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
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
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
86
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+
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
CHU d'Amiens
Amiens, France
Molecular Residual Disease (MRD) in bone marrow after 4 cycles of GA-DHAP
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
Time frame: 4 cycles (1 cycle is 21 days)
Response according to Cheson 99
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)
Time frame: 5.5 years (2.5 years of treatment and 3 years of maintenance)
Overall response rate (ORR)
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)
Time frame: 5.5 years (2.5 years of treatment and 3 years of maintenance)
Positron Emission Tomography (PET) result
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).
Time frame: 5.5 years (2.5 years of treatment and 3 years of maintenance)
MRD
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.
Time frame: 5.5 years (2.5 years of treatment and 3 years of maintenance)
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
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
CHU d'Angers
Angers, France
CH d'Avignon
Avignon, France
CHU de Caen
Caen, France
CHU de Clermont Ferrand
Clermont-Ferrand, France
Hopital Henri Mondor
Créteil, France
CHU de Dijon - Hôpital le Bocage
Dijon, France
CHU de Grenoble
Grenoble, France
CHD Vendée
La Roche-sur-Yon, France
Clinique Victor Hugo
Le Mans, France
...and 20 more locations
MRD and after maintenance "on demand"
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.
Time frame: 8.5 years (2.5 years of treatment and 2x3 years of maintenance)
Progression Free Survival (PFS)
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.
Time frame: 8.5 years (2.5 years of treatment and 2x3 years of maintenance)
Overall survival (OS)
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
Time frame: 8.5 years (2.5 years of treatment and 2x3 years of maintenance)
Number of patients for whom stemm cell collection will fail
Stem cell collection failure will be evaluated after induction treatment
Time frame: 3 years
Duration of MRD negativity
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.
Time frame: 8.5 years (2.5 years of treatment and 2x3 years of maintenance)
Treatment duration
Time frame: 9 years
Average dose
Time frame: 9 years
Number of premature treatment discontinuation
Time frame: 9 years
Frequency of premature treatment discontinuation
Time frame: 9 years
Number of study discontinuation
Time frame: 9 years
Frequency of study discontinuation
Time frame: 9 years
Number of adverse events
Time frame: 9 years