Radioimmunotherapy With 90Y-ibritumomab Tiuxetan as Part of a Dose Reduced Conditioning Regimen for Allogeneic Hematopoietic Cell Transplantation for the Treatment of Non-Hodgkin Lymphoma

Sponsor

University Hospital Tuebingen (Other)

Overall Status

Completed

CT.gov ID

NCT00302757

Collaborator

(none)

Enrollment

Locations

Duration (Months)

5.5

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The study evaluates the additional use of radioimmunotherapy with a 90-Yttrium labeled monoclonal antibody targeting lymphoma cells in two dose reduced conditioning regimens for allogeneic hematopoietic cell transplantation from human leukocyte antigen (HLA)-identical donors. Radioimmunotherapy should allow an increased anti-lymphoma effect of the conditioning while the allogeneic grafts may confer potent graft versus lymphoma effects and rescue from potential hematopoietic side effects of the radioimmunotherapy. The study evaluates the feasibility and toxicity of such approach and will also analyze disease response and survival of the patients treated.

Condition or Disease	Intervention/Treatment	Phase
Non-Hodgkin Lymphoma	Drug: Radioimmunotherapy Procedure: allogeneic hematopoietic cell transplantation	Phase 1/Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

60 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Multicenter Phase I/II Study of Radioimmunotherapy With 90Y-ibritumomab Tiuxetan in a Nonmyeloablative Conditioning Regimen for Allogeneic Hematopoietic Cell Transplantation From HLA-identical Donors in Patients With Advanced Non-Hodgkin Lymphoma

Study Start Date :

Mar 1, 2006

Actual Study Completion Date :

Jul 1, 2011

Outcome Measures

Primary Outcome Measures

treatment related toxicity []
engraftment []

Secondary Outcome Measures

disease response []
relapse rate []
disease free survival []
overall survival []
graft versus host disease (GVHD) []
immunoreconstitution []

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 70 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Patients with advanced CD20+ NHL (non-Hodgkin lymphoma) relapsed after at least two preceding chemotherapy regimens including treatment with rituximab or with relapse after autologous HCT (hematopoietic cell transplantation)

The following entities of lymphomas can be included in Arm A of the protocol:

Arm A:

Small lymphocytic lymphoma (SLL/CLL)
Mantle cell lymphoma (MCL)
Follicular lymphoma Grade 1-2
Marginal zone lymphoma (MZL)
Extranodal (MALT lymphoma)
Nodal (Monocytoid B-cell lymphoma)
Splenic

The following lymphoma entities can be included in Arm B of the protocol:

Arm B:

Diffuse large B-cell lymphoma/follicular lymphoma grade 3
Grade 3 follicular lymphoma
Blastic mantle cell lymphoma
Mediastinal B-cell lymphoma
Age > 18, < 70 years
Karnofsky score > 60%
HLA-identical related or unrelated donor
CD20+ lymphoma cells on biopsy or peripheral blood
Disease stage at inclusion: CR, PR or SD

Exclusion Criteria:

Patients with rapidly progressive disease
Less than 3 months after preceding HCT
CNS involvement with disease
Fungal infections with radiological progression after receipt of amphotericin B or active triazole for greater than 1 month
Liver function abnormalities with bilirubin > 2 mg/dL and elevation of transaminases higher than 2x upper limit of normal
Chronic active viral hepatitis
Ejection fraction < 40% on echocardiography
Patients with > grade II hypertension by CTC criteria
Creatinine clearance < 50 ml/min
Respiratory failure necessitating supplemental oxygen or DLCO < 30%
Allergy against murine antibodies
HIV infection
Female patients who are pregnant or breast feeding, or adults of reproductive potential not employing an effective method of birth control during study treatment and for at least 12 months thereafter. (Women of childbearing potential must have a negative serum pregnancy test at study entry.)
Patients with pleural effusion or ascites
Concurrent severe and/or uncontrolled medical disease (e.g. uncontrolled diabetes, congestive heart failure, myocardial infarction within 6 months prior to the study, unstable and uncontrolled hypertension, chronic renal disease, or active uncontrolled infection) which could compromise participation in the study
Patients who received any investigational drugs less than 4 weeks before entry in this study or who have not as yet recovered from the toxic effects of such therapy
Patients who underwent surgery within 4 weeks of entering the study or patients who have not as yet recovered from the side-effects of such treatment
Patients with a history of psychiatric illness or condition which could interfere with their ability to understand the requirements of the study (this includes alcoholism/drug addiction)
Patients unwilling or unable to comply with the protocol
Unable to give informed consent
Enrollment in another trial interfering with the endpoints of this study

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	Medical Center Charite Benjamin Franklin	Berlin	Germany	12200
2	University of Dresden Medical Center	Dresden	Germany	D-01307
3	Center for Marrow Transplantation, University of Essen	Essen	Germany	45122
4	Medical Center University of Goettingen	Goettingen	Germany	37099
5	Medical Center University of Hannover	Hannover	Germany	30625
6	Medical Center University of Leipzig	Leipzig	Germany	04103
7	Medical Center University of Muenster	Muenster	Germany	48149
8	South West German Cancer Center, University of Tuebingen Medical Center	Tuebingen	Germany	72076
9	Medical Center University of Ulm	Ulm	Germany	89081
10	Stiftung Deutsche Klinik für Diagnostik GmbH	Wiesbaden	Germany	65191
11	University of Wuerzburg Medical Center	Wuerzburg	Germany	D-97070

Sponsors and Collaborators

University Hospital Tuebingen

Investigators

Principal Investigator: Wolfgang A Bethge, MD, Medical Center University of Tuebingen
Principal Investigator: Donald Bunjes, MD, Medical Center University of Ulm