Clinical trial NCT00302757: 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
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Non-Hodgkin Lymphoma
Keywords: NHL
low and high grade non-Hodgkin lymphoma
Lead sponsor: University Hospital Tuebingen
Sponsor class: OTHER
First posted: 2006-03-14
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: treatment related toxicity
measure: engraftment
Secondary outcomes:
measure: disease response
measure: relapse rate
measure: disease free survival
measure: overall survival
measure: graft versus host disease (GVHD)
measure: immunoreconstitution
Other outcomes:
Locations:
city: Berlin
country: Germany
facility: Medical Center Charite Benjamin Franklin
city: Dresden
country: Germany
facility: University of Dresden Medical Center
city: Essen
country: Germany
facility: Center for Marrow Transplantation, University of Essen
city: Goettingen
country: Germany
facility: Medical Center University of Goettingen
city: Hannover
country: Germany
facility: Medical Center University of Hannover
city: Leipzig
country: Germany
facility: Medical Center University of Leipzig
city: Muenster
country: Germany
facility: Medical Center University of Muenster
city: Tuebingen
country: Germany
facility: South West German Cancer Center, University of Tuebingen Medical Center
city: Ulm
country: Germany
facility: Medical Center University of Ulm
city: Wiesbaden
country: Germany
facility: Stiftung Deutsche Klinik für Diagnostik GmbH
city: Wuerzburg
country: Germany
facility: University of Wuerzburg Medical Center
Study officials:
affiliation: Medical Center University of Tuebingen
name: Wolfgang A Bethge, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Medical Center University of Ulm
name: Donald Bunjes, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Bethge WA, von Harsdorf S, Bornhauser M, Federmann B, Stelljes M, Trenschel R, Baurmann H, Dittmann H, Faul C, Vogel W, Kanz L, Bunjes D. Dose-escalated radioimmunotherapy as part of reduced intensity conditioning for allogeneic transplantation in patients with advanced high-grade non-Hodgkin lymphoma. Bone Marrow Transplant. 2012 Nov;47(11):1397-402. doi: 10.1038/bmt.2012.62. Epub 2012 Apr 16.
citation: Bethge WA, Lange T, Meisner C, von Harsdorf S, Bornhaeuser M, Federmann B, Stadler M, Uharek L, Stelljes M, Knop S, Wulf G, Trenschel R, Vucinic V, Dittmann H, Faul C, Vogel W, Kanz L, Bunjes D. Radioimmunotherapy with yttrium-90-ibritumomab tiuxetan as part of a reduced- intensity conditioning regimen for allogeneic hematopoietic cell transplantation in patients with advanced non-Hodgkin lymphoma: results of a phase 2 study. Blood. 2010 Sep 9;116(10):1795-802. doi: 10.1182/blood-2010-02-270538. Epub 2010 Jun 7.