ClinicalTrials.gov
ClinicalTrials.gov Menu

Efficacy of R-CHOP vs R-CHOP/R-DHAP in Untreated MCL

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT00209222
Recruitment Status : Unknown
Verified July 2009 by European Mantle Cell Lymphoma Network.
Recruitment status was:  Recruiting
First Posted : September 21, 2005
Last Update Posted : September 10, 2012
Sponsor:
Collaborators:
German Low Grade Lymphoma Study Group
Lymphoma Study Association
Information provided by:
European Mantle Cell Lymphoma Network

Brief Summary:
The aim of this study is to determine whether alternating courses of cyclophosphamide, doxorubicin, vincristine, prednisone/dexamethasone, cytarabine, cisplatin (CHOP/DHAP) plus rituximab followed by total body irradiation [TBI]/high dose cytarabine [ARA-C]/melphalan-peripheral blood stem cell transplantation (TAM-PBSCT) can improve the time to treatment failure compared to CHOP plus rituximab followed by standard PBSCT (dexamethasone, carmustine, cytarabine, etoposide, and melphalan [Dexa-BEAM]/TBI/high dose cyclophosphamide) in patients with untreated mantle cell lymphoma.

Condition or disease Intervention/treatment Phase
Lymphoma, Mantle-Cell Drug: Rituximab Drug: Cyclophosphamide Drug: Doxorubicin Drug: Vincristine Drug: Prednisone Drug: Cisplatinum Drug: Ara-C Drug: Dexamethasone Drug: BCNU Drug: Melphalan Drug: Etoposide Drug: G-CSF Procedure: chemotherapy: R-CHOP Procedure: chemotherapy: R-DHAP Procedure: chemotherapy: Dexa-BEAM Procedure: stem cell harvest Procedure: total body irradiation Procedure: high-dose chemotherapy: Cyclophosphamide Procedure: high-dose chemotherapy: Ara-C /Melphalan Phase 3

  Hide Detailed Description

Detailed Description:

Recently, a prospective randomized intergroup trial of the European MCL Network has shown that a myeloablative radio-chemotherapy followed by autologous stem cell transplantation (PBSCT) improves event-free survival (EFS) when compared to a interferon alpha maintenance therapy after a CHOP-like induction. However, the CR rate after the CHOP induction was still low (<20%). Thus, several studies have been conducted to increase the CR rate of induction therapy to further improve event-free and overall survival. Two recent phase II trials suggest that induction regimens containing high dose Ara-C may significantly improve the CR rate up to 80%. In addition, a number of studies provide evidence that the humanized anti-CD20 antibody Rituximab may induce significant responses in relapsed MCL. A prospective randomized study of the GLSG demonstrated that a combined immuno-chemotherapy (CHOP plus Rituximab) induces a significantly higher response rate than CHOP alone.

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.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 360 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Efficacy of 6x R-CHOP Followed by Myeloablative Radiochemotherapy and Autologous Stem Cell Transplantation vs. 3 x (R-CHOP/R-DHAP) Followed by a High Dose ARA-C Containing Myeloablative Regimen and Autologous Stem Cell Transplantation
Study Start Date : July 2004
Estimated Primary Completion Date : December 2014
Estimated Study Completion Date : December 2014

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lymphoma

Arm Intervention/treatment
Active Comparator: 1
induction: R-CHOP consoldiation : TBI/Cyclo
Drug: Rituximab
antibody

Drug: Cyclophosphamide
chemotherapy

Drug: Doxorubicin
chemotherapy

Drug: Vincristine
chemotherapy

Drug: Prednisone
corticosteroide

Drug: BCNU
chemotherapy

Drug: Melphalan
chemotherapy

Drug: Etoposide
chemotherapy

Drug: G-CSF
growth factor

Procedure: chemotherapy: R-CHOP
immuno-chemotherapy

Procedure: chemotherapy: Dexa-BEAM
chemotherapy

Procedure: stem cell harvest
procedure

Procedure: total body irradiation
radiation

Procedure: high-dose chemotherapy: Cyclophosphamide
chemotherapy

Experimental: 2
induction: R-CHOP/DHAP consolditaion: TBI/TAM
Drug: Rituximab
antibody

Drug: Cyclophosphamide
chemotherapy

Drug: Doxorubicin
chemotherapy

Drug: Vincristine
chemotherapy

Drug: Prednisone
corticosteroide

Drug: Cisplatinum
chemotherapy

Drug: Ara-C
chemotherapy

Drug: Dexamethasone
corticosteroide

Drug: Melphalan
chemotherapy

Drug: G-CSF
growth factor

Procedure: chemotherapy: R-CHOP
immuno-chemotherapy

Procedure: chemotherapy: R-DHAP
immuno-chemotherapy

Procedure: stem cell harvest
procedure

Procedure: total body irradiation
radiation

Procedure: high-dose chemotherapy: Ara-C /Melphalan
chemotherapy




Primary Outcome Measures :
  1. time to treatment failure after start of therapy

Secondary Outcome Measures :
  1. complete remission (CR) rate
  2. overall survival
  3. progression-free survival
  4. adverse events
  5. serious infectious complications


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Histologically proven diagnosis of mantle cell lymphoma (World Health Organization [WHO] classification)
  • 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:

  • Age > 65 years
  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00209222


Contacts
Contact: Michael Unterhalt, Dr. +49-89-7095 ext 4915 Michael.Unterhalt@med.uni-muenchen.de
Contact: Martin Dreyling, PhD +49-89-7095 ext 2202 Martin.Dreyling@med.uni-muenchen.de

Locations
France
Groupe D´Etudes des Lymphomes De l´Adulte (GELA) Recruiting
Paris, France, F-75743
Contact: Guylène Chartier    +33-1-42499811    Guylene.chartier@chu-stlouis.fr   
Contact: Olivier Hermine, PhD    +33-1-44 49 52 83    hermine@necker.fr   
Principal Investigator: Olivier Hermine, PhD         
Germany
German Low Grade Study Group (Glsg) Recruiting
Munich, Germany, D-81377
Contact: Michael Unterhalt, Dr.    +49-89-7095 ext 4915    Michael.Unterhalt@med.uni-muenchen.de   
Contact: Martin Dreyling, PhD    +49-89-7095 ext 2202    Martin.Dreyling@med.uni-muenchen.de   
Principal Investigator: Wolfgang Hiddemann, PhD         
Poland
The Maria Sklodowska Memorial, Cancer Center - Inst. of Oncology Recruiting
Warszawa, Poland, PL-02-781
Contact: Jan Walewski, MD    +48-22-546-2223    walewski@coi.waw.pl   
Contact: Marek P Nowacki, MD    +48-22-546-2223      
Principal Investigator: Jan Walewski, MD         
Sponsors and Collaborators
European Mantle Cell Lymphoma Network
German Low Grade Lymphoma Study Group
Lymphoma Study Association
Investigators
Principal Investigator: Olivier Hermine, PhD University Hospital Necker, Dept. of Adult Hematology
Study Chair: Wolfgang Hiddemann, PhD University Hospital Großhadern/LMU, Dept. of Medicine III

Publications:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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, Hänel M, Casasnovas RO, Finke J, Peter N, Bouabdallah K, Sebban C, Fischer T, Dührsen 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.

Responsible Party: Prof Dr. Martin Dreyling, University Hospital Grosshadern/European MCLNetwork
ClinicalTrials.gov Identifier: NCT00209222     History of Changes
Other Study ID Numbers: MCL2004-2
First Posted: September 21, 2005    Key Record Dates
Last Update Posted: September 10, 2012
Last Verified: July 2009

Keywords provided by European Mantle Cell Lymphoma Network:
Lymphoma, Mantle-Cell
younger patients
chemotherapy
high dose therapy
C04.557.386.480.300.725.500
C15.604.515.569.480.300.725.500
C20.683.515.761.480.300.725.500

Additional relevant MeSH terms:
Lymphoma, Mantle-Cell
Lymphoma, Non-Hodgkin
Lymphoma
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Dexamethasone
Prednisone
Cyclophosphamide
Rituximab
Doxorubicin
Etoposide
Vincristine
Melphalan
Cytarabine
Cisplatin
Anti-Inflammatory Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal
Antineoplastic Agents