escZ-BEAM: 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

Sponsor

Institut fuer anwendungsorientierte Forschung und klinische Studien GmbH (Other)

Overall Status

Completed

CT.gov ID

NCT00521560

Collaborator

(none)

Enrollment

Location

Arm

Duration (Months)

0.4

Patients Per Site Per Month

Study Details

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

Condition or Disease	Intervention/Treatment	Phase
Primary Non-Hodgkin-Lymphoma Refractory Non-Hodgkin-Lymphoma CD20+ Aggressive Non-Hodgkin's Lymphoma	Drug: Zevalin	Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

28 participants

Allocation:

Non-Randomized

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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 Start Date :

Mar 1, 2006

Actual Primary Completion Date :

Aug 1, 2009

Actual Study Completion Date :

Aug 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 1	Drug: Zevalin 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 Other Names: 90Y-Ibritumomab-Tiuxetan

Arm

Intervention/Treatment

Experimental: 1

Drug: Zevalin

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

Other Names:

90Y-Ibritumomab-Tiuxetan

Outcome Measures

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. [3 Year]

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 [3 Years]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Institut für anwendungsorientierte Forschung und klinische Studien (IFS GmbH)	Göttingen		Germany	37075

Sponsors and Collaborators

Institut fuer anwendungsorientierte Forschung und klinische Studien GmbH

Investigators

Study Director: Bertram Glass, Prof. Dr., German Society of Cancer e.V.
Principal Investigator: Martin Gramatzki, MD PhD, Städtisches Krankenhaus Kiel, II. Med. Uniklinik, Kiel, Germany
Principal Investigator: Mattias Witzens Harig, MD PhD, Abteilung Innere Medizin V, Hämatologie, Onkologie, Heidelberg, Germany
Principal Investigator: Bernd Hertenstein, MD PhD, Klinikum Bremen-Mitte gGmbH, Medizinische Klinik I, Bremen, Germany
Principal Investigator: Georg Heß, MD PhD, III Med., Schwerpunkt Hämatologie / Onkologie, Mainz, Germany
Principal Investigator: Dorothea Kofahl-Krause, MD PhD, MHH, Hämatologie, Hämostaseologie und Onkologie, Hannover, Germany
Principal Investigator: Norbert Schmitz, MD PhD, Asklepios Klinik St. Georg, Hämatologische Abt., Hamburg, Germany
Principal Investigator: Jörg Schubert, MD PhD, Universitätskliniken d. Saarlandes, Med. I, Homburg/Saar, Germany
Principal Investigator: Lutz Uharek Uharek, MD PhD, Charité - Campus Benjamin Franklin, Med. III, Berlin, Germany