Ignite Creation Date:
2024-05-05 @ 4:36 PM
Last Modification Date:
2024-10-26 @ 9:21 AM
Study NCT ID:
NCT00271050
Status:
COMPLETED
Last Update Posted:
2010-12-21
First Post:
2005-12-28
Brief Title:
External Beam Radiotherapy and Zevalin for Management of Indolent B-Cell Non-Hodgkins Lymphoma
Sponsor:
The Cleveland Clinic
Organization:
The Cleveland Clinic
Study Overview
Official Title:
The Role of Conformal External Beam Radiotherapy in the Management of Patients With Bulky Disease Undergoing Y90-Ibritumomab Tiuxetan Zevalin Radio-immunotherapy for Indolent B-cell Non-Hodgkins Lymphoma
Status:
COMPLETED
Status Verified Date:
2010-12
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
The purpose of the research study is to learn whether external beam radiation can be used as a safe and effective treatment for patients with bulky 5cm sites of non-Hodgkins lymphoma prior to treatment with 90Y-ibritumomab tiuxetan Zevalin
Detailed Description:
Non-Hodgkins lymphomas NHL are a heterogeneous group of lymphoid malignancies that represent the 6th leading cause of cancer death and the 2nd fastest growing cancer in the United States NHLs can be divided into two prognostic groups aggressive and indolent lymphomas Aggressive NHLs grow rapidly and present as disseminated disease in 70 of cases yet can be cured in a significant number of patients with intensive combination chemotherapy regimens Indolent low-grade NHLs are slow growing malignancies with long natural histories that are incurable when disseminated Early stage low-grade NHL stage I and II has the potential for cure with radiotherapy but only 10-20 of patients with low-grade NHL present with early stage disease The vast majority of patients with low-grade NHL present with advanced disseminated disease While indolent B-cell NHLs have initial sensitivity to chemotherapy and radiotherapy they frequently relapse and become increasingly resistant to therapy with each successive relapse eventually transforming to aggressive lymphomas in most patients Fifty percent of patients presenting with advanced indolent NHL die within 5 years of their first relapse Only modest improvement has been made in the last 25 years in increasing the survival of patients with indolent NHL with current median survival of 7-10 years
Recent advances in the field of immunotherapy have proved to benefit patients with relapsed or refractory B-cell NHL In 1997 rituximab became the first FDA-approved monoclonal antibody mAb for the treatment of cancer Rituximab a chimeric IgG1 kappa monoclonal antibody specifically recognizes and binds to the CD20 antigen found on the cell surface of most normal B-cells and malignant B-cell lymphomas Rituximab binds human complement and lyses B-cell lines through complement dependent cytotoxicity and antibody dependent cellular toxicity A multi-center Phase II trial of 166 patients with relapsed indolent B-cell lymphoma treated with rituximab found an overall response in 50 of patients with 6 having a complete response and 44 having a partial response Time to progression was a median of 13 months in patients who responded
The introduction of radioimmunotherapy RIT has exploited the tumor cell targeting ability of mAbs to deliver doses of radiation to the tumor and limited surrounding tissue This is especially useful in the treatment of NHL because lymphomas are highly sensitive to radiotherapy 90Yttrium-ibritumomab tiuxetan Zevalin is a unique compound composed of the murine IgG1 anti-CD20 antibody ibritumomab the linker chelator tiuxetan and the radioisotope 90Y chelated via the linker 90Y-ibritumomab tiuxetan can be described as providing a double hit therapeutic approach by having the CD20 antibody properties of rituximab combined with radiation therapy
90Yttrium-ibritumomab tiuxetan appears to be effective in the treatment of patients refractory to treatment with rituximab but response rates decrease with increasing tumor size 90Y-ibritumomab tiuxetan was approved by the FDA in 2002 for the treatment of patients with relapsed or refractory low-grade follicular or CD20 transformed B-cell non-Hodgkins lymphoma NHL and rituximab-refractory follicular NHL
A preliminary survey of 20 patients treated with 90Y-ibritumomab tiuxetan at the Cleveland Clinic Foundation from 1998-2003 detailed patterns of NHL recurrence after treatment The results of this survey were presented in part by Dr Macklis at the 2004 annual meeting of the American Society of Therapeutic Radiation Oncology ASTRO in Atlanta and recently accepted for publication in the International Journal of Radiation Oncology Biology Physics Based on preliminary data a hypothesis can be made that some likely sites of disease recurrenceprogression after RIT can be predicted by the volume of disease at a specific site prior to RIT In short pre-RIT bulky sites of disease are the most likely locations of disease recurrence after RIT followed by gross but non-bulky pre-RIT sites followed by entirely new sites Based on this hypothesis it might be beneficial to pre-treat bulky sites of NHL with external beam radiotherapy prior to RIT in order to promote a more durable response Doses of external beam radiation required to consolidate these bulky disease sites are unclear
In this study we plan to utilize a dose of EBRT of 2400cGy to bulky sites of disease followed by RIT Though the combined effects of 2400cGy of EBRT and RIT are likely to be well tolerated such a combination has not been sufficiently studied Therefore the primary goal of this study is to determine if the combination of EBRT and RIT has an acceptable toxicity profile with regard to long-term myelosuppression and other non-hematological toxicities
Recent advances in the field of immunotherapy have proved to benefit patients with relapsed or refractory B-cell NHL In 1997 rituximab became the first FDA-approved monoclonal antibody mAb for the treatment of cancer Rituximab a chimeric IgG1 kappa monoclonal antibody specifically recognizes and binds to the CD20 antigen found on the cell surface of most normal B-cells and malignant B-cell lymphomas Rituximab binds human complement and lyses B-cell lines through complement dependent cytotoxicity and antibody dependent cellular toxicity A multi-center Phase II trial of 166 patients with relapsed indolent B-cell lymphoma treated with rituximab found an overall response in 50 of patients with 6 having a complete response and 44 having a partial response Time to progression was a median of 13 months in patients who responded
The introduction of radioimmunotherapy RIT has exploited the tumor cell targeting ability of mAbs to deliver doses of radiation to the tumor and limited surrounding tissue This is especially useful in the treatment of NHL because lymphomas are highly sensitive to radiotherapy 90Yttrium-ibritumomab tiuxetan Zevalin is a unique compound composed of the murine IgG1 anti-CD20 antibody ibritumomab the linker chelator tiuxetan and the radioisotope 90Y chelated via the linker 90Y-ibritumomab tiuxetan can be described as providing a double hit therapeutic approach by having the CD20 antibody properties of rituximab combined with radiation therapy
90Yttrium-ibritumomab tiuxetan appears to be effective in the treatment of patients refractory to treatment with rituximab but response rates decrease with increasing tumor size 90Y-ibritumomab tiuxetan was approved by the FDA in 2002 for the treatment of patients with relapsed or refractory low-grade follicular or CD20 transformed B-cell non-Hodgkins lymphoma NHL and rituximab-refractory follicular NHL
A preliminary survey of 20 patients treated with 90Y-ibritumomab tiuxetan at the Cleveland Clinic Foundation from 1998-2003 detailed patterns of NHL recurrence after treatment The results of this survey were presented in part by Dr Macklis at the 2004 annual meeting of the American Society of Therapeutic Radiation Oncology ASTRO in Atlanta and recently accepted for publication in the International Journal of Radiation Oncology Biology Physics Based on preliminary data a hypothesis can be made that some likely sites of disease recurrenceprogression after RIT can be predicted by the volume of disease at a specific site prior to RIT In short pre-RIT bulky sites of disease are the most likely locations of disease recurrence after RIT followed by gross but non-bulky pre-RIT sites followed by entirely new sites Based on this hypothesis it might be beneficial to pre-treat bulky sites of NHL with external beam radiotherapy prior to RIT in order to promote a more durable response Doses of external beam radiation required to consolidate these bulky disease sites are unclear
In this study we plan to utilize a dose of EBRT of 2400cGy to bulky sites of disease followed by RIT Though the combined effects of 2400cGy of EBRT and RIT are likely to be well tolerated such a combination has not been sufficiently studied Therefore the primary goal of this study is to determine if the combination of EBRT and RIT has an acceptable toxicity profile with regard to long-term myelosuppression and other non-hematological toxicities
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| CCF IRB 7883 | None | None | None |
| Case 1405 | None | None | None |