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

University Hospital Tuebingen

Status and phase

Completed

Phase 2

Phase 1

Conditions

Non-Hodgkin Lymphoma

Treatments

Drug: Radioimmunotherapy

Procedure: allogeneic hematopoietic cell transplantation

Study type

Interventional

Funder types

Other

Identifiers

NCT00302757

2005-002206-37

Details and patient eligibility

About

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.

Enrollment

60 estimated patients

Sex

All

Ages

18 to 70 years old

Volunteers

No 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