AzTrials
AzTrials

Lymphoma, Mantle-CellPhase 3NCT00209222

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

A Phase 3 study testing Rituximab, Cyclophosphamide and Doxorubicin in people with Lymphoma, Mantle-Cell, run by European Mantle Cell Lymphoma Network at 3 sites in 3 countries.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
Search all trials

Trial 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… Read more about this study

Who is it for?
Ages 18 to 65 years
Conditions the study is for
Lymphoma, Mantle-Cell
What is being tested?
Rituximab, Cyclophosphamide and Doxorubicin
Type of treatment
Surgery or procedure
Could I receive a placebo?
No, everyone receives an active treatment
How many people
360 participants
Where
3 sitesin 3 countries
Study dates
Jul 2004to Dec 2014
Phase
Phase 3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 65 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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)
Show all 15Show fewer
  • 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

Trial locations and contacts

3 sites in 3 countries.

Michael Unterhalt, Dr. contact

+49-89-7095 ext. 4915

Michael.Unterhalt@med.uni-muenchen.de

Martin Dreyling, PhD contact

+49-89-7095 ext. 2202

Martin.Dreyling@med.uni-muenchen.de

3 sites in 3 countries

France1 site, 1 recruiting

  • Groupe D´Etudes des Lymphomes De l´Adulte (GELA)

    Paris, F-75743

    Guylène Chartier, +33-1-42499811, Guylene.chartier@chu-stlouis.fr

    Olivier Hermine, PhD, +33-1-44 49 52 83, hermine@necker.fr

    Recruiting

Other trials in France

Germany1 site, 1 recruiting

  • German Low Grade Study Group (Glsg)

    Munich, D-81377

    Michael Unterhalt, Dr., +49-89-7095 ext. 4915, Michael.Unterhalt@med.uni-muenchen.de

    Martin Dreyling, PhD, +49-89-7095 ext. 2202, Martin.Dreyling@med.uni-muenchen.de

    Recruiting

Other trials in Germany

Poland1 site, 1 recruiting

  • The Maria Sklodowska Memorial, Cancer Center - Inst. of Oncology

    Warsaw, PL-02-781

    Jan Walewski, MD, +48-22-546-2223, walewski@coi.waw.pl

    Marek P Nowacki, MD, +48-22-546-2223

    Recruiting

Other trials in Poland

About this 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

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.

Read the 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.

Keywords
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
Medical subject headings
Lymphoma, Mantle-Cell

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • RituximabDrug

    antibody

  • CyclophosphamideDrug

    chemotherapy

  • DoxorubicinDrug

    chemotherapy

  • VincristineDrug

    chemotherapy

  • PrednisoneDrug

    corticosteroide

  • CisplatinumDrug

    chemotherapy

  • Ara-CDrug

    chemotherapy

  • DexamethasoneDrug

    corticosteroide

  • BCNUDrug

    chemotherapy

  • MelphalanDrug

    chemotherapy

  • EtoposideDrug

    chemotherapy

  • G-CSFDrug

    growth factor

  • chemotherapy: R-CHOPProcedure or surgery

    immuno-chemotherapy

  • chemotherapy: R-DHAPProcedure or surgery

    immuno-chemotherapy

  • chemotherapy: Dexa-BEAMProcedure or surgery

    chemotherapy

  • stem cell harvestProcedure or surgery

    procedure

  • total body irradiationProcedure or surgery

    radiation

  • high-dose chemotherapy: CyclophosphamideProcedure or surgery

    chemotherapy

  • high-dose chemotherapy: Ara-C /MelphalanProcedure or surgery

    chemotherapy

Study groups in NCT00209222
Study groupRoleWhat they receive
1Active comparatorinduction: R-CHOP consoldiation : TBI/Cyclo
Receives: 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
2Experimentalinduction: R-CHOP/DHAP consolditaion: TBI/TAM
Receives: 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

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. time to treatment failure after start of therapy

Secondary outcomes (5)

  1. complete remission (CR) rate

  2. overall survival

  3. progression-free survival

  4. adverse events

  5. serious infectious complications

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted21 Sep 2005 (estimated)
  2. Study startJul 2004
  3. Primary completionDec 2014 (estimated)
  4. Study completionDec 2014 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
360 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00209222
Sponsor's protocol ID
MCL2004-2
Status last verified
Jul 2009
First submitted
13 Sep 2005
Last updated
10 Sep 2012
Results posted
No
Data monitoring committee
Yes

Publications

  • 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.

    PubMed 15591112

  • 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.

    PubMed 15668467

  • 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.

    PubMed 36469833

  • 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.

    PubMed 27313086

  • 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.

    PubMed 26022239

  • 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.

    PubMed 24687837

  • 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.

    PubMed 20032498

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Rituximab, Cyclophosphamide and Doxorubicin in people with Lymphoma, Mantle-Cell, run by European Mantle Cell Lymphoma Network at 3 sites in 3 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: status not confirmed, as of the sponsor's last update on 10 Sep 2012. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in France, Germany, Poland. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

Contact Michael Unterhalt, Dr. (+49-89-7095 ext. 4915, Michael.Unterhalt@med.uni-muenchen.de), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

time to treatment failure after start of therapy. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00209222, which also lists 7 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Sep 2012.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in