Clinical Trials /

A Study of MBG453 in Combination With Hypomethylating Agents in Subjects With IPSS-R Intermediate, High or Very High Risk Myelodysplastic Syndrome (MDS).

NCT03946670

Description:

This Phase II is a multicenter, randomized, two-arm parallel-group, double-blind, placebo-controlled study of MBG453 or placebo added to hypomethylating agents (azacitidine or decitabine) in adult subjects with IPSS-R intermediate, high or very high risk myelodysplastic syndrome (MDS) not eligible for Hematopoietic Stem Cell Transplant (HSCT) or intensive chemotherapy.

Related Conditions:
  • Myelodysplastic Syndromes
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: A Study of MBG453 in Combination With Hypomethylating Agents in Subjects With IPSS-R Intermediate, High or Very High Risk Myelodysplastic Syndrome (MDS).
  • Official Title: A Randomized, Double-blind, Placebo-controlled Phase II Multi-center Study of Intravenous MBG453 Added to Hypomethylating Agents in Adult Subjects With Intermediate, High or Very High Risk Myelodysplastic Syndrome (MDS) as Per IPSS-R Criteria

Clinical Trial IDs

  • ORG STUDY ID: CMBG453B12201
  • SECONDARY ID: 2018-004479-11
  • NCT ID: NCT03946670

Conditions

  • Myelodysplastic Syndromes

Interventions

DrugSynonymsArms
MBG453MBG453 + hypomethylating agents
PlaceboPlacebo + hypomethylating agents
Hypomethylating agentsMBG453 + hypomethylating agents

Purpose

This Phase II is a multicenter, randomized, two-arm parallel-group, double-blind, placebo-controlled study of MBG453 or placebo added to hypomethylating agents (azacitidine or decitabine) in adult subjects with IPSS-R intermediate, high or very high risk myelodysplastic syndrome (MDS) not eligible for Hematopoietic Stem Cell Transplant (HSCT) or intensive chemotherapy.

Trial Arms

NameTypeDescriptionInterventions
MBG453 + hypomethylating agentsExperimentalPatients will take MBG453 plus hypomethylating agents
  • MBG453
  • Hypomethylating agents
Placebo + hypomethylating agentsPlacebo ComparatorPatients will take placebo plus hypomethylating agents
  • Placebo
  • Hypomethylating agents

Eligibility Criteria

        Inclusion Criteria:

          1. Signed informed consent must be obtained prior to participation in the study.

          2. Age ≥ 18 years at the date of signing the informed consent form (ICF)

          3. Morphologically confirmed diagnosis of a myelodysplastic syndrome (MDS) based on 2016
             WHO classification (Arber et al 2016) by investigator assessment with one of the
             following Prognostic Risk Categories, based on the International Prognostic Scoring
             System (IPSS-R):

               -  Very high

               -  High

               -  Intermediate with at least ≥ 5% bone marrow blast

          4. Not eligible for intensive chemotherapy

          5. Not eligible for hematopoietic stem-cell transplantation (HSCT)

          6. Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2

        Exclusion Criteria:

          1. Prior exposure to TIM-3 directed therapy at any time. Prior therapy with immune check
             point inhibitors (e.g. anti-CTLA4, anti-PD-1, anti-PD-L1, or anti-PD-L2), cancer
             vaccines are allowed only if the last dose of the drug was administered more than 4
             months prior to randomization.

          2. Previous treatment for higher risk MDS with chemotherapy or other antineoplastic
             agents including lenalidomide and hypomethylating agent (HMAs) such as decitabine or
             azacitidine. However, previous treatment is permitted with hydroxyurea or
             leukopheresis.

          3. History of severe hypersensitivity reactions to any ingredient of study drug(s)
             (azacitidine, decitabine or MGB453) or monoclonal antibodies (mAbs) and/or their
             excipients.

          4. Current use or use within 14 days prior to randomization of systemic, steroid therapy
             (> 10 mg/day prednisone or equivalent) or any immunosuppressive therapy. Topical,
             inhaled, nasal, ophthalmic steroids are allowed. Replacement therapy, steroids given
             in the context of a transfusion are allowed and not considered a form of systemic
             treatment.

          5. Investigational treatment for MDS received within 4 weeks prior to randomization. In
             case of a checkpoint inhibitor: 4 months minimum prior to randomization interval is
             necessary to allow enrollment.

          6. Active autoimmune disease requiring systemic therapy (e.g.corticosteroids).

          7. Live vaccine administered within 30 Days prior to randomization.

        Other protocol-defined Inclusion/Exclusion may apply.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Complete remission (CR) rate
Time Frame:7 months after last patient first visit (LPFV)
Safety Issue:
Description:Modified response criteria According to International Working Group (IWG) for Myelodysplastic syndromes (MDS) as per investigator assessment.

Secondary Outcome Measures

Measure:Overall Suvival
Time Frame:Up to 4 years after last patient randomized
Safety Issue:
Description:Time from randomization to death due to any cause
Measure:Leukemia-free survival
Time Frame:Up to 4 yrs after Last Patient First Visit (LPFV)
Safety Issue:
Description:Time from randomization to ≥ 20% blasts in bone marrow/ peripheral blood (per WHO 2016 classification) or death due to any cause
Measure:Response Rate (CR/mCR/PR)
Time Frame:7 months after Last Patient First Visit (LPFV)
Safety Issue:
Description:Percentage of complete remission(CR)/marrow Complete Remission (mCR)/partial remission (PR) according to IWG-MDS as per investigator assessment
Measure:Duration of complete remission
Time Frame:Up to 4 yrs after Last Patient First Visit (LPFV)
Safety Issue:
Description:Time from the date of the first documented CR to the date of first documented relapse from CR or death due to any cause, whichever occurs first
Measure:Time to complete remission
Time Frame:7 months after Last Patient First Visit (LPFV)
Safety Issue:
Description:Time from randomization to the first documented CR
Measure:Number of subjects who are RBC/platelets transfusion independent after randomization as per IWG-MDS
Time Frame:Up to 4 years after last randomized patient
Safety Issue:
Description:Improvement in RBC/platelets transfusion independence
Measure:Percent of subjects who are red blood cells (RBC)/platelets transfusion independent after randomization as per IWG-MDS
Time Frame:Up to 4 years after last randomized patient
Safety Issue:
Description:Improvement in RBC/platelets transfusion independence
Measure:Serum concentrations for MBG453
Time Frame:At Day 8 of each cycle (1 cycle = 28 days) until cycle 6 and at day 8 of cycles 9, 12, 18 and 24, and up to 150 day of the safety follow up period
Safety Issue:
Description:Pharmacokinetics of MBG453 when given in combination with hypomethylating agents (HMA)
Measure:Immunogenicity of MBG453 when given in combination of hypomethylating agents
Time Frame:Up to 4 years after Last Patient First Visit (LPFV)
Safety Issue:
Description:Anti-drug Antibody (ADA) prevalence at baseline and ADA incidence on-treatment

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Novartis Pharmaceuticals

Trial Keywords

  • Phase II,
  • MBG453
  • TIM-3
  • decitabine
  • azacitidine
  • myelodysplastic syndrome (MDS)

Last Updated

January 2, 2020