Home
Search
Study Topics
Glossary
|
|
|
|
|
Sponsors and Collaborators: |
European Mantle Cell Lymphoma Network German Low Grade Lymphoma Study Group Groupe d'Etudes de Lymphomes de L'Adulte |
---|---|
Information provided by: | European Mantle Cell Lymphoma Network |
ClinicalTrials.gov Identifier: | NCT00209222 |
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 | Intervention | 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 III |
Study Type: | Interventional |
Study Design: | Treatment, Randomized, Open Label, Active Control, Parallel Assignment, Efficacy Study |
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 |
Estimated Enrollment: | 360 |
Study Start Date: | July 2004 |
Estimated Study Completion Date: | June 2010 |
Estimated Primary Completion Date: | January 2010 (Final data collection date for primary outcome measure) |
Arms | Assigned Interventions |
---|---|
1: Active Comparator
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
|
2: Experimental
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
|
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.
Ages Eligible for Study: | 18 Years to 65 Years |
Genders Eligible for Study: | Both |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
Exclusion Criteria:
Serious disease interfering with a regular therapy according to the study protocol:
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 |
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 |
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 |
Responsible Party: | University Hospital Grosshadern/European MCLNetwork ( Prof Dr. Martin Dreyling ) |
Study ID Numbers: | MCL2004-2 |
Study First Received: | September 13, 2005 |
Last Updated: | May 9, 2008 |
ClinicalTrials.gov Identifier: | NCT00209222 History of Changes |
Health Authority: | Germany: Federal Institute for Drugs and Medical Devices |
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 |
Anti-Inflammatory Agents Antimetabolites Dexamethasone Prednisone Melphalan Immunologic Factors Hormone Antagonists Lymphoma, Mantle-Cell Hormones, Hormone Substitutes, and Hormone Antagonists Antiemetics Mantle Cell Lymphoma Cyclophosphamide Hormones Etoposide phosphate Anti-Bacterial Agents |
Cisplatin Mitogens Alkylating Agents Lymphoma Etoposide Dexamethasone acetate Cytarabine Immunoglobulins Immunoproliferative Disorders Antineoplastic Agents, Hormonal Rituximab Vincristine Antimitotic Agents Glucocorticoids Antiviral Agents |
Dexamethasone Anti-Inflammatory Agents Prednisone Anti-Infective Agents Antimetabolites, Antineoplastic Molecular Mechanisms of Pharmacological Action Lymphoma, Mantle-Cell Physiological Effects of Drugs Hormones, Hormone Substitutes, and Hormone Antagonists Antiemetics Hormones Therapeutic Uses Immunoproliferative Disorders Immune System Diseases Antineoplastic Agents, Hormonal |
Rituximab Vincristine Glucocorticoids Doxorubicin Neoplasms Lymphoma, Non-Hodgkin Antineoplastic Agents, Phytogenic Antimetabolites Melphalan Immunologic Factors Antineoplastic Agents Cyclophosphamide Antibiotics, Antineoplastic Cisplatin Lymphoma |