Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
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

Tracking Information
First Submitted Date  ICMJE September 13, 2005
First Posted Date  ICMJE September 21, 2005
Last Update Posted Date September 10, 2012
Study Start Date  ICMJE July 2004
Estimated Primary Completion Date December 2014   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 13, 2005)
time to treatment failure after start of therapy
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: March 24, 2006)
  • complete remission (CR) rate
  • overall survival
  • progression-free survival
  • adverse events
  • serious infectious complications
Original Secondary Outcome Measures  ICMJE
 (submitted: September 13, 2005)
  • CR rate
  • overall survival
  • progression-free survival
  • adverse events
  • serious infectious complications
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Efficacy of R-CHOP vs R-CHOP/R-DHAP in Untreated MCL
Official Title  ICMJE 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
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.
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  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Lymphoma, Mantle-Cell
Intervention  ICMJE
  • 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: BCNU
    chemotherapy
  • Drug: Melphalan
    chemotherapy
  • Drug: Etoposide
    chemotherapy
  • Drug: G-CSF
    growth factor
  • Procedure: chemotherapy: R-CHOP
    immuno-chemotherapy
  • Procedure: chemotherapy: R-DHAP
    immuno-chemotherapy
  • Procedure: chemotherapy: Dexa-BEAM
    chemotherapy
  • Procedure: stem cell harvest
    procedure
  • Procedure: total body irradiation
    radiation
  • Procedure: high-dose chemotherapy: Cyclophosphamide
    chemotherapy
  • Procedure: high-dose chemotherapy: Ara-C /Melphalan
    chemotherapy
Study Arms  ICMJE
  • Active Comparator: 1
    induction: R-CHOP consoldiation : TBI/Cyclo
    Interventions:
    • Drug: Rituximab
    • Drug: Cyclophosphamide
    • Drug: Doxorubicin
    • Drug: Vincristine
    • Drug: Prednisone
    • Drug: BCNU
    • Drug: Melphalan
    • Drug: Etoposide
    • Drug: G-CSF
    • Procedure: chemotherapy: R-CHOP
    • Procedure: chemotherapy: Dexa-BEAM
    • Procedure: stem cell harvest
    • Procedure: total body irradiation
    • Procedure: high-dose chemotherapy: Cyclophosphamide
  • Experimental: 2
    induction: R-CHOP/DHAP consolditaion: TBI/TAM
    Interventions:
    • Drug: Rituximab
    • Drug: Cyclophosphamide
    • Drug: Doxorubicin
    • Drug: Vincristine
    • Drug: Prednisone
    • Drug: Cisplatinum
    • Drug: Ara-C
    • Drug: Dexamethasone
    • Drug: Melphalan
    • Drug: G-CSF
    • Procedure: chemotherapy: R-CHOP
    • Procedure: chemotherapy: R-DHAP
    • Procedure: stem cell harvest
    • Procedure: total body irradiation
    • Procedure: high-dose chemotherapy: Ara-C /Melphalan
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Unknown status
Estimated Enrollment  ICMJE
 (submitted: September 13, 2005)
360
Original Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 2014
Estimated Primary Completion Date December 2014   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 65 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE France,   Germany,   Poland
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00209222
Other Study ID Numbers  ICMJE MCL2004-2
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Prof Dr. Martin Dreyling, University Hospital Grosshadern/European MCLNetwork
Study Sponsor  ICMJE European Mantle Cell Lymphoma Network
Collaborators  ICMJE
  • German Low Grade Lymphoma Study Group
  • Lymphoma Study Association
Investigators  ICMJE
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
PRS Account European Mantle Cell Lymphoma Network
Verification Date July 2009

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP