Zevalin With Non Myeloablative Allogeneic Stem Cell Transplantation in Patients With Non Hodgkin Lymphoma
Primary Purpose
Non-Hodgkins Lymphoma
Status
Unknown status
Phase
Phase 1
Locations
Canada
Study Type
Interventional
Intervention
Rituximab
90Y ibritumomab tiuxetan (Zevalin)
Cyclophosphamide
Fludarabine
Non myeloablative allogeneic stem cell transplantation
Sponsored by
About this trial
This is an interventional treatment trial for Non-Hodgkins Lymphoma focused on measuring Allogeneic Stem Cell Transplantation, Zevalin, Non-Hodgkins Lymphoma
Eligibility Criteria
Inclusion Criteria:
Patients must have/be
- Age 18 to 65 years. Patients between age 66 and 69 may be enrolled if judged to be in excellent physical condition as per treating physician and study investigator and based on institutional practice.
- Diagnosis of Non-Hodgkin lymphoma, follicular, marginal zone, small lymphocytic lymphoma, mantle cell lymphoma or transformed from an indolent NHL to aggressive histology disease lymphoma as defined by the World Health Organization.
- Disease relapsed after, refractory or failing to achieve a PR after two or more cycles of intensive salvage chemotherapy (R-ESHAP or other) or disease relapsed after autologous stem cell transplantation. Poor partial response is defined as less than 50% reduction of tumor size. Salvage chemotherapy has to be administered after either 1st, 2nd or 3rd relapse
- Disease expressing the CD 20 antigen
- ECOG performance status 0-2
- Judged to be able to tolerate NST and Zevalin treatment based on institutional criteria.
- Signed written informed consent
- At least one fully HLA matched sibling without evident contraindications to the donation procedures and willing to sign consent for donation
Exclusion Criteria:
Patients must not have/be
- Abnormal renal function (creatinine > 1.5 x upper limit of normal (ULN)
- Abnormal hepatic function (bilirubin > 2 x ULN, ALT/AST>2x ULN)
- Cardiac ejection fraction <40% and/or other significant cardiac compromise
- Severe defects in pulmonary function tests or receiving continuous oxygen
- Severe concurrent illness, such as symptomatic congestive heart failure, severe arrhythmias, uncontrolled hypertension, diabetes, severe neurologic or psychiatric disorder or known HIV positive
- Previous or concurrent cancer that is distinct in primary site or histology from the cancer being evaluated except cervical carcinoma in situ, treated basal cell carcinoma, superficial bladder tumors (Ta, Tis & T1) that may impact on patients life expectancy or any cancer curatively treated < 3 years prior to study entry.
- History of prior allogeneic bone marrow transplant
- Evidence of active hepatitis B or C infection or positivity for hepatitis-B surface antigen
- Known type 1 hypersensitivity or anaphylactic proteins to any component of the Zevalin therapy or a history or presence of human anti-mouse antibodies (HAMA)
- A female patient who is pregnant or breast feeding and an adult of reproductive potential who is not employing an effective method of birth control during the study.
- CNS lymphoma
- Ongoing confirmed or suspected significant infection
- Prior treatment with radioimmunotherapy
- Other condition preventing participation in standard NST
- No fully matched sibling donor
Sites / Locations
- Hopital Maisonneuve-RosemontRecruiting
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
T
Arm Description
Outcomes
Primary Outcome Measures
Engraftment, chimerism, transplant related toxicity, acute and chronic GVHD
Secondary Outcome Measures
Overall response rate, overall and disease free survival
Full Information
NCT ID
NCT00807196
First Posted
December 10, 2008
Last Updated
December 10, 2008
Sponsor
Maisonneuve-Rosemont Hospital
Collaborators
Bayer
1. Study Identification
Unique Protocol Identification Number
NCT00807196
Brief Title
Zevalin With Non Myeloablative Allogeneic Stem Cell Transplantation in Patients With Non Hodgkin Lymphoma
Official Title
Phase I-II Non-Randomized Study of Yttrium 90 Ibritumomab Tiuxetan (Zevalin) With Non Myeloablative Allogeneic Stem Cell Transplantation in Patients With Relapsed, Refractory, or Transformed Indolent Non Hodgkin Lymphoma
Study Type
Interventional
2. Study Status
Record Verification Date
December 2008
Overall Recruitment Status
Unknown status
Study Start Date
September 2008 (undefined)
Primary Completion Date
December 2011 (Anticipated)
Study Completion Date
December 2012 (Anticipated)
3. Sponsor/Collaborators
Name of the Sponsor
Maisonneuve-Rosemont Hospital
Collaborators
Bayer
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The purpose of this study is to investigate the ability to combine a radioactive medication directly targeted against lymphoma cells with the immune effects of an allogeneic blood stem cell transplant.
Detailed Description
Despite initial high response rates of low grade Non Hodgkin lymphoma, progressive or refractory disease currently remains incurable. Being a radiosensitive tumor, we hypothesize that combining different modalities of treatment including targeted radioimmunotherapy (RIT), and a graft versus lymphoma effect related to an allogeneic non myeloablative stem cell transplant may increase response and survival rates in a safe manner in patients with persistent disease following initial treatment. In this study patients who are not eligible for a standard stem cell transplant approach because of relapsed or refractory disease and who have a related sibling donor are treated with RIT followed by an allogeneic non myeloablative blood stem cell transplant
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Non-Hodgkins Lymphoma
Keywords
Allogeneic Stem Cell Transplantation, Zevalin, Non-Hodgkins Lymphoma
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
20 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
T
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
Rituximab
Intervention Description
250mg/m2 day -21 and day -14 of preparative regimen
Intervention Type
Drug
Intervention Name(s)
90Y ibritumomab tiuxetan (Zevalin)
Intervention Description
0.4 mCi/kg IV on day -14 of preparative regimen
Intervention Type
Drug
Intervention Name(s)
Cyclophosphamide
Intervention Description
300mg/m2 IV daily for 5 days day -8 to day -4 of preparative regimen
Intervention Type
Drug
Intervention Name(s)
Fludarabine
Intervention Description
30mg/m2 IV daily for 5 days day -8 to day -4 of preparative regimen
Intervention Type
Other
Intervention Name(s)
Non myeloablative allogeneic stem cell transplantation
Intervention Description
Blood stem cell infusion on day 0
Primary Outcome Measure Information:
Title
Engraftment, chimerism, transplant related toxicity, acute and chronic GVHD
Time Frame
one year
Secondary Outcome Measure Information:
Title
Overall response rate, overall and disease free survival
Time Frame
360 days
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Patients must have/be
Age 18 to 65 years. Patients between age 66 and 69 may be enrolled if judged to be in excellent physical condition as per treating physician and study investigator and based on institutional practice.
Diagnosis of Non-Hodgkin lymphoma, follicular, marginal zone, small lymphocytic lymphoma, mantle cell lymphoma or transformed from an indolent NHL to aggressive histology disease lymphoma as defined by the World Health Organization.
Disease relapsed after, refractory or failing to achieve a PR after two or more cycles of intensive salvage chemotherapy (R-ESHAP or other) or disease relapsed after autologous stem cell transplantation. Poor partial response is defined as less than 50% reduction of tumor size. Salvage chemotherapy has to be administered after either 1st, 2nd or 3rd relapse
Disease expressing the CD 20 antigen
ECOG performance status 0-2
Judged to be able to tolerate NST and Zevalin treatment based on institutional criteria.
Signed written informed consent
At least one fully HLA matched sibling without evident contraindications to the donation procedures and willing to sign consent for donation
Exclusion Criteria:
Patients must not have/be
Abnormal renal function (creatinine > 1.5 x upper limit of normal (ULN)
Abnormal hepatic function (bilirubin > 2 x ULN, ALT/AST>2x ULN)
Cardiac ejection fraction <40% and/or other significant cardiac compromise
Severe defects in pulmonary function tests or receiving continuous oxygen
Severe concurrent illness, such as symptomatic congestive heart failure, severe arrhythmias, uncontrolled hypertension, diabetes, severe neurologic or psychiatric disorder or known HIV positive
Previous or concurrent cancer that is distinct in primary site or histology from the cancer being evaluated except cervical carcinoma in situ, treated basal cell carcinoma, superficial bladder tumors (Ta, Tis & T1) that may impact on patients life expectancy or any cancer curatively treated < 3 years prior to study entry.
History of prior allogeneic bone marrow transplant
Evidence of active hepatitis B or C infection or positivity for hepatitis-B surface antigen
Known type 1 hypersensitivity or anaphylactic proteins to any component of the Zevalin therapy or a history or presence of human anti-mouse antibodies (HAMA)
A female patient who is pregnant or breast feeding and an adult of reproductive potential who is not employing an effective method of birth control during the study.
CNS lymphoma
Ongoing confirmed or suspected significant infection
Prior treatment with radioimmunotherapy
Other condition preventing participation in standard NST
No fully matched sibling donor
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Thomas Kiss, MD
Phone
514-252-3404
Email
thomas.kiss@umomtreal.ca
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Thomas Kiss, MD
Organizational Affiliation
Maisonneuve-Rosemont Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Hopital Maisonneuve-Rosemont
City
Montreal
State/Province
Quebec
ZIP/Postal Code
H2V 1W7
Country
Canada
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Thomas Kiss, MD
Phone
(514)252-3404
Email
thomas.kiss@umontreal.ca
First Name & Middle Initial & Last Name & Degree
Dominique Beaupré, BSc nursing
Phone
(514)252-3400
Ext
5605
Email
dbeaupré.hmr@ssss.gouv.qc.ca
First Name & Middle Initial & Last Name & Degree
Thomas Kiss, M.D.
12. IPD Sharing Statement
Learn more about this trial
Zevalin With Non Myeloablative Allogeneic Stem Cell Transplantation in Patients With Non Hodgkin Lymphoma
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