Clinical Trials /

A Study of MBG453 in Combination With Azacitidine and Venetoclax in AML Patients Unfit for Chemotherapy

NCT04150029

Description:

This trial will seek to extend the preliminary findings of efficacy of MBG453 in combination with hypomethylating agents (HMA) by evaluating MBG453 in combination with the HMA azacitidine and the Bcl-2 inhibitor venetoclax. The primary purpose of Part 1 (Safety Run-in) is to rule out excessive toxicity of MBG453, when administered in combination with azacitidine and venetoclax. The primary purpose of the combined Part 1 and Part 2 (Safety run-in and Expansion Part) is to evaluate efficacy of MBG453, when administered in combination with azacitidine and venetoclax in adult patients with newly diagnosed AML, who are not suitable for treatment with intensive chemotherapy.

Related Conditions:
  • Acute Myeloid Leukemia
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: A Study of MBG453 in Combination With Azacitidine and Venetoclax in AML Patients Unfit for Chemotherapy
  • Official Title: A Phase II Multi-center, Single Arm, Safety and Efficacy Study of MBG453 in Combination With Azacitidine and Venetoclax for the Treatment of Acute Myeloid Leukemia (AML) in Adult Patients Unfit for Chemotherapy

Clinical Trial IDs

  • ORG STUDY ID: CMBG453C12201
  • SECONDARY ID: 2019-000439-14
  • NCT ID: NCT04150029

Conditions

  • Acute Myeloid Leukemia

Interventions

DrugSynonymsArms
MBG453MBG453+Venetoclax +Azacitidine
VenetoclaxMBG453+Venetoclax +Azacitidine
AzacitidineMBG453+Venetoclax +Azacitidine

Purpose

This trial will seek to extend the preliminary findings of efficacy of MBG453 in combination with hypomethylating agents (HMA) by evaluating MBG453 in combination with the HMA azacitidine and the Bcl-2 inhibitor venetoclax. The primary purpose of Part 1 (Safety Run-in) is to rule out excessive toxicity of MBG453, when administered in combination with azacitidine and venetoclax. The primary purpose of the combined Part 1 and Part 2 (Safety run-in and Expansion Part) is to evaluate efficacy of MBG453, when administered in combination with azacitidine and venetoclax in adult patients with newly diagnosed AML, who are not suitable for treatment with intensive chemotherapy.

Trial Arms

NameTypeDescriptionInterventions
MBG453+Venetoclax +AzacitidineExperimentalPatients will receive MBG453 in combination with Venetoclax and Azacitidine
  • MBG453
  • Venetoclax
  • Azacitidine

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. Newly diagnosed with AML based on 2016 WHO classification (Arber et al 2016) and not
             suitable for intensive chemotherapy defined as: age ≥75, ECOG performance Status 2 or
             3, or any of the following comomorbitities: severe cardiac comorbities (including
             congestive heart failure, LVEF ≤ 50%, chronic stable Angina) , pulmonary comorbidity
             (DLCO ≤ 65% or FEVI ≤ 65%). moderate hepatic impairment (with total Bilirubin >1.5 to
             3x ULN) , renal impairment (eGFR≥ 30 ml/min/1.73m^2 to 45 30 ml/min/1.73m^2), or other
             comorbidity incompatible with intensive chemotherapy per Investigator assessement and
             approved by the Novartis Medical monitor)

          4. .Not planned for hematopoietic stem-cell transplantation (HSCT)

          5. .Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 , 2 or 3

        Exclusion Criteria:

          1. Prior exposure to TIM-3 directed therapy

          2. Subjects with therapy related AML.

          3. History of severe hypersensitivity reactions to any ingredient of study drug(s)
             (azacitidine, venetoclax 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. Previous treatment at any time, with any of the following antineoplastic agents,
             approved or investigational; checkpoint inhibitors, venetoclax and hypomethylating
             agents (HMAs) such as decitabine or azacitidine.

          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:Incidence of dose limiting toxicities (Safety run-in patients only)
Time Frame:From Cycle 1 Day 8 to end of Cycle 2; Cycle =28 Days
Safety Issue:
Description:Assessment of tolerability of MBG in combination with venetoclax and azacitidine

Secondary Outcome Measures

Measure:Percentage of subjects achieving a complete remission (CR) or complete remission with incomplete hematologic blood count recovery (CRi)
Time Frame:every 12 weeks (starting at week 5) for up to 48 months from last patient first treatment
Safety Issue:
Description:Assessing the durability of complete remission (CR) or complete remission with incomplete hematologic blood count recovery (CRi) rate by determining the relapse free survival (RFS) in participants who achieve complete response (CR)
Measure:Time from date of first documented CR or CRi to the date of first documented relapse or death due to any cause
Time Frame:every 12 weeks (starting at week 5) for up to 48 months from last patient first treatment
Safety Issue:
Description:Time to relapse from CR/CRi or death (relapse free survival), whichever occurs first
Measure:Time from the date of the first documented CR to the date of first documented relapse or death due to any cause
Time Frame:every 12 weeks (starting at week 5) for up to 48 months from last patient first treatment
Safety Issue:
Description:Assessing the durability of complete remission (CR) by determining the Relapse Free Survival (RFS) in subjects who achieved CR, whichever occurs first
Measure:Time from start of treatment until death, relapse from CR, or treatment failure, whichever occurs first
Time Frame:every 12 weeks (starting at week 5) for up to 48 months from last patient first treatment
Safety Issue:
Description:Assessing event free survival (EFS).
Measure:Time from start of treatment to death due to any cause (overall survival)
Time Frame:date of start of treatment to date of death due to any reason (for up to 48 months from last patient first treatment)
Safety Issue:
Description:Time to death due to any cause to assess overall survival
Measure:Peak Serum Concentration (Cmax) MBG453
Time Frame:Cycle 1 Day 8 (end of infusion) and Cycle 3 Day 8 (end of infusion), cycle = 28 days
Safety Issue:
Description:Maximal concentration of MBG453
Measure:Trough Serum Concentration (Cmin) MBG453
Time Frame:Day 8 of Cycle 1,2,3,6,9,12,18, 24 and through treatment completion, an average of 24 months
Safety Issue:
Description:Concentration of MBG453 prior to next dosing or after end of treatment
Measure:Trough Plasma Concentration (Cmin) Venetoclax
Time Frame:Day 8 of Cycle 1, 3 and 8 ; Cycle =28 days
Safety Issue:
Description:Trough concentration of venetoclax on treatment
Measure:Anti-drug Antibody (ADA) prevalence at baseline
Time Frame:prior to first dose of MGB453 on Cycle 1 Day 8 (cycle =28 Days)
Safety Issue:
Description:Immunogenicity to MBG453 prior to MBG453 exposure
Measure:ADA prevalence on-treatment
Time Frame:Throughout study until 150 day safety follow-up
Safety Issue:
Description:Immunogenicity to MBG453 on Treatment and after treatment
Measure:Percentage of MRD-negative subjects in the full study population and in subjects achieving CR or CRi
Time Frame:every 12 weeks (starting at week 5) for up to 48 months from last patient first treatment
Safety Issue:
Description:Rate of MRD-negative subjects
Measure:Rate of subjects who achieve transfusion independence from baseline and while on treatment.
Time Frame:from start of treatment up to 48 months from last patient first treatment
Safety Issue:
Description:Percentage of subjects who are not dependent on blood transfusions for more than 8 weeks will be determined and related to the total number of patients participating to report percentage

Details

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

Trial Keywords

  • MBG453
  • Venetoclax
  • Azacitidine
  • Phase 2
  • AML
  • Acute myeloid Leukemia

Last Updated

June 21, 2020