NCT02921685

Brief Summary

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.

Trial Health

43
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
18

participants targeted

Target at P25-P50 for phase_1

Timeline
Completed

Started Nov 2016

Typical duration for phase_1

Geographic Reach
1 country

1 active site

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

September 27, 2016

Completed
6 days until next milestone

First Posted

Study publicly available on registry

October 3, 2016

Completed
2 months until next milestone

Study Start

First participant enrolled

November 28, 2016

Completed
2.5 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

May 28, 2019

Completed
11 months until next milestone

Study Completion

Last participant's last visit for all outcomes

April 28, 2020

Completed
Last Updated

September 19, 2018

Status Verified

September 1, 2018

Enrollment Period

2.5 years

First QC Date

September 27, 2016

Last Update Submit

September 18, 2018

Conditions

Hematologic Malignancies

Outcome Measures

Primary Outcomes (1)

  • Occurence 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.

    4 weeks

Secondary Outcomes (5)

  • Incidence of acute GVHD of each grade or chronic GVHD of each degree of severity

    from D0 to Week 26 after administration of IPH2201 and at 1 year after transplantation

  • Probabilities of non-relapse mortality (NRM)

    1 year after the administration of IPH2201

  • Cumulative incidence of relapse (CIR)

    1 year after administration of IPH2201.

  • Probability of Disease Free Survival (DFS)

    1 year after the administration of IPH2201

  • Probability of Overall survival (OS)

    1 year after the administration of IPH2201

Study Arms (1)

Monalizumab

EXPERIMENTAL

Monalizumab treatment will be initiated 75 to 100 days after hematopoietic stem cells transplantation. Patients will receive a single dose of monalizumab by intravenous route over 1 hour.

Drug: Monalizumab

Interventions

MonalizumabDRUG

Four dose levels will be tested.

Also known as: anti CD94/NKG2A, IPH2201
Monalizumab

Eligibility Criteria

Age18 Years - 70 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Patients presenting a hematological malignancy (acute myeloid leukemia, acute lymphoblastic leukemia, High risk R-IPSS myelodysplastic syndromes, multiple myeloma, chronic lymphoid leukemia, chronic myeloid leukemia, myeloproliferative neoplasm, Hodgkin lymphoma or Non-Hodgkin lymphoma) treated by allogeneic HSCT according to the following parameters :
  • Donor : HLA matched related or unrelated (10/10) donor
  • Graft : peripheral blood stem cells
  • Conditioning : All types of conditioning reduced toxicity conditioning regimens ATG as in-vivo T-cell depletion
  • Acute myeloid leukemia (AML) or acute lymphoblastic leukemia (ALL) patients: in morphological complete remission (CR) with less than 5% bone marrow blast count.
  • High risk R-IPSS myelodysplastic syndromes patients: with at least marrow CR with less than 5% marrow blast count.
  • Multiple myeloma patients: in at least very good partial response.
  • Chronic Lymphoid Leukemia patients: in CR.
  • Chronic Myeloid Leukemia patients: in hematological CR.
  • Myeloproliferative neoplasm patients: no criteria for disease in acceleration phase.
  • Hodgkin lymphoma or Non-Hodgkin lymphoma patients: in CR.
  • Age ≥ 18 and ≤ 70 years
  • ECOG = 0-1 or Karnofsky index ≥ 70%
  • Clinical laboratory values at screening
  • Calculated creatinine clearance (according to MDRD) \> 50 ml/min/1.73 m2
  • +21 more criteria

You may not qualify if:

  • Any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule.
  • Pregnant or lactating women

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Institut Paoli Calmettes

Marseille, Bouches Du Rhônes, 13009, France

RECRUITING

Related Publications (4)

  • Ruggeri L, Urbani E, Andre P, Mancusi A, Tosti A, Topini F, Blery M, Animobono L, Romagne F, Wagtmann N, Velardi A. Effects of anti-NKG2A antibody administration on leukemia and normal hematopoietic cells. Haematologica. 2016 May;101(5):626-33. doi: 10.3324/haematol.2015.135301. Epub 2015 Dec 31.

    PMID: 26721894BACKGROUND

  • Godal R, Bachanova V, Gleason M, McCullar V, Yun GH, Cooley S, Verneris MR, McGlave PB, Miller JS. Natural killer cell killing of acute myelogenous leukemia and acute lymphoblastic leukemia blasts by killer cell immunoglobulin-like receptor-negative natural killer cells after NKG2A and LIR-1 blockade. Biol Blood Marrow Transplant. 2010 May;16(5):612-21. doi: 10.1016/j.bbmt.2010.01.019. Epub 2010 Feb 6.

    PMID: 20139023BACKGROUND

  • Rathmann S, Glatzel S, Schonberg K, Uhrberg M, Follo M, Schulz-Huotari C, Kaymer M, Veelken H, Finke J, Fisch P. Expansion of NKG2A-LIR1- natural killer cells in HLA-matched, killer cell immunoglobulin-like receptors/HLA-ligand mismatched patients following hematopoietic cell transplantation. Biol Blood Marrow Transplant. 2010 Apr;16(4):469-81. doi: 10.1016/j.bbmt.2009.12.008. Epub 2010 Jan 4.

    PMID: 20044012BACKGROUND

  • Pical-Izard C, Crocchiolo R, Granjeaud S, Kochbati E, Just-Landi S, Chabannon C, Frassati C, Picard C, Blaise D, Olive D, Fauriat C. Reconstitution of natural killer cells in HLA-matched HSCT after reduced-intensity conditioning: impact on clinical outcome. Biol Blood Marrow Transplant. 2015 Mar;21(3):429-39. doi: 10.1016/j.bbmt.2014.11.681. Epub 2015 Jan 9.

    PMID: 25579888BACKGROUND

Related Links

MeSH Terms

Conditions

Hematologic Neoplasms

Interventions

monalizumab

Condition Hierarchy (Ancestors)

Neoplasms by SiteNeoplasmsHematologic DiseasesHemic and Lymphatic Diseases

Study Officials

  • Didier BLAISE, MD, PhD

    Institut Paoli-Calmettes

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Dominique GENRE, MD

CONTACT

33 4 91 22 37 78genred@ipc.unicancer.fr

Margot BERLINE, MSc, MBA

CONTACT

33 4 91 22 37 78boqueti@ipc.unicancer.fr

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

September 27, 2016

First Posted

October 3, 2016

Study Start

November 28, 2016

Primary Completion

May 28, 2019

Study Completion

April 28, 2020

Last Updated

September 19, 2018

Record last verified: 2018-09

Locations

FR(1)