning regimen: Patients receive rituximab IV followed, no more than 4 hours later, by indium In 111 ibritumomab tiuxetan (for imaging) IV over 10 minutes on day -21. Patients undergo gamma camera imaging on days
- 21, -19, and -18. If biodistribution is acceptable, patients receive rituximab IV followed, no more than 4 hours later, by yttrium Y 90 ibritumomab tiuxetan IV over 10 minutes on day -14. Patients also receive fludarabine IV over 30-60 minutes on days -7 to -5 and undergo low-dose total-body irradiation (TBI) on day 0.
Allogeneic peripheral blood stem cell transplantation (PBSCT): After TBI, patients undergo allogeneic PBSCT on day 0.
Immunosuppression: Patients who undergo PBSCT from a related donor receive oral cyclosporine twice daily on days -3 to 56 followed by a taper to day 180 in the absence of graft-versus-host disease (GVHD). These patients also receive oral mycophenolate mofetil twice daily on days 0-27. Patients who undergo PBSCT from an unrelated donor receive oral cyclosporine twice daily on days -3 to 100 followed by a taper over 11 weeks in the absence of GVHD. These patients also receive oral mycophenolate mofetil three times daily on days 0-40 followed by a taper to day 96. After completion of study treatment, patients are followed at 1, 3, 6, and 12 months, and then annually thereafter.

PROJECTED ACCRUAL: A total of 40 patients will be accrued for this study within 4 years.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

DISEASE CHARACTERISTICS:

Histologically confirmed B-cell non-Hodgkin's lymphoma
- Relapsed or refractory disease
  - Failed ≥ 1 prior standard systemic therapy
CD20 antigen-positive disease
Evidence of persistent disease by physical examination, radiographic studies, bone marrow evaluation, flow cytometry, or polymerase chain reaction
No CNS lymphoma
Not eligible for a radioimmunotherapy-based autologous stem cell transplantation trial
Not eligible for other therapeutic options (e.g., non-transplantation therapy or autologous stem cell transplantation) likely to have a better long-term disease-free survival with lower potential toxicity than this study
No progressive disease within the past 3 months due to prior tositumomab or ibritumomab tiuxetan
HLA-matched identical related or unrelated donor available
- Related donor matched for HLA-A, -B, -C, and -DRB1 and to the allele level of DQB1
  - No identical twins
- Unrelated donor matched for HLA-A, -B, -C, -DRB1, and -DQB1
  - One allele mismatch for HLA-A, -B, or -C allowed

PATIENT CHARACTERISTICS:

Age

18 and over

Performance status

SWOG 0-2 OR
ECOG 0-2

Life expectancy

More than 60 days

Hematopoietic

Not specified

Hepatic

Bilirubin < 1.5 mg/dL

Renal

Creatinine < 2.0 mg/dL

Cardiovascular

No unstable angina

Pulmonary

DLCO ≥ 30%
Total lung capacity ≥ 30%
No requirement for continuous supplemental oxygen

Other

Must be able to understand and give informed consent
Not pregnant or nursing
Fertile patients must use effective contraception during and for 12 months after completion of study treatment
HIV negative
No AIDS
No major infection
No other serious medical condition that would preclude allogeneic stem cell transplantation
No evidence of human antimouse antibody for patients previously exposed to therapeutic murine antibodies

PRIOR CONCURRENT THERAPY:

Biologic therapy

Not specified

Chemotherapy

Not specified

Endocrine therapy

Not specified

Radiotherapy

Not specified

Surgery

Not specified

Other

More than 30 days since prior systemic anti-lymphoma therapy

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00119392

Locations

United States, Washington
Fred Hutchinson Cancer Research Center
Seattle, Washington, United States, 98109-1024

Sponsors and Collaborators

Fred Hutchinson Cancer Research Center

Investigators

Principal Investigator:

Ajay K. Gopal, MD

Fred Hutchinson Cancer Research Center

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	Fred Hutchinson Cancer Research Center ( Ajay K. Gopal )
Study ID Numbers:	CDR0000430649, FHCRC-1726.00
Study First Received:	July 12, 2005
Last Updated:	April 23, 2009
ClinicalTrials.gov Identifier:	NCT00119392 History of Changes
Health Authority:	United States: Federal Government

Keywords provided by National Cancer Institute (NCI):

recurrent adult Burkitt lymphoma
recurrent adult diffuse large cell lymphoma
recurrent adult diffuse mixed cell lymphoma
recurrent adult diffuse small cleaved cell lymphoma
recurrent adult immunoblastic large cell lymphoma
recurrent adult lymphoblastic lymphoma
recurrent grade 1 follicular lymphoma

recurrent grade 2 follicular lymphoma
recurrent grade 3 follicular lymphoma
recurrent mantle cell lymphoma
recurrent marginal zone lymphoma
extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue
nodal marginal zone B-cell lymphoma
splenic marginal zone lymphoma

Study placed in the following topic categories:

Antimetabolites
Anti-Infective Agents
Cyclosporine
Immunologic Factors
Lymphoma, Mantle-Cell
Lymphoma, Follicular
Lymphoma, B-Cell, Marginal Zone
Mantle Cell Lymphoma
Cyclosporins
Follicular Lymphoma
Lymphoblastic Lymphoma
Lymphoma, Large-cell, Immunoblastic
Antibodies, Monoclonal
Lymphoma, B-Cell
Lymphoma, Small Cleaved-cell, Diffuse

Antifungal Agents
Lymphoma, Large-Cell, Immunoblastic
Mycophenolate mofetil
Lymphoma, Large-cell
Lymphoma
Immunoglobulins
Lymphoma, Large B-Cell, Diffuse
Immunoproliferative Disorders
Rituximab
Fludarabine monophosphate
Immunosuppressive Agents
Recurrence
Lymphatic Diseases
Burkitt's Lymphoma
Antibodies

Additional relevant MeSH terms:

Antimetabolites
Anti-Infective Agents
Antimetabolites, Antineoplastic
Cyclosporine
Molecular Mechanisms of Pharmacological Action
Immunologic Factors
Antineoplastic Agents
Physiological Effects of Drugs
Cyclosporins
Lymphoma, B-Cell
Antibodies, Monoclonal
Antifungal Agents
Therapeutic Uses
Mycophenolate mofetil
Lymphoma

Dermatologic Agents
Immunoproliferative Disorders
Neoplasms by Histologic Type
Immune System Diseases
Enzyme Inhibitors
Fludarabine monophosphate
Immunosuppressive Agents
Pharmacologic Actions
Lymphatic Diseases
Neoplasms
Fludarabine
Antirheumatic Agents
Lymphoma, Non-Hodgkin
Lymphoproliferative Disorders

ClinicalTrials.gov processed this record on September 09, 2009