A Study of Zevalin and Simultaneous Application of BEAM High-dose Chemotherapy Followed by Autologous Stem Cell Transplantation in Refractory and Relapsed Aggressive Non-Hodgkin Lymphomas (escZ-BEAM)
Primary Purpose
Primary Non-Hodgkin-Lymphoma, Refractory Non-Hodgkin-Lymphoma, CD20+ Aggressive Non-Hodgkin's Lymphoma
Status
Completed
Phase
Phase 2
Locations
Germany
Study Type
Interventional
Intervention
Zevalin
Sponsored by
About this trial
This is an interventional treatment trial for Primary Non-Hodgkin-Lymphoma focused on measuring High-Dose Radio-Immuno- and Chemotherapy, stem cell transplantation, 90Y-Ibritumomab-Tiuxetan
Eligibility Criteria
Inclusion Criteria:
- Age: 18 - 65 years
- Risk group: 1) Progression on primary therapy 2) Initial or subsequent relapse
- Histology: Diagnosis of relapsed aggressive non-Hodgkin lymphoma, whenever possible confirmed by an excision biopsy of a lymph node or by a sufficiently large biopsy of an extranodal site if no lymph node lesion is present. The expression of the CD20 antigen must be demonstrated in the primary lesion or in the relapse. Specifically, the following entities can be treated in this study:
B-NHL:
Grade III B follicular lymphoma Diffuse B-cell lymphoma centroblastic immunoblastic plasmoblastic anaplastic-large-cell T-cell rich B-cell lymphoma Primary effusion lymphoma Intravascular B-cell lymphoma Primary mediastinal B-cell lymphoma Mantle cell lymphoma, blastoid Variants of Burkitt's lymphoma Aggressive marginal zone lymphoma (monocytoid)
- General condition: General condition ECOG 0-3 (Karnofsky: 40 - 100 %); for definition see Annex 14.10
- Presence of declaration of participation of the center and the patient's written consent form
Exclusion Criteria:
- Prior mediastinal or extensive abdominal irradiation
- Prior high-dose therapy and autologous stem cell transplantation
- Impairment of renal function (creatinine > 2.5 mg/dL, creatinine clearance < 20 mL/min)
- Impairment of hepatic function (bilirubin > 2.0 mg/dL, cholinesterase [CHE] < 2000 U/L)
- Impairment of pulmonary function (transfer lung factor for CO [TLCO] < 50 %, forced expiratory volume in 1 sec [FEV1] < 60 %, vital capacity [VC] < 60 %)
- Relevant deterioration of the above organ functions on salvage therapy
- Failure of stem cell mobilization
- Active viral hepatitis
- HIV infection
- Other active or not conclusively curatively treated malignoma
- Severe concomitant psychiatric illness or suspected lack of patient compliance
- Pregnancy or unreliable contraception
- Highly dynamic progress of lymphoma (lactate dehydrogenase [LDH] > 1.5 x upper limit of normal [ULN]) after salvage therapy immediately prior to radioimmunotherapy
Sites / Locations
- Institut für anwendungsorientierte Forschung und klinische Studien (IFS GmbH)
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
1
Arm Description
Outcomes
Primary Outcome Measures
The primary outcome variable is the highest achievable dose level of 90Y-Zevalin administered immediately before BEAM high-dose therapy and followed by autologous stem cell transplantation.
Secondary Outcome Measures
Treatment related mortality (TRM), freedom from progression (FFP), Survival (OS), progression free survival (PFS) grade III -IV toxicity (CTC) on lung, liver and kidney
Full Information
NCT ID
NCT00521560
First Posted
August 27, 2007
Last Updated
February 13, 2013
Sponsor
Institut fuer anwendungsorientierte Forschung und klinische Studien GmbH
1. Study Identification
Unique Protocol Identification Number
NCT00521560
Brief Title
A Study of Zevalin and Simultaneous Application of BEAM High-dose Chemotherapy Followed by Autologous Stem Cell Transplantation in Refractory and Relapsed Aggressive Non-Hodgkin Lymphomas
Acronym
escZ-BEAM
Official Title
Phase I/II Study Concomitant High-Dose Radio-Immuno- and Chemotherapy With Simultaneous Application of Zevalin and BEAM Followed by Autologous Peripheral Stem Cell Transplantation in Relapsed and Refractory CD 20+ Non-Hodgkin's Lymphoma
Study Type
Interventional
2. Study Status
Record Verification Date
February 2013
Overall Recruitment Status
Completed
Study Start Date
March 2006 (undefined)
Primary Completion Date
August 2009 (Actual)
Study Completion Date
August 2012 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Institut fuer anwendungsorientierte Forschung und klinische Studien GmbH
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
Phase II Study Concomitant High-Dose Radio-Immuno- and Chemotherapy with simultaneous application of Zevalin and BEAM followed by autologous peripheral stem cell transplantation in relapsed and refractory CD 20+ Non-Hodgkin's lymphoma
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Primary Non-Hodgkin-Lymphoma, Refractory Non-Hodgkin-Lymphoma, CD20+ Aggressive Non-Hodgkin's Lymphoma
Keywords
High-Dose Radio-Immuno- and Chemotherapy, stem cell transplantation, 90Y-Ibritumomab-Tiuxetan
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
28 (Actual)
8. Arms, Groups, and Interventions
Arm Title
1
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
Zevalin
Other Intervention Name(s)
90Y-Ibritumomab-Tiuxetan
Intervention Description
All applications of 90Y-Ibritumomab-Tiuxetan will be preceded by rituximab infusions at a dose of 250 mg/m2 at days -21 and day -14 (DL1) or day -12 (DL2) or day -10 (DL3-5), respectively.
High dose therapy will be given as BEAM
Primary Outcome Measure Information:
Title
The primary outcome variable is the highest achievable dose level of 90Y-Zevalin administered immediately before BEAM high-dose therapy and followed by autologous stem cell transplantation.
Time Frame
3 Year
Secondary Outcome Measure Information:
Title
Treatment related mortality (TRM), freedom from progression (FFP), Survival (OS), progression free survival (PFS) grade III -IV toxicity (CTC) on lung, liver and kidney
Time Frame
3 Years
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:
Age: 18 - 65 years
Risk group: 1) Progression on primary therapy 2) Initial or subsequent relapse
Histology: Diagnosis of relapsed aggressive non-Hodgkin lymphoma, whenever possible confirmed by an excision biopsy of a lymph node or by a sufficiently large biopsy of an extranodal site if no lymph node lesion is present. The expression of the CD20 antigen must be demonstrated in the primary lesion or in the relapse. Specifically, the following entities can be treated in this study:
B-NHL:
Grade III B follicular lymphoma Diffuse B-cell lymphoma centroblastic immunoblastic plasmoblastic anaplastic-large-cell T-cell rich B-cell lymphoma Primary effusion lymphoma Intravascular B-cell lymphoma Primary mediastinal B-cell lymphoma Mantle cell lymphoma, blastoid Variants of Burkitt's lymphoma Aggressive marginal zone lymphoma (monocytoid)
General condition: General condition ECOG 0-3 (Karnofsky: 40 - 100 %); for definition see Annex 14.10
Presence of declaration of participation of the center and the patient's written consent form
Exclusion Criteria:
Prior mediastinal or extensive abdominal irradiation
Prior high-dose therapy and autologous stem cell transplantation
Impairment of renal function (creatinine > 2.5 mg/dL, creatinine clearance < 20 mL/min)
Impairment of hepatic function (bilirubin > 2.0 mg/dL, cholinesterase [CHE] < 2000 U/L)
Impairment of pulmonary function (transfer lung factor for CO [TLCO] < 50 %, forced expiratory volume in 1 sec [FEV1] < 60 %, vital capacity [VC] < 60 %)
Relevant deterioration of the above organ functions on salvage therapy
Failure of stem cell mobilization
Active viral hepatitis
HIV infection
Other active or not conclusively curatively treated malignoma
Severe concomitant psychiatric illness or suspected lack of patient compliance
Pregnancy or unreliable contraception
Highly dynamic progress of lymphoma (lactate dehydrogenase [LDH] > 1.5 x upper limit of normal [ULN]) after salvage therapy immediately prior to radioimmunotherapy
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Bertram Glass, Prof. Dr.
Organizational Affiliation
German Society of Cancer e.V.
Official's Role
Study Director
First Name & Middle Initial & Last Name & Degree
Martin Gramatzki, MD PhD
Organizational Affiliation
Städtisches Krankenhaus Kiel, II. Med. Uniklinik, Kiel, Germany
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Mattias Witzens Harig, MD PhD
Organizational Affiliation
Abteilung Innere Medizin V, Hämatologie, Onkologie, Heidelberg, Germany
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Bernd Hertenstein, MD PhD
Organizational Affiliation
Klinikum Bremen-Mitte gGmbH, Medizinische Klinik I, Bremen, Germany
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Georg Heß, MD PhD
Organizational Affiliation
III Med., Schwerpunkt Hämatologie / Onkologie, Mainz, Germany
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Dorothea Kofahl-Krause, MD PhD
Organizational Affiliation
MHH, Hämatologie, Hämostaseologie und Onkologie, Hannover, Germany
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Norbert Schmitz, MD PhD
Organizational Affiliation
Asklepios Klinik St. Georg, Hämatologische Abt., Hamburg, Germany
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Jörg Schubert, MD PhD
Organizational Affiliation
Universitätskliniken d. Saarlandes, Med. I, Homburg/Saar, Germany
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Lutz Uharek Uharek, MD PhD
Organizational Affiliation
Charité - Campus Benjamin Franklin, Med. III, Berlin, Germany
Official's Role
Principal Investigator
Facility Information:
Facility Name
Institut für anwendungsorientierte Forschung und klinische Studien (IFS GmbH)
City
Göttingen
ZIP/Postal Code
37075
Country
Germany
12. IPD Sharing Statement
Learn more about this trial
A Study of Zevalin and Simultaneous Application of BEAM High-dose Chemotherapy Followed by Autologous Stem Cell Transplantation in Refractory and Relapsed Aggressive Non-Hodgkin Lymphomas
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