Freiburg ZNS-NHL Study

Freiburg ZNS-NHL Study: Therapy for Patients With Primary Non-Hodgkin Lymphoma of the CNS - Sequential High Dosage Chemotherapy With Autologous Peripheral Blood Stem Cell Plantation

The purpose of this study is to determine whether combined chemotherapy [rituximab plus high dosage methotrexate (max. 2 cycles) followed by arabinoside/thiotepa (max. 2 cycles) followed by high dosage carmustin/thiotepa] followed by peripheral blood stem cell transplantation is effective in the treatment of cerebral Non Hodgkin lymphoma [PCNSL].

Study Overview

• Status: Unknown
• Conditions: Primary Non Hodgkin Lymphoma of the Central Nervous System
• Intervention / Treatment: Drug: methotrexate; Drug: Rituximab; Drug: Cytarabine; Drug: Thiotepa; Drug: Carmustin

• Study Type: Interventional
• Enrollment (Anticipated): 78
• Phase: Phase 2

Contacts and Locations

Study Locations

• Germany
  • Freiburg, Germany, 79106
    • Recruiting
    • University Hospital Freiburg
    • Contact: Gerald Illerhaus, Dr.; Phone Number: 00497612703785; Email: Gerald.Illerhaus@uniklinik-freiburg.de
    • Contact: Andreas Zähringer; Phone Number: 00497612707378; Email: andreas.zaehringer@uniklinik-freiburg.de

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• group A: first diagnosis of PCNSL, histologically confirmed
• group B: relapse or progression of PCNSL after MTX containing chemotherapy
• age 18 - 65 years
• not legally incompetent, physically or mentally incapable of giving consent
• written signed and dated informed consent of the legal representative and - if possible - of the patient

Exclusion Criteria:

• manifestations of further lymphoma outside the CNS
• sero-positive for HIV
• severe pulmonary, cardiac, hepatic, renal impairment
• neutrophil count < 2.000/µl, platelet count < 100.000/µl
• pulmonary disease with IVC < 55%, DLCO < 40%
• cardiac ejection fraction < 50%, uncontrolled malign arrhythmia
• creatinine > 1,5 mg% or creatinine-clearance < 50ml/min
• bilirubin > 2mg/dl
• ascites or pleural effusion (> 500ml)
• pregnancy o r lactation
• women with childbearing potential without sufficient contraception
• participation in another clinical trial within the last 30 days prior to the begin or parallel to this study
• known or current drug or alcohol abuse
• known hypersensitivity against methotrexate, cytarabine, thiotepa, BCNU rituximab, leukovorin, dexamethasone, neupogen and neulasta.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: A; first diagnosis of PCNSL: combined chemotherapy with methotrexate	Drug: methotrexate; 8000mg/m2 i.v., max. 2 cycles; Other Names: MTX; Drug: Rituximab; 375mg/m2, max. 8 times; Drug: Cytarabine; 3000mg/m2 die i.v., 2 days (max. 2 cycles); Other Names: Arabinoside; Drug: Thiotepa; 40mg/m2 i.v. (max. 2 cycles) 2 x 5mg/kg/die i.v. for 2 days; Drug: Carmustin; 400mg/m2 i.v. for 1 day; Other Names: BCNU; Bis-Chlorethyl-Nitrosourea
Experimental: B; Patients with relapse or progressive disease of PCNSL after methotrexate containing chemotherapy	Drug: Rituximab; 375mg/m2, max. 8 times; Drug: Cytarabine; 3000mg/m2 die i.v., 2 days (max. 2 cycles); Other Names: Arabinoside; Drug: Thiotepa; 40mg/m2 i.v. (max. 2 cycles) 2 x 5mg/kg/die i.v. for 2 days; Drug: Carmustin; 400mg/m2 i.v. for 1 day; Other Names: BCNU; Bis-Chlorethyl-Nitrosourea

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Complete response rate	30 days after blood stem cell transplantation

Secondary Outcome Measures

Outcome Measure	Time Frame
Duration of response	within 5 years
Overall survival time	within 5 years
(Serious) adverse events ([S]AEs)	within 30 days after treatment
Neuropsychological state according to Mini-Mental State	within 5 years
Neuropsychological assessment (digit span, Hopkins verbal Learning Test-Revised, Trials 1-3, Brief Test of Attention, Trial Making Test, Grooved Pegboard, 6. HVLT-R , EORTC L C30 , EORTC BN20)	within 5 years

Collaborators and Investigators

• Sponsor: University Hospital Freiburg
• Collaborators: University Hospital Tuebingen
• Investigators: Principal Investigator: Jürgen Finke, Prof. Dr., University Medical Center Freiburg, Dept. of Internal Medicine I - Hematology and Oncology

Publications and helpful links

General Publications

• Illerhaus G, Marks R, Ihorst G, Guttenberger R, Ostertag C, Derigs G, Frickhofen N, Feuerhake F, Volk B, Finke J. High-dose chemotherapy with autologous stem-cell transplantation and hyperfractionated radiotherapy as first-line treatment of primary CNS lymphoma. J Clin Oncol. 2006 Aug 20;24(24):3865-70. doi: 10.1200/JCO.2006.06.2117. Epub 2006 Jul 24.
• Kasenda B, Ihorst G, Schroers R, Korfel A, Schmidt-Wolf I, Egerer G, von Baumgarten L, Roth A, Bloehdorn J, Mohle R, Binder M, Keller U, Lamprecht M, Pfreundschuh M, Valk E, Fricker H, Schorb E, Fritsch K, Finke J, Illerhaus G. High-dose chemotherapy with autologous haematopoietic stem cell support for relapsed or refractory primary CNS lymphoma: a prospective multicentre trial by the German Cooperative PCNSL study group. Leukemia. 2017 Dec;31(12):2623-2629. doi: 10.1038/leu.2017.170. Epub 2017 May 31.
• Illerhaus G, Kasenda B, Ihorst G, Egerer G, Lamprecht M, Keller U, Wolf HH, Hirt C, Stilgenbauer S, Binder M, Hau P, Edinger M, Frickhofen N, Bentz M, Mohle R, Roth A, Pfreundschuh M, von Baumgarten L, Deckert M, Hader C, Fricker H, Valk E, Schorb E, Fritsch K, Finke J. High-dose chemotherapy with autologous haemopoietic stem cell transplantation for newly diagnosed primary CNS lymphoma: a prospective, single-arm, phase 2 trial. Lancet Haematol. 2016 Aug;3(8):e388-97. doi: 10.1016/S2352-3026(16)30050-3. Epub 2016 Jul 13.

Study record dates

Study Major Dates

• Study Start: January 1, 2007
• Primary Completion (Anticipated): May 1, 2013
• Study Completion (Anticipated): August 1, 2013

Study Registration Dates

• First Submitted: March 26, 2008
• First Submitted That Met QC Criteria: March 28, 2008
• First Posted (Estimate): March 31, 2008

Study Record Updates

• Last Update Posted (Estimate): November 17, 2009
• Last Update Submitted That Met QC Criteria: November 16, 2009
• Last Verified: November 1, 2009

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma; Lymphoma, Non-Hodgkin; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Antirheumatic Agents; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Antineoplastic Agents, Immunological; Dermatologic Agents; Reproductive Control Agents; Abortifacient Agents, Nonsteroidal; Abortifacient Agents; Folic Acid Antagonists; Rituximab; Cytarabine; Methotrexate; Thiotepa
• Other Study ID Numbers: ZNS-00465