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Hematologic MalignanciesPhase 1PIRATNCT02921685

Study of a Humanized Antibody Initiated 2 Months After an HLA Matched Allogenic Stem Cell Transplantation

A Phase 1 study testing Monalizumab in people with Hematologic Malignancies, run by Institut Paoli-Calmettes at 1 site in France.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 to 70 years
Conditions the study is for
Hematologic Malignancies
What is being tested?
Monalizumab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
18 participants
Where
1 siteFrance
Study dates
28 Nov 2016to 28 Apr 2020
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 70 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
  • GVHD prophylaxis by cyclosporine, still ongoing at full dose at the time of the inclusion
  • Patient being in one of the following post-graft situation at the time of inclusion:
Show all 42Show fewer
  • 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
  • Independence of red blood cell transfusion
  • Platelet count > 75 x 109/l
  • ANC > 1 x 109/l
  • Bilirubin < 1.5 ULN
  • ALT and AST < 3 ULN
  • Patients (male or female) who accept and are able to use contraceptive methods recognized as highly effective throughout the study and up to 5 months after the drug administration
  • Signed informed consent of the current clinical study, prior to any protocol-specific procedure
  • Patient affiliated to the national "Social Security" regimen or beneficiary of this regimen
  • Non inclusion Criteria:
  • Previous history of grade ≥ II acute GVHD (Glucksberg classification)
  • Current active disease or positive serology for HIV before grafting, and/or HCV with detectable viremia and/ or HBV with positive Hbs Antigen.
  • Abnormal cardiac status with any of the following :
  • Ejection fraction (measured by ultrasound or radionuclide imaging) < 50%
  • Unstable angina
  • Myocardial infarction within the last 6 months
  • Presence or persistence of documented congestive heart failure (New York Heart Association functional classification III-IV)
  • Arrhythmia requiring treatment and which is not stabilized by the treatment.
  • QTc ≥ 450 ms (M) or 470 ms (F) (Bazett formula)
  • Previous other allogeneic hematopoietic transplantation or solid organ transplantation
  • Any other serious concurrent uncontrolled medical disorder within 4 weeks prior to IPH2201 administration
  • Use of systemic corticosteroids ongoing or within the last 1 week prior IPH2201 admin-istration
  • Use of any investigational agent within 3 months prior to first dosing (except procedure of conditioning regimen including registered drugs combinations, i.e. Busulfan and Fludarabine or Busulfan and Endoxan)
  • History of another malignancy (except, basal cell carcinoma of the skin, or in situ cervix carcinoma, or any other malignancy in complete remission for more than 3 years since the completion of the treatment). However in the case of leukemia or MDS a previous malignancy accountable for the present disease will not be an exclusion criteria if in complete remission for more than 2 years
  • Any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule.
  • Pregnant or lactating women

Who cannot join

None listed.

Trial locations and contacts

1 site in 1 country.

Dominique GENRE, MD contact

33 4 91 22 37 78

genred@ipc.unicancer.fr

Margot BERLINE, MSc, MBA contact

33 4 91 22 37 78

boqueti@ipc.unicancer.fr

France1 site, 1 recruiting

  • Institut Paoli Calmettes

    Marseille, Bouches Du Rhônes, 13009

    Dominique GENRE, MD, 33 4 91 22 37 78, genred@ipc.unicancer.fr

    Isabelle BOQUET, PhD, 33 4 91 22 37 78, boqueti@ipc.unicancer.fr

    Recruiting

Other trials in France

About this study

Official title: A Phase 1 Study of MONALIZUMAB (IPH2201), a Humanized Anti CD94/NKG2A Monoclonal Antibody (Mab) Initiated 2 Months After an HLA Matched Allogenic Stem Cell Transplantation (SCT) Prepared With a Reduced Intensity Conditioning

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.

Read the detailed description

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.

Being tested
Monalizumab
Medical subject headings
Hematologic Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • MonalizumabDrug

    Also called anti CD94/NKG2A, IPH2201

    Four dose levels will be tested.

Study groups in NCT02921685
Study groupRoleWhat they receive
MonalizumabExperimentalMonalizumab 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.
Receives: Drug: Monalizumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: 4 weeks

Secondary outcomes (5)

  1. 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.

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

  2. Probabilities of non-relapse mortality (NRM)

    Measured: 1 year after the administration of IPH2201

  3. Cumulative incidence of relapse (CIR)

    Efficacy endpoint

    Measured: 1 year after administration of IPH2201.

  4. Probability of Disease Free Survival (DFS)

    Efficacy endpoint

    Measured: 1 year after the administration of IPH2201

  5. Probability of Overall survival (OS)

    Efficacy endpoint

    Measured: 1 year after the administration of IPH2201

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted3 Oct 2016 (estimated)
  2. Study start28 Nov 2016
  3. Primary completion28 May 2019 (estimated)
  4. Study completion28 Apr 2020 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
18 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02921685
Sponsor's protocol ID
PIRAT-IPC 2015-018
Acronym
PIRAT
Status last verified
Sep 2018
First submitted
27 Sep 2016
Last updated
19 Sep 2018
Results posted
No
Data monitoring committee
Yes

Publications

  • 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.

    PubMed 26721894

  • 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.

    PubMed 20139023

  • 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.

    PubMed 20044012

  • 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.

    PubMed 25579888

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Monalizumab in people with Hematologic Malignancies, run by Institut Paoli-Calmettes at 1 site in France.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 42 inclusion and 0 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: status not confirmed, as of the sponsor's last update on 19 Sep 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

Contact Dominique GENRE, MD (33 4 91 22 37 78, genred@ipc.unicancer.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Occurence ratio of dose-limiting toxicity (DLT) (time frame: 4 weeks). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02921685, which also lists 4 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Sep 2018.

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