This study will determine the Maximal Tolerated Dose if any and the recommended dose for phase 2 of monalizumab, a monoclonal antibody directed against the CD94/NKG2A receptor, after allogenic stem cell transplantation. All patients will receive one single intravenous administration of one of the four doses of monalizumab.
Allogeneic hematopoietic stem cell transplantation (Allo-HSCT) is a curative option for most of hematological malignancies, though the graft-versus-tumor (GVT) effect mediated by immune cells from the donor. However, the use of Allo-HSCT is limited by its toxicity, notably the graft-versus-host disease (GVHD) that is a major cause of non-relapse mortality (NRM). Conditioning regimens dramatically improved during the last fifteen years, with a decrease of both GVHD and NRM rates. Now, disease recurrence after Allo-HSCT is the first cause of treatment failure and remains a concern for approximately 30% of the patients. Based on a safety immunologic platform (ATG based reduced toxicity conditioning regimens), it is needed to develop post Allo-HSCT strategies to decrease the incidence of relapse. In this context, the modulation of immune cell activity could play a role to prevent relapse. NK cells have a unique capacity to exert potent GVT effects without inducing GVHD. Moreover, NK cells recovery occurs early after Allo-HSCT and NK cells function are not severely impaired by the use of ciclosporin A, that is given for few months after Allo-HSCT as GVHD prophylaxis. Thus, NK cell modulation appears as a viable option for early immune intervention after Allo-HSCT. Monalizumab (IPH2201), a monoclonal antibody has a non-depleting and purely blocking activity directed with high affinity and specificity against the CD94/NKG2A receptor expressed by subsets of NK cells, activated αβ CD8+ T cells, γδ-T cells and NK T cells. By suppressing the inhibitory signal transduced by NKG2A, IPH2201 enhances the anti-tumor functions, including cytolytic activity of these immune effector cells.The aim of the study is to determine the safety of IPH2201 after allogenic stem cell transplantation.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
18
Four dose levels will be tested.
Institut Paoli Calmettes
Marseille, Bouches Du Rhônes, France
RECRUITINGOccurence ratio of dose-limiting toxicity (DLT)
The occurrence of any of these 3 events will lead to the reporting of a Dose Limiting Toxicity: * Any Grade ≥ 3 toxicity according to CTCAE attributable to IPH2201 administration, occurring within 4 weeks of IPH2201 administration and considered as relevant by the investigator * Any grade ≥ II acute GVHD requiring a treatment by systemic corticosteroids and occurring within 4 weeks of IPH2201 administration. * Any grade ≥ moderate chronic GVHD occurring within 4 weeks of IPH2201 administration.
Time frame: 4 weeks
Incidence of acute GVHD of each grade or chronic GVHD of each degree of severity
Safety will be assessed using Glucksberg's classification for acute Graft versus host disease (GVHD) and NIH classification for chronic GVHD.
Time frame: from D0 to Week 26 after administration of IPH2201 and at 1 year after transplantation
Probabilities of non-relapse mortality (NRM)
Time frame: 1 year after the administration of IPH2201
Cumulative incidence of relapse (CIR)
Efficacy endpoint
Time frame: 1 year after administration of IPH2201.
Probability of Disease Free Survival (DFS)
Efficacy endpoint
Time frame: 1 year after the administration of IPH2201
Probability of Overall survival (OS)
Efficacy endpoint
Time frame: 1 year after the administration of IPH2201
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