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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

Primary Purpose

Non-Hodgkin Lymphoma

Status
Completed
Phase
Phase 1
Locations
Germany
Study Type
Interventional
Intervention
Radioimmunotherapy
allogeneic hematopoietic cell transplantation
Sponsored by
University Hospital Tuebingen
About
Eligibility
Locations
Outcomes
Full info

About this trial

This is an interventional treatment trial for Non-Hodgkin Lymphoma focused on measuring NHL, low and high grade non-Hodgkin lymphoma

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept 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

Sites / Locations

  • Medical Center Charite Benjamin Franklin
  • University of Dresden Medical Center
  • Center for Marrow Transplantation, University of Essen
  • Medical Center University of Goettingen
  • Medical Center University of Hannover
  • Medical Center University of Leipzig
  • Medical Center University of Muenster
  • South West German Cancer Center, University of Tuebingen Medical Center
  • Medical Center University of Ulm
  • Stiftung Deutsche Klinik für Diagnostik GmbH
  • University of Wuerzburg Medical Center

Outcomes

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

Full Information

First Posted
March 10, 2006
Last Updated
May 28, 2014
Sponsor
University Hospital Tuebingen
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1. Study Identification

Unique Protocol Identification Number
NCT00302757
Brief Title
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

2. Study Status

Record Verification Date
May 2014
Overall Recruitment Status
Completed
Study Start Date
March 2006 (undefined)
Primary Completion Date
undefined (undefined)
Study Completion Date
July 2011 (Actual)

3. Sponsor/Collaborators

Name of the Sponsor
University Hospital Tuebingen

4. Oversight

5. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Non-Hodgkin Lymphoma
Keywords
NHL, low and high grade non-Hodgkin lymphoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
60 (Anticipated)

8. Arms, Groups, and Interventions

Intervention Type
Drug
Intervention Name(s)
Radioimmunotherapy
Intervention Type
Procedure
Intervention Name(s)
allogeneic hematopoietic cell transplantation
Primary Outcome Measure Information:
Title
treatment related toxicity
Title
engraftment
Secondary Outcome Measure Information:
Title
disease response
Title
relapse rate
Title
disease free survival
Title
overall survival
Title
graft versus host disease (GVHD)
Title
immunoreconstitution

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Wolfgang A Bethge, MD
Organizational Affiliation
Medical Center University of Tuebingen
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Donald Bunjes, MD
Organizational Affiliation
Medical Center University of Ulm
Official's Role
Principal Investigator
Facility Information:
Facility Name
Medical Center Charite Benjamin Franklin
City
Berlin
ZIP/Postal Code
12200
Country
Germany
Facility Name
University of Dresden Medical Center
City
Dresden
ZIP/Postal Code
D-01307
Country
Germany
Facility Name
Center for Marrow Transplantation, University of Essen
City
Essen
ZIP/Postal Code
45122
Country
Germany
Facility Name
Medical Center University of Goettingen
City
Goettingen
ZIP/Postal Code
37099
Country
Germany
Facility Name
Medical Center University of Hannover
City
Hannover
ZIP/Postal Code
30625
Country
Germany
Facility Name
Medical Center University of Leipzig
City
Leipzig
ZIP/Postal Code
04103
Country
Germany
Facility Name
Medical Center University of Muenster
City
Muenster
ZIP/Postal Code
48149
Country
Germany
Facility Name
South West German Cancer Center, University of Tuebingen Medical Center
City
Tuebingen
ZIP/Postal Code
72076
Country
Germany
Facility Name
Medical Center University of Ulm
City
Ulm
ZIP/Postal Code
89081
Country
Germany
Facility Name
Stiftung Deutsche Klinik für Diagnostik GmbH
City
Wiesbaden
ZIP/Postal Code
65191
Country
Germany
Facility Name
University of Wuerzburg Medical Center
City
Wuerzburg
ZIP/Postal Code
D-97070
Country
Germany

12. IPD Sharing Statement

Citations:
PubMed Identifier
22504934
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.
Results Reference
derived
PubMed Identifier
20530284
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.
Results Reference
derived
Links:
URL
http://www.onkologie-tuebingen.de
Description
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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

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