- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02896582
Efficacy of Upfront and Maintenance Obinutuzumab in Mantle Cell Lymphoma Treated by DHAP and MRD Driven Maintenance (LyMa101)
March 13, 2024 updated by: The Lymphoma Academic Research Organisation
Phase II Study to Evaluate the Efficacy of Upfront Obinutuzumab in Mantle Cell Lymphoma Patients Treated by DHAP Followed by Autologous Transplantation Plus Obinutuzumab Maintenance Then MRD Driven Maintenance
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
Study Overview
Status
Active, not recruiting
Conditions
Intervention / Treatment
Detailed Description
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.
Study Type
Interventional
Enrollment (Actual)
86
Phase
- Phase 2
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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Amiens, France, 80480
- CHU d'Amiens
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Angers, France, 49000
- CHU d'Angers
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Avignon, France, 84902
- CH d'Avignon
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Caen, France, 14033
- CHU de Caen
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Clermont Ferrand, France, 63000
- CHU de Clermont Ferrand
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Créteil, France, 94010
- Hôpital Henri Mondor
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Dijon, France, 21034
- CHU de Dijon - Hopital le Bocage
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Grenoble, France, 38700
- CHU de Grenoble
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La Roche sur Yon, France, 85925
- CHD Vendee
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Le Mans, France, 72000
- Clinique Victor Hugo
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Lille, France, 59037
- CHRU LILLE - Hôpital Claude Huriez
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Limoges, France, 87042
- CHU Limoges
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Montpellier, France, 34295
- CHU Montpellier
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Nantes, France, 44093
- CHU Nantes
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Paris, France, 75475
- Hôpital Saint Louis
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Paris, France, 75743
- APHP - Hopital Necker
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Perpignan, France, 66046
- Ch Perpignan
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Pessac, France, 33604
- CHU de Haut Leveque
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Pierre Bénite, France, 69130
- CHU Lyon Sud
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Poitiers, France, 86021
- CHU De Poitiers
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Pringy, France, 74374
- Centre Hospitalier Annecy-Genevois
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Reims, France, 51092
- CHU Robert Debré
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Rennes, France, 35033
- CHU Pontchaillou
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Rouen, France, 76038
- Centre Henri Becquerel
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Saint priest en Jarez, France, 42271
- Institut de Cancérologie de Loire
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Strasbourg, France, 67091
- CHU de Strasbourg
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Toulouse, France, 31100
- I.U.C.T Oncopole
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Tours, France, 37044
- CHRU Bretonneau
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Vandoeuvre les Nancy, France
- CHU de Brabois
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Villejuif, France, 94805
- Gustave Roussy Cancer Campus
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years to 65 years (Adult, Older Adult)
Accepts Healthy Volunteers
No
Description
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
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: 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
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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+
Other Names:
40 mg D1 to D4 in GA-DHAP
2g/m² D1 & D2 in GA-DHAP 400 mg/m² D-6 to -3 in GA-BEAM
Other Names:
100 mg/m² D1 in GA-DHAP
400 mg/m² D-6 to D-3 in GA-BEAM
140 mg/m² D-2 in GA-BEAM
300 mg/m² D-7 in GA-BEAM
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Molecular Residual Disease (MRD) in bone marrow after 4 cycles of GA-DHAP
Time Frame: 4 cycles (1 cycle is 21 days)
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to evaluate the efficacy of upfront Obinutuzumab (GA101) at the molecular level (MRD) in bone marrow after induction in patients with previously untreated Mantle Cell Lymphoma (MCL) treated by DHAP
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4 cycles (1 cycle is 21 days)
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Response according to Cheson 99
Time Frame: 5.5 years (2.5 years of treatment and 3 years of maintenance)
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Response after 2.5 years of treatment and 3 years of maintenance will be evaluated.
Assessment of response will be based on the International Workshop to Standardize Response criteria for Non Hodgkin Lymphoma (NHL) (Criteria for evaluation of response in Non-Hodgkin's lymphoma (Cheson, 1999)
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5.5 years (2.5 years of treatment and 3 years of maintenance)
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Overall response rate (ORR)
Time Frame: 5.5 years (2.5 years of treatment and 3 years of maintenance)
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Response after 2.5 years of treatment and 3 years of maintenance will be evaluated.
Assessment of response will be based on the International Workshop to Standardize Response criteria for NHL (Criteria for evaluation of response in Non-Hodgkin's lymphoma (Cheson, 1999)
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5.5 years (2.5 years of treatment and 3 years of maintenance)
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Positron Emission Tomography (PET) result
Time Frame: 5.5 years (2.5 years of treatment and 3 years of maintenance)
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PET result after 2.5 years of treatment and 3 years of maintenance will be evaluated.
Assessment of PET will be based on Lugano 2014 criteria (according to Cheson & al.
Journal of Clinical Oncology 2015).
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5.5 years (2.5 years of treatment and 3 years of maintenance)
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MRD
Time Frame: 5.5 years (2.5 years of treatment and 3 years of maintenance)
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Molecular residual disease (MRD) after 2.5 years of treatment and 3 years of maintenance will be evaluated.
Assessment of MRD will be based on molecular level in bone marrow (BM) according to the European Mantle Cell Lymphoma network (EU-MCL) guidelines.
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5.5 years (2.5 years of treatment and 3 years of maintenance)
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MRD and after maintenance "on demand"
Time Frame: 8.5 years (2.5 years of treatment and 2x3 years of maintenance)
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Molecular residual disease (MRD) after maintenance "on demand" will be evaluated.
Assessment of MRD will be based on molecular level in BM according to EU MCL network guidelines.
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8.5 years (2.5 years of treatment and 2x3 years of maintenance)
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Progression Free Survival (PFS)
Time Frame: 8.5 years (2.5 years of treatment and 2x3 years of maintenance)
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PFS is defined as the time from inclusion into the study to the first observation of documented disease progression or death due to any cause.
If a subject has not progressed or died, PFS will be censored at the time of last visit with adequate assessment.
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8.5 years (2.5 years of treatment and 2x3 years of maintenance)
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Overall survival (OS)
Time Frame: 8.5 years (2.5 years of treatment and 2x3 years of maintenance)
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OS will be measured from the date of inclusion to the date of death from any cause.
Alive patients will be censored at their last contact date
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8.5 years (2.5 years of treatment and 2x3 years of maintenance)
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Number of patients for whom stemm cell collection will fail
Time Frame: 3 years
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Stem cell collection failure will be evaluated after induction treatment
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3 years
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Duration of MRD negativity
Time Frame: 8.5 years (2.5 years of treatment and 2x3 years of maintenance)
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Duration of MRD negativity is defined as the time from the date of attainment the first negative MRD to the date of positive MRD.
Duration or MRD negativity would be assessed for patients with at least one MRD negativity and as survival endpoint.
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8.5 years (2.5 years of treatment and 2x3 years of maintenance)
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Treatment duration
Time Frame: 9 years
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9 years
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Average dose
Time Frame: 9 years
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9 years
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Number of premature treatment discontinuation
Time Frame: 9 years
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9 years
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Frequency of premature treatment discontinuation
Time Frame: 9 years
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9 years
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Number of study discontinuation
Time Frame: 9 years
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9 years
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Frequency of study discontinuation
Time Frame: 9 years
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9 years
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Number of adverse events
Time Frame: 9 years
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9 years
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Investigators
- Principal Investigator: Olivier Hermine, Pr, Hopital Necker - Paris
- Principal Investigator: Steven Le Gouill, Pr, Nantes University Hospital
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
General Publications
- 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.
- 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.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
October 1, 2016
Primary Completion (Actual)
March 1, 2019
Study Completion (Estimated)
March 1, 2025
Study Registration Dates
First Submitted
September 6, 2016
First Submitted That Met QC Criteria
September 6, 2016
First Posted (Estimated)
September 12, 2016
Study Record Updates
Last Update Posted (Actual)
March 15, 2024
Last Update Submitted That Met QC Criteria
March 13, 2024
Last Verified
March 1, 2024
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Immune System Diseases
- Neoplasms by Histologic Type
- Neoplasms
- Lymphoproliferative Disorders
- Lymphatic Diseases
- Immunoproliferative Disorders
- Lymphoma, Non-Hodgkin
- Lymphoma
- Lymphoma, Mantle-Cell
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Anti-Infective Agents
- Autonomic Agents
- Peripheral Nervous System Agents
- Antiviral Agents
- Enzyme Inhibitors
- Anti-Inflammatory Agents
- Antimetabolites, Antineoplastic
- Antimetabolites
- Antineoplastic Agents
- Immunosuppressive Agents
- Immunologic Factors
- Antiemetics
- Gastrointestinal Agents
- Glucocorticoids
- Hormones
- Hormones, Hormone Substitutes, and Hormone Antagonists
- Antineoplastic Agents, Hormonal
- Antineoplastic Agents, Alkylating
- Alkylating Agents
- Myeloablative Agonists
- Antineoplastic Agents, Phytogenic
- Topoisomerase II Inhibitors
- Topoisomerase Inhibitors
- Antineoplastic Agents, Immunological
- Dexamethasone
- Etoposide
- Cisplatin
- Melphalan
- Cytarabine
- Obinutuzumab
- Carmustine
Other Study ID Numbers
- LyMa101
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
NO
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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