Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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UNKNOWN
PHASE3
360 participants
INTERVENTIONAL
2004-07-31
2014-12-31
Brief Summary
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Detailed Description
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The aim of this study is the comparison of the current standard (R-CHOP followed by myeloablative radio-chemotherapy and subsequent blood stem cell transplantation) to a new alternating induction regimen containing high dose Ara-C (R-CHOP/DHAP) followed by a high dose ARA-C containing myeloablative radio-chemotherapy and PBSCT.
This study will be performed as a prospective, randomized, open-label multicenter phase III trial. All patients will be initial randomized for standard treatment versus experimental treatment.
REFERENCE ARM:
The induction therapy consists of 6 cycles of a CHOP chemotherapy in combination with Rituximab. If the mantle cell lymphoma is progressive after 4 cycles of chemotherapy, patients will be taken off study. Patients achieving at least a partial remission after 6 cycles R-CHOP will proceed to intensified consolidation (Dexa-BEAM) with stem cell collection and subsequent myelo-ablative radio-chemotherapy (TBI/High Dose Cyclophosphamide) with autologous stem cells transplantation
EXPERIMENTAL ARM:
Initial cytoreductive chemotherapy comprises of alternating cycles of 3xCHOP and 3x DHAP plus Rituximab. Patients with progressive disease after 2 treatment cycles R-CHOP and 2x R-DHAP will be off study. Patients achieving at least a partial remission after 3x CHOP and 3x DHAP plus Rituximab will proceed to with stem cell collection. The subsequent myeloablative radio-chemotherapy with stem cell transplantation consists of a radiotherapy (TBI), high dose Ara-C and Melphalan.
The primary end point in this study is the time to treatment failure. The time to treatment failure will be defined as time from start of initial therapy until first failure. A failure will be defined as failure of initial therapy or progression of the lymphoma or death of the patient.
Using the data of the PBSCT group in the former European mantle cell study as baseline in a proportional hazard model, the improvement for the time to treatment failure expected by the new strategy can be expressed by reduction of relative risk (rr). A risk reduction to 52% which would correspond to a improvement of 20% in failure free survival after 3 years seems to be a clinical relevant improvement. For a working significance level alpha=0.05 and a power of 95% the number of events necessary for a one sided fixed sample trial is about 105. During this study the time to treatment failure will be monitored using an equivalent one-sided triangular sequential test.
In order to evaluate the impact of therapy on overall survival in this patients, a total follow up of about 12 years for this study is expected.
Conditions
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Keywords
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Study Design
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RANDOMIZED
PARALLEL
TREATMENT
NONE
Study Groups
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1
induction: R-CHOP consoldiation : TBI/Cyclo
Rituximab
antibody
Cyclophosphamide
chemotherapy
Doxorubicin
chemotherapy
Vincristine
chemotherapy
Prednisone
corticosteroide
BCNU
chemotherapy
Melphalan
chemotherapy
Etoposide
chemotherapy
G-CSF
growth factor
chemotherapy: R-CHOP
immuno-chemotherapy
chemotherapy: Dexa-BEAM
chemotherapy
stem cell harvest
procedure
total body irradiation
radiation
high-dose chemotherapy: Cyclophosphamide
chemotherapy
2
induction: R-CHOP/DHAP consolditaion: TBI/TAM
Rituximab
antibody
Cyclophosphamide
chemotherapy
Doxorubicin
chemotherapy
Vincristine
chemotherapy
Prednisone
corticosteroide
Cisplatinum
chemotherapy
Ara-C
chemotherapy
Dexamethasone
corticosteroide
Melphalan
chemotherapy
G-CSF
growth factor
chemotherapy: R-CHOP
immuno-chemotherapy
chemotherapy: R-DHAP
immuno-chemotherapy
stem cell harvest
procedure
total body irradiation
radiation
high-dose chemotherapy: Ara-C /Melphalan
chemotherapy
Interventions
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Rituximab
antibody
Cyclophosphamide
chemotherapy
Doxorubicin
chemotherapy
Vincristine
chemotherapy
Prednisone
corticosteroide
Cisplatinum
chemotherapy
Ara-C
chemotherapy
Dexamethasone
corticosteroide
BCNU
chemotherapy
Melphalan
chemotherapy
Etoposide
chemotherapy
G-CSF
growth factor
chemotherapy: R-CHOP
immuno-chemotherapy
chemotherapy: R-DHAP
immuno-chemotherapy
chemotherapy: Dexa-BEAM
chemotherapy
stem cell harvest
procedure
total body irradiation
radiation
high-dose chemotherapy: Cyclophosphamide
chemotherapy
high-dose chemotherapy: Ara-C /Melphalan
chemotherapy
Eligibility Criteria
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Inclusion Criteria
* Clinical stage II - IV (Ann Arbor)
* Previously untreated patients
* Age 18 - 65 years
* WHO performance \< 2
* Measurable disease (also: patients with isolated bone marrow involvement)
* Informed consent according to International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use/European Union Good Clinical Practice (ICH/EU GCP) and national/local regulations
Exclusion Criteria
* WHO performance status \> 2
* Known anti-murine antibody (HAMA) reactivity or known hypersensitivity to murine antibodies
* Previous lymphoma therapy with radiation, cytostatic drugs, anti-CD20 antibody or interferon
* Serious disease interfering with a regular therapy according to the study protocol:
* cardiac (e.g. manifest heart failure, coronary heart disease, uncontrolled hypertension)
* pulmonary (e.g. chronic lung disease with hypoxemia)
* endocrine (e.g. severe, not sufficiently controlled diabetes mellitus)
* renal insufficiency (unless caused by the lymphoma): creatinine \> 2x normal value and/or creatinine clearance \< 50 ml/min)
* impairment of liver function (unless caused by the lymphoma): transaminases \> 3x normal or bilirubin \> 2,0 mg/dl
* Patients with unresolved hepatitis B or C infection or known HIV infection
* Prior organ, bone marrow or peripheral blood stem cell transplantation
* Concomitant or previous malignancies within the last 5 years other than basal cell skin cancer or in situ uterine cervix cancer.
* Pregnancy or lactation
* Any psychological, familiar, sociological, or geographical condition potentially hampering compliance with the study protocol and follow up schedule
18 Years
65 Years
ALL
No
Sponsors
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German Low Grade Lymphoma Study Group
OTHER
Lymphoma Study Association
OTHER
European Mantle Cell Lymphoma Network
OTHER
Responsible Party
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University Hospital Grosshadern/European MCLNetwork
Principal Investigators
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Olivier Hermine, PhD
Role: PRINCIPAL_INVESTIGATOR
University Hospital Necker, Dept. of Adult Hematology
Wolfgang Hiddemann, PhD
Role: STUDY_CHAIR
University Hospital Großhadern/LMU, Dept. of Medicine III
Locations
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Groupe D´Etudes des Lymphomes De l´Adulte (GELA)
Paris, , France
German Low Grade Study Group (Glsg)
Munich, , Germany
The Maria Sklodowska Memorial, Cancer Center - Inst. of Oncology
Warsaw, , Poland
Countries
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Central Contacts
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Facility Contacts
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Guylène Chartier
Role: primary
Olivier Hermine, PhD
Role: backup
Michael Unterhalt, Dr.
Role: primary
Martin Dreyling, PhD
Role: backup
Jan Walewski, MD
Role: primary
Marek P Nowacki, MD
Role: backup
References
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Dreyling M, Lenz G, Hoster E, Van Hoof A, Gisselbrecht C, Schmits R, Metzner B, Truemper L, Reiser M, Steinhauer H, Boiron JM, Boogaerts MA, Aldaoud A, Silingardi V, Kluin-Nelemans HC, Hasford J, Parwaresch R, Unterhalt M, Hiddemann W. Early consolidation by myeloablative radiochemotherapy followed by autologous stem cell transplantation in first remission significantly prolongs progression-free survival in mantle-cell lymphoma: results of a prospective randomized trial of the European MCL Network. Blood. 2005 Apr 1;105(7):2677-84. doi: 10.1182/blood-2004-10-3883. Epub 2004 Dec 9.
Lenz G, Dreyling M, Hoster E, Wormann B, Duhrsen U, Metzner B, Eimermacher H, Neubauer A, Wandt H, Steinhauer H, Martin S, Heidemann E, Aldaoud A, Parwaresch R, Hasford J, Unterhalt M, Hiddemann W. Immunochemotherapy with rituximab and cyclophosphamide, doxorubicin, vincristine, and prednisone significantly improves response and time to treatment failure, but not long-term outcome in patients with previously untreated mantle cell lymphoma: results of a prospective randomized trial of the German Low Grade Lymphoma Study Group (GLSG). J Clin Oncol. 2005 Mar 20;23(9):1984-92. doi: 10.1200/JCO.2005.08.133. Epub 2005 Jan 24.
Hermine O, Jiang L, Walewski J, Bosly A, Thieblemont C, Szymczyk M, Pott C, Salles G, Feugier P, Hubel K, Haioun C, Casasnovas RO, Schmidt C, Bouabdallah K, Ribrag V, Kanz L, Durig J, Metzner B, Sibon D, Cheminant M, Burroni B, Klapper W, Hiddemann W, Unterhalt M, Hoster E, Dreyling M; European Mantle Cell Lymphoma Network. High-Dose Cytarabine and Autologous Stem-Cell Transplantation in Mantle Cell Lymphoma: Long-Term Follow-Up of the Randomized Mantle Cell Lymphoma Younger Trial of the European Mantle Cell Lymphoma Network. J Clin Oncol. 2023 Jan 20;41(3):479-484. doi: 10.1200/JCO.22.01780. Epub 2022 Dec 5.
Hermine O, Hoster E, Walewski J, Bosly A, Stilgenbauer S, Thieblemont C, Szymczyk M, Bouabdallah R, Kneba M, Hallek M, Salles G, Feugier P, Ribrag V, Birkmann J, Forstpointner R, Haioun C, Hanel M, Casasnovas RO, Finke J, Peter N, Bouabdallah K, Sebban C, Fischer T, Duhrsen U, Metzner B, Maschmeyer G, Kanz L, Schmidt C, Delarue R, Brousse N, Klapper W, Macintyre E, Delfau-Larue MH, Pott C, Hiddemann W, Unterhalt M, Dreyling M; European Mantle Cell Lymphoma Network. Addition of high-dose cytarabine to immunochemotherapy before autologous stem-cell transplantation in patients aged 65 years or younger with mantle cell lymphoma (MCL Younger): a randomised, open-label, phase 3 trial of the European Mantle Cell Lymphoma Network. Lancet. 2016 Aug 6;388(10044):565-75. doi: 10.1016/S0140-6736(16)00739-X. Epub 2016 Jun 14.
Delfau-Larue MH, Klapper W, Berger F, Jardin F, Briere J, Salles G, Casasnovas O, Feugier P, Haioun C, Ribrag V, Thieblemont C, Unterhalt M, Dreyling M, Macintyre E, Pott C, Hermine O, Hoster E; European Mantle Cell Lymphoma Network. High-dose cytarabine does not overcome the adverse prognostic value of CDKN2A and TP53 deletions in mantle cell lymphoma. Blood. 2015 Jul 30;126(5):604-11. doi: 10.1182/blood-2015-02-628792. Epub 2015 May 28.
Hoster E, Klapper W, Hermine O, Kluin-Nelemans HC, Walewski J, van Hoof A, Trneny M, Geisler CH, Di Raimondo F, Szymczyk M, Stilgenbauer S, Thieblemont C, Hallek M, Forstpointner R, Pott C, Ribrag V, Doorduijn J, Hiddemann W, Dreyling MH, Unterhalt M. Confirmation of the mantle-cell lymphoma International Prognostic Index in randomized trials of the European Mantle-Cell Lymphoma Network. J Clin Oncol. 2014 May 1;32(13):1338-46. doi: 10.1200/JCO.2013.52.2466. Epub 2014 Mar 31.
Pott C, Hoster E, Delfau-Larue MH, Beldjord K, Bottcher S, Asnafi V, Plonquet A, Siebert R, Callet-Bauchu E, Andersen N, van Dongen JJ, Klapper W, Berger F, Ribrag V, van Hoof AL, Trneny M, Walewski J, Dreger P, Unterhalt M, Hiddemann W, Kneba M, Kluin-Nelemans HC, Hermine O, Macintyre E, Dreyling M. Molecular remission is an independent predictor of clinical outcome in patients with mantle cell lymphoma after combined immunochemotherapy: a European MCL intergroup study. Blood. 2010 Apr 22;115(16):3215-23. doi: 10.1182/blood-2009-06-230250. Epub 2009 Dec 23.
Other Identifiers
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MCL2004-2
Identifier Type: -
Identifier Source: org_study_id