Efficacy of Upfront and Maintenance Obinutuzumab in Mantle Cell Lymphoma Treated by DHAP and MRD Driven Maintenance

NCT ID: NCT02896582

Last Updated: 2026-01-14

Study Results

Results pending

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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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

86 participants

Study Classification

INTERVENTIONAL

Study Start Date

2016-11-29

Study Completion Date

2024-12-02

Brief Summary

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This study is a multicentric, single arm phase II trial to evaluate the efficacy of upfront obinutuzumab in mantle cell lymphoma patients treated by Cisplatinum-Cytarabine-Dexamethasone (DHAP) followed by autologous transplantation plus obinutuzumab maintenance then Molecular Residual Disease (MRD) driven maintenance

Detailed Description

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Patients will be recruited over 2 years. They must have a histologically proven diagnosis of mantle cell lymphoma, be aged from 18 to 65 years at the time of registration. Patients must be eligible for autologous transplant and not previously treated for their lymphoma at inclusion. Patients will receive 4 cycles of Obinutuzumab (GA101) and Cisplatinum-Cytarabine-Dexamethasone (GA-DHAP) every 21 days followed by Autologous Stem Cell Transplant (ASCT) using a GA101-Carmustine- Etoposide- Cytarabine- Melphalan (GA-BEAM) conditioning regimen plus a Obinutuzumab maintenance for 3 years then a Obinutuzumab maintenance on demand according to MRD status. Stem cells will be collected after cycle 3 and/or 4 of GA-DHAP.

Conditions

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Mantle Cell Lymphoma

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Induction - ASCT - maintenance

Induction : 4 cycles of GA-DHAP every 21 days - Conditioning regimen and ASCT: GA-BEAM + Autologous transplantation - Maintenance : Obinutuzumab every 2 months for 3 years then every month for patients with positive MRD

Group Type EXPERIMENTAL

Obinutuzumab

Intervention Type DRUG

1000 mg D1, D8, D15 in GA-DHAP 1000 mg D-8 in GA-BEAM 1000 mg every 2 months for 3 years then every month if MRD+

Dexamethasone

Intervention Type DRUG

40 mg D1 to D4 in GA-DHAP

Aracytine

Intervention Type DRUG

2g/m² D1 \& D2 in GA-DHAP 400 mg/m² D-6 to -3 in GA-BEAM

Cisplatinum

Intervention Type DRUG

100 mg/m² D1 in GA-DHAP

Etoposide

Intervention Type DRUG

400 mg/m² D-6 to D-3 in GA-BEAM

Melphalan

Intervention Type DRUG

140 mg/m² D-2 in GA-BEAM

Carmustine

Intervention Type DRUG

300 mg/m² D-7 in GA-BEAM

Interventions

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Obinutuzumab

1000 mg D1, D8, D15 in GA-DHAP 1000 mg D-8 in GA-BEAM 1000 mg every 2 months for 3 years then every month if MRD+

Intervention Type DRUG

Dexamethasone

40 mg D1 to D4 in GA-DHAP

Intervention Type DRUG

Aracytine

2g/m² D1 \& D2 in GA-DHAP 400 mg/m² D-6 to -3 in GA-BEAM

Intervention Type DRUG

Cisplatinum

100 mg/m² D1 in GA-DHAP

Intervention Type DRUG

Etoposide

400 mg/m² D-6 to D-3 in GA-BEAM

Intervention Type DRUG

Melphalan

140 mg/m² D-2 in GA-BEAM

Intervention Type DRUG

Carmustine

300 mg/m² D-7 in GA-BEAM

Intervention Type DRUG

Other Intervention Names

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GA GA101 Cytarabine BiCNU BCNU

Eligibility Criteria

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Inclusion Criteria

* Age ≥ 18 and age ≤ 65
* Histologically confirmed (according to the World Health Organization (WHO) classification) mantle cell lymphoma. The diagnosis has to be confirmed by phenotypic expression of CD5, CD20 and cyclin D1 or the t(11;14) translocation.
* Bone marrow aspiration performed at inclusion for MRD analyses
* Eligible for autologous stem cell transplant
* Previously untreated MCL
* Stage Ann Arbor II-IV in need of treatment
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 - 2
* Life expectancy of more than 3 months
* Written informed consent
* Patient affiliated by any social security system

Exclusion Criteria

* Severe cardiac disease: York Heart Association (NYHA) grade 3-4
* Impaired liver (ALanine Amino Transferase (ALAT)/ASparagin Amino Transferase (ASAT) ≥ 2.5 Upper Limit of Normal (ULN), bilirubin ≥ 1.5 ULN), renal (calculated creatinine clearance \< 50 ml/min) or other organ function which will interfere with the treatment, if not related to lymphoma.
* History of chronic liver disease
* Hepatic veno-occlusive disease or sinusoidal obstruction syndrome
* Any of the following laboratory abnormalities, if not result of a BM infiltration:
* Absolute Neutrophils Count (ANC) \<1,500 /mm3 (1.5 x 109/L)
* Platelet counts \< 75,000/mm3 (75 x 109/L)
* Pregnancy/Nursing mothers
* Fertile men or women of childbearing potential unless:
* surgically sterile or ≥ 2 years after the onset of menopause
* willing to use a highly effective contraceptive method
* Patients with a malignancy that has been treated but not with curative intent, unless the malignancy has been in remission without treatment for ≥ 5 years prior to enrollment. Patients with a history of curatively treated basal or squamous cell carcinoma or melanoma of the skin or in situ carcinoma of the cervix are eligible.
* Known seropositivity for Human Immunodeficiency Virus (HIV), Hepatitis C Virus (HCV) or other active infection uncontrolled by treatment.
* Viral infection with hepatitis B virus (HBV) defined as hepatitis B surface antigen (HBsAg) positive and/or Hepatitis B core antibody (anti-HBc) positive Note: Patients who are immune due to hepatitis B vaccination or natural infection (HBs Ag and anti-HBc negative, anti-HBs positive) are eligible. But the patients who are immune due to hepatitis B natural infection should consult liver disease experts before start of treatment and should be monitored and managed following local medical standards to prevent hepatitis reactivation
* Prior history of Progressive Multifocal Leukoencephalopathy (PML)
* Vaccination with a live vaccine a minimum of 28 days prior to inclusion (Prolonged B cell depletion)
* History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies. Known sensitivity or allergy to murine products
* Psychiatric illness or condition which could interfere with their ability to understand the requirements of the study.
* Person deprived of his/her liberty by a judicial or administrative decision
* Person hospitalized without consent
* Adult person under legal protection
Minimum Eligible Age

18 Years

Maximum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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The Lymphoma Academic Research Organisation

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Steven Le Gouill, Pr

Role: PRINCIPAL_INVESTIGATOR

Nantes University Hospital

Olivier Hermine, Pr

Role: PRINCIPAL_INVESTIGATOR

Hopital Necker - Paris

Locations

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CHU d'Amiens

Amiens, , France

Site Status

CHU d'Angers

Angers, , France

Site Status

CH d'Avignon

Avignon, , France

Site Status

CHU de Caen

Caen, , France

Site Status

CHU de Clermont Ferrand

Clermont-Ferrand, , France

Site Status

Hopital Henri Mondor

Créteil, , France

Site Status

CHU de Dijon - Hôpital le Bocage

Dijon, , France

Site Status

CHU de Grenoble

Grenoble, , France

Site Status

CHD Vendée

La Roche-sur-Yon, , France

Site Status

Clinique Victor Hugo

Le Mans, , France

Site Status

CHRU Lille - Hôpital Claude Huriez

Lille, , France

Site Status

CHU Limoges

Limoges, , France

Site Status

CHU Montpellier

Montpellier, , France

Site Status

CHU Nantes

Nantes, , France

Site Status

Hôpital Saint Louis

Paris, , France

Site Status

APHP - Hopital Necker

Paris, , France

Site Status

CH Perpignan

Perpignan, , France

Site Status

CHU de Haut Leveque

Pessac, , France

Site Status

CHU Lyon Sud

Pierre-Bénite, , France

Site Status

CHU de Poitiers

Poitiers, , France

Site Status

Centre Hospitalier Annecy-Genevois

Pringy, , France

Site Status

CHU Robert Debré

Reims, , France

Site Status

CHU Pontchaillou

Rennes, , France

Site Status

Centre Henri Becquerel

Rouen, , France

Site Status

Institut de Cancérologie de Loire

Saint-Priest-en-Jarez, , France

Site Status

CHU de Strasbourg

Strasbourg, , France

Site Status

I.U.C.T Oncopole

Toulouse, , France

Site Status

CHRU Bretonneau

Tours, , France

Site Status

CHU de Brabois

Vandœuvre-lès-Nancy, , France

Site Status

Gustave Roussy Cancer Campus

Villejuif, , France

Site Status

Countries

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France

References

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Sarkozy C, Callanan M, Thieblemont C, Oberic L, Burroni B, Bouabdallah K, Damaj G, Tessoulin B, Ribrag V, Houot R, Morschhauser F, Griolet S, Joubert C, Cacheux V, Delwail V, Safar V, Gressin R, Cheminant M, Delfau-Larue MH, Hermine O, Macintyre E, Le Gouill S. Obinutuzumab vs rituximab for transplant-eligible patients with mantle cell lymphoma. Blood. 2024 Jul 18;144(3):262-271. doi: 10.1182/blood.2024023944.

Reference Type DERIVED
PMID: 38669626 (View on PubMed)

Bodet-Milin C, Morvant C, Carlier T, Frecon G, Tournilhac O, Safar V, Kraeber-Bodere F, Le Gouill S, Macintyre E, Bailly C. Performance of baseline FDG-PET/CT radiomics for prediction of bone marrow minimal residual disease status in the LyMa-101 trial. Sci Rep. 2023 Oct 24;13(1):18177. doi: 10.1038/s41598-023-45215-y.

Reference Type DERIVED
PMID: 37875524 (View on PubMed)

Le Gouill S, Beldi-Ferchiou A, Alcantara M, Cacheux V, Safar V, Burroni B, Guidez S, Gastinne T, Canioni D, Thieblemont C, Maisonneuve H, Bodet-Milin C, Houot R, Oberic L, Bouabdallah K, Bescond C, Damaj G, Jaccard A, Daguindau N, Moreau A, Tilly H, Ribrag V, Delfau-Larue MH, Hermine O, Macintyre E. Molecular response after obinutuzumab plus high-dose cytarabine induction for transplant-eligible patients with untreated mantle cell lymphoma (LyMa-101): a phase 2 trial of the LYSA group. Lancet Haematol. 2020 Nov;7(11):e798-e807. doi: 10.1016/S2352-3026(20)30291-X. Epub 2020 Sep 21.

Reference Type DERIVED
PMID: 32971036 (View on PubMed)

Bailly C, Carlier T, Berriolo-Riedinger A, Casasnovas O, Gyan E, Meignan M, Moreau A, Burroni B, Djaileb L, Gressin R, Devillers A, Lamy T, Thieblemont C, Hermine O, Kraeber-Bodere F, Le Gouill S, Bodet-Milin C. Prognostic value of FDG-PET in patients with mantle cell lymphoma: results from the LyMa-PET Project. Haematologica. 2020 Jan;105(1):e33-e36. doi: 10.3324/haematol.2019.223016. Epub 2019 Aug 1. No abstract available.

Reference Type DERIVED
PMID: 31371411 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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LyMa101

Identifier Type: -

Identifier Source: org_study_id

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