Clinical trial NCT00521560: 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
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
Overall status: COMPLETED
Phase: PHASE2
Conditions: 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
Lead sponsor: Institut fuer anwendungsorientierte Forschung und klinische Studien GmbH
Sponsor class: OTHER
First posted: 2007-08-28
Enrollment: 28
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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


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

Primary outcomes:
measure: 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.
timeFrame: 3 Year
Secondary outcomes:
measure: Treatment related mortality (TRM), freedom from progression (FFP), Survival (OS), progression free survival (PFS) grade III -IV toxicity (CTC) on lung, liver and kidney
timeFrame: 3 Years
Other outcomes:
Locations:
city: Göttingen
country: Germany
facility: Institut für anwendungsorientierte Forschung und klinische Studien (IFS GmbH)
Study officials:
affiliation: German Society of Cancer e.V.
name: Bertram Glass, Prof. Dr.
role: STUDY_DIRECTOR
affiliation: Städtisches Krankenhaus Kiel, II. Med. Uniklinik, Kiel, Germany
name: Martin Gramatzki, MD PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Abteilung Innere Medizin V, Hämatologie, Onkologie, Heidelberg, Germany
name: Mattias Witzens Harig, MD PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Klinikum Bremen-Mitte gGmbH, Medizinische Klinik I, Bremen, Germany
name: Bernd Hertenstein, MD PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: III Med., Schwerpunkt Hämatologie / Onkologie, Mainz, Germany
name: Georg Heß, MD PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: MHH, Hämatologie, Hämostaseologie und Onkologie, Hannover, Germany
name: Dorothea Kofahl-Krause, MD PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Asklepios Klinik St. Georg, Hämatologische Abt., Hamburg, Germany
name: Norbert Schmitz, MD PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Universitätskliniken d. Saarlandes, Med. I, Homburg/Saar, Germany
name: Jörg Schubert, MD PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Charité - Campus Benjamin Franklin, Med. III, Berlin, Germany
name: Lutz Uharek Uharek, MD PhD
role: PRINCIPAL_INVESTIGATOR
References: