Allo-hNHL (FluBuCy)

Open, Multicentral, Randomised Phase II Study of Allogene Stem Cell Transplantation After Pretreatment With Fludarabin, Busulfan, Cyclophospahmid and GVHD-prophylaxis With or Without Rituximab in Patients With Recidivation of High Grade Non-hodgkin's Lymphoma in Special Risk Situation in the Age of 18 - 65

DSHNHL R3 is a randomized clinical phase II study. The main objective is to estimate the efficacy of rituximab as a prophylactic medication for prevention of graft-versus-host-disease after allogeneic peripheral stem cell transplantation in patients with a high risk relapse of aggressive B-cell Non-Hodgkin's lymphoma. The most important secondary objective is to estimate the efficacy of allogeneic stem cell transplantation in this clinical situation.

Study Overview

• Status: Completed
• Conditions: Non-Hodgkin's Lymphoma
• Intervention / Treatment: Drug: standard GVHD prophylaxis; Drug: rituximab

Detailed Description

Patients in the age of 18 to 65 years with a high- risk relapse of a histology proven aggressive Non-Hodgkin's-lymphoma are eligible for the trial. Aggressive Non-Hodgkin's lymphoma within this study is defined as:

B-NHL:

follicular lymphoma grade III° lymphoblastic (precursor) lymphoma diffuse large cell cell lymphoma any subtype and variant including primary mediastinal lymphoma mantle cell lymphoma, blastic variant

T-NHL:

precursor T cell lymphoma peripheral T cell lymphoma, any subtype and variant angioimmunoblastic lymphoma anaplastic large cell lymphoma, any subtype NK / T cell lymphoma High risk relapsed or progressive disease is defined as (a) primary progressive disease, (b) early relapse after less than 12 month of remission duration and at least one risk factor according to the international prognostic index (IPI), (c) relapse or progression after high dose chemotherapy and autologous transplantation, (d) relapse or progression and lack of an autologous stem cell product.

Patients with this type of progression / relapse should receive rituximab plus ifosfamide/carboplatin/etoposide (R-ICE) or rituximab plus dexamethasone/high dose ARA-C/cisplatinum as salvage therapy (recommendation, not part of study medication). In patients biwth T cell lymphoma rituximab may be replaced by alemtuzumab. If at least stable disease is achieved, patients can be definitely included.

With inclusion, patients were randomized to receive either 375 mg/ m2 of rituximab at weeks 3, 4, 5, 6, 25, 26, 27, 28 after allogeneic stem cell transplantation or no additional medication.

Conditioning for transplantation consisted of Fludarabine 125 mg/m2, Busulfan 12 mg/kg and cyclophosphamide 120 mg/kg.

Short-term (day 1 to day 28) mycophenolat mofetil and tacrolimus are used as basis GVHD prophylaxis in all patients. Anti-thymocyte globulin can be used due to the centres decision in patients with unrelated donors

• Study Type: Interventional
• Enrollment (Actual): 84
• Phase: Phase 2

Contacts and Locations

Study Locations

• Germany
  • Göttingen, Germany, D.37075
    • University Hospital Goettingen
  • Hamburg, Germany, D-20099
    • Asklepios Klinik St. Georg
  • Münster, Germany
    • KMT-Zentrum Medizinische Klinik A
  • Baden-Würtenberg
    • Heidelberg, Baden-Würtenberg, Germany
      • Universitatsklinikum Heidelberg
  • Hessen
    • Marburg, Hessen, Germany
      • Universitätsklinikum Marburg
  • Saarland
    • Homburg, Saarland, Germany
      • Universitätsklinikum und Poliklinik

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:

• histology proven aggressive non Hodgkin's lymphoma and
• primary progressive disease or
• early relapse after less than 12 month of remission duration and at least one risk factor according to the international prognostic index (IPI or
• relapse or progression after high dose chemotherapy and autologous transplantation or
• relapse or progression and lack of an autologous stem cell product.

Exclusion Criteria:

• severe comorbidity or impaired organ function
• hypersensitivity to used drugs
• HIV positivity
• active hepatitis
• other active malignant disease

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
OTHER: A; Patients receiving no rituximab as GVHD prophylaxis after allogeneic SZT and only standard GVHD prophylaxis (tacrolimus with aimed serum level of 10 ng / ml and mycophenolat mofetil 2 x 1 g p.o. day 1 to 28 after allogeneic SZT	Drug: standard GVHD prophylaxis; Application of tacrolimus from day -1 with a goal of tacrolimus serum concentration of 10 ng / ml Aplication of mycophenolat mofetil from day +1 to day +28 in a dose of 2 x 1g per day
EXPERIMENTAL: B; rituximab in addition to standard GVHD prophylaxis	Drug: rituximab; Patients receiving 375 mg/ m2 of rituximab at weeks 3, 4, 5, 6, 25, 26, 27, 28 after allogeneic stem cell transplantation in addition to standard GVHD prophylaxis (tacrolimus with aimed serum level of 10 ng / ml and mycophenolat mofetil 2 x 1 g p.o. day 1 to 28 after allogeneic SZT

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The specific measure that will be used to determine the effect of the intervention(s) or, for observational studies, related to core objectives of the study and receiving the most emphasis in assessment. (a) rate of acute GVHD grade II-IV after one year	One year after allogeneic stem cell transplantation

Secondary Outcome Measures

Outcome Measure	Time Frame
progression free survival, progression rate, non-relapse mortality, rate of grade 3-4 infectious adverse event, chronic GVHD	one and three years after allogeneic SZT

Collaborators and Investigators

• Sponsor: Institut fuer anwendungsorientierte Forschung und klinische Studien GmbH
• Collaborators: German High-Grade Non-Hodgkin's Lymphoma Study Group; University Hospital Goettingen
• Investigators: Study Director: Bertram Glass, Prof. MD., Asklepios Klinik St. Georg

Publications and helpful links

General Publications

• Glass B, Hasenkamp J, Wulf G, Dreger P, Pfreundschuh M, Gramatzki M, Silling G, Wilhelm C, Zeis M, Gorlitz A, Pfeiffer S, Hilgers R, Truemper L, Schmitz N; German High-Grade Lymphoma Study Group. Rituximab after lymphoma-directed conditioning and allogeneic stem-cell transplantation for relapsed and refractory aggressive non-Hodgkin lymphoma (DSHNHL R3): an open-label, randomised, phase 2 trial. Lancet Oncol. 2014 Jun;15(7):757-66. doi: 10.1016/S1470-2045(14)70161-5. Epub 2014 May 11.

Study record dates

Study Major Dates

• Study Start: April 1, 2004
• Primary Completion (ACTUAL): March 1, 2009
• Study Completion (ACTUAL): April 1, 2011

Study Registration Dates

• First Submitted: September 13, 2005
• First Submitted That Met QC Criteria: November 4, 2008
• First Posted (ESTIMATE): November 5, 2008

Study Record Updates

• Last Update Posted (ACTUAL): January 13, 2020
• Last Update Submitted That Met QC Criteria: January 9, 2020
• Last Verified: January 1, 2020

More Information

Terms related to this study

• Keywords: Non-Hodgkin's lymphoma; rituximab; graft-versus-host disease; diffuse large B cell lymphoma; peripheral t cell lymphoma; graft-versus-lymphoma effect; allogeneic haematopoietic stem cell transplantation; relapsed or primary progressive aggressive Non-Hodgkin's lymphoma
• 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; Antirheumatic Agents; Antineoplastic Agents; Immunologic Factors; Antineoplastic Agents, Immunological; Rituximab
• Other Study ID Numbers: DSHNHL 2004-R3