Clinical Trials /

MCLA-117 in Acute Myelogenous Leukemia

NCT03038230

Description:

This is a First-in-Human, single arm, open-label, multi-national study designed to determine the safety, tolerability and preliminary efficacy of MCLA 117.

Related Conditions:
  • Acute Myeloid Leukemia
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: MCLA-117 in Acute Myelogenous Leukemia
  • Official Title: A Phase 1, Multinational Study of MCLA-117 in Acute Myelogenous Leukemia

Clinical Trial IDs

  • ORG STUDY ID: MCLA-117-CL01
  • SECONDARY ID: 2015-003704-23
  • NCT ID: NCT03038230

Conditions

  • Acute Myelogenous Leukemia
  • Acute Myeloid Leukemia

Interventions

DrugSynonymsArms
MCLA-117 bispecific antibodybispecific, human bispecific common light chain, bispecific IgG1 targeting CLEC12A and CD3MCLA-117 bispecific antibody

Purpose

This is a First-in-Human, single arm, open-label, multi-national study designed to determine the safety, tolerability and preliminary efficacy of MCLA 117.

Detailed Description

      Study Design :

      This open label, single arm, multinational, first-in-human study consists of 2 parts. Part 1
      consists of dose escalation cohorts and Part 2 is a dose expansion cohort.

      The study population will include adult AML patients (and all subtypes of AML) with relapse
      or refractory disease and newly diagnosed elderly untreated AML patients with high risk
      cytogenetics.

      In Part 1, dose escalations cohorts are followed until dose-limiting toxicity (DLT) or a
      maximum tolerated dose (MTD) or RecommendedPart2Dose (RP2D) is defined. Dose escalation
      decisions will be made by the Data Review Committee and will be primarily guided by safety
      data observed through the end of Cycle 1, as well as on-going assessment of safety beyond
      Cycle 1 in later cohorts.

      Part 2 will begin once the MTD or RP2D is determined in Part 1. Part 2 will further
      characterize the safety, tolerability, Pharmacokinetic (PK), Pharmacodynamic (PD),
      immunogenicity and to assess preliminary efficacy of MCLA-117. This part will enroll at least
      15 evaluable patients (defined as evaluable for first efficacy assessment).

      For both parts, the study consists of 3 periods: a Screening period (up to 28 days prior to
      the first dose of study drug); a Treatment period (first dose of study drug until the last
      dose of study drug with treatment cycles of 28 days); and a Follow Up period (through 30 days
      after the last dose and quarterly checks for survival data for up to 1 year). Participants'
      safety will be monitored throughout the study. Patients will be permitted to receive MCLA-117
      beyond Cycle 1 if conditions allow this.

      Number of Sites:

      Approximately 8 centers in five countries are estimated to be involved during Parts 1 and 2
      of the study. Additional sites may be added to ensure there is an acceptable enrollment rate
      or to replace non-enrolling/withdrawn sites.
    

Trial Arms

NameTypeDescriptionInterventions
MCLA-117 bispecific antibodyExperimentalDose escalation cohorts, with escalating doses of MCLA-117 until MTD or RP2D is reached. The dose is given weekly after initial ramp-up dosing steps. Each Cycle is 28 days. Single agent treatment. Part 2-Expansion Cohort: The RP2D of MCLA-117 is given weekly after initial ramp-up dosing steps. Each Cycle is 28 days. Single agent treatment.
  • MCLA-117 bispecific antibody

Eligibility Criteria

        Inclusion Criteria:

          1. Male or female age ≥18 years old;

          2. Signed informed consent form

          3. AML either de novo or secondary [any subtype except acute promyelocytic leukemia
             (APL)] who either:

               1. are in relapse to standard therapy following an initial response

               2. failed primary induction therapy with no CR (failed ≥2 induction attempts) and
                  for whom no other approved therapy is available

               3. newly diagnosed untreated AML in patients ≥ 65 years of age with high risk
                  cytogenetics, if they are not candidates for standard available induction
                  chemotherapy

          4. Must have baseline BM sample taken by BMA/BMB within 21 days prior to first dose of
             MCLA-117 for CLEC12A detection;

          5. Estimated life expectancy of at least 8 weeks;

          6. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2;

          7. Significant toxicities incurred as a result of previous anti-cancer therapy resolved
             to ≤ Grade 1 (NCI-CTCAE version 4.03);

          8. Acceptable laboratory values at screening;

          9. Male patients must agree to use an adequate and medically accepted method of
             contraception throughout the study and for at least 6 months after if their sexual
             partners are women of child bearing potential (WOCBP).

         10. WOCBP must be using highly effective and medically accepted method of contraception to
             avoid pregnancy throughout the study and for at least 6 months after the study ;

         11. WOCBP must have a negative serum or urine pregnancy test within 72 hours prior to the
             start of study drug.

         12. Peripheral blast count </= 30,000/mm3 at the time of initiation of infusion on Cycle 1
             Day 1.

        Exclusion Criteria:

          1. Diagnosis of chronic myelogenous leukemia in blast crisis;

          2. Prior hematopoietic stem cell transplantation;

          3. Cancer chemotherapy within four weeks prior to start of MCLA-117;

          4. Previous treatment with radiotherapy, or immunotherapeutic agents, or receipt of live
             vaccines in the 4 weeks prior to study drug administration;

          5. Previous treatment with any other investigational agents within 4 weeks prior to
             MCLA-117 administration;

          6. Concurrent need of use of corticosteroids > 10 mg/day of oral prednisone or the
             equivalent, except topical preparations (e.g., topical creams, steroid inhaler, nasal
             spray or ophthalmic solution);

          7. Use of immunosuppressant medications within 4 weeks of MCLA-117 administration;

          8. Clinically active central nervous system (CNS) leukemia;

          9. Patients who are pregnant or lactating;

         10. Patients with an active infection or with an unexplained fever during screening or on
             the first scheduled day of dosing;

         11. Patients with known hypersensitivity to any of the components of MCLA-117 or who have
             had prior hypersensitivity reactions to human or humanized monoclonal antibodies;

         12. Patients with known HIV, hepatitis B or C;

         13. Patients with New York Heart Association Class III or IV congestive heart failure or
             left ventricular ejection fraction (LVEF) < 50%, or significant uncontrolled cardiac
             disease, current diagnosis of unstable angina, uncontrolled congestive heart failure,
             new myocardial infarction, or ventricular arrhythmia requiring medication;

         14. Prior malignancy (other than basal cell carcinoma and cervical in situ carcinoma)
             unless treated with a curative intend and without evidence of malignant disease for 1
             year before screening. Patients with prior hematologic malignancies that have
             progressed to AML (such as Myelodysplastic syndrome, myeloproliferative neoplasms,
             bi-phenotypic leukemias, AcuteLymphocyticLeukemia) or AML that has relapsed are
             eligible;

         15. Urinary protein >2+ possibly indicative of renal disease. If the 24 hours urine
             protein shows a result of < 100 mg protein, subject can be eligible;

         16. Patients with any other medical or psychological condition deemed by the Investigator
             to be likely to interfere with a patient's ability to sign informed consent, cooperate
             and participate in the study, or interfere with the interpretation of the results;

         17. WOCBP or males with a WOCB partners not willing to use highly effective and medically
             accepted methods of contraception for 6 months after last study drug administration.

         18. Need for concurrent other cytoreductive chemotherapy.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Number of participants with Dose Limiting Toxicities (DLT)
Time Frame:28 days
Safety Issue:
Description:Evaluation of number of participants with treatment related toxicity observed during a dose escalation step for 1 Cycle

Secondary Outcome Measures

Measure:Maximum plasma concentration [Cmax]
Time Frame:Day 22 predose, 5 minutes prior to End of Infusion (EOI), 1h, 2h, 4h, 8h, 24h, 72h, 6 days after EOI
Safety Issue:
Description:Maximum plasma concentration [Cmax] as measured from all individual plasma concentrations
Measure:Clearance of plasma
Time Frame:Day 22 predose, 5 minutes prior to End of Infusion (EOI), 1h, 2h, 4h, 8h, 24h, 72h, 6 days after EOI
Safety Issue:
Description:Clearance of plasma
Measure:Volume of distribution at steady state [Vss]
Time Frame:Day 22 predose, 5 minutes prior to End of Infusion (EOI), 1h, 2h, 4h, 8h, 24h, 72h, 6 days after EOI
Safety Issue:
Description:Volume of distribution at steady state [Vss]
Measure:Time to reach maximum plasma concentration [Tmax]
Time Frame:Day 22 predose, 5 minutes prior to End of Infusion (EOI), 1h, 2h, 4h, 8h, 24h, 72h, 6 days after EOI
Safety Issue:
Description:Time to reach maximum plasma concentration [Tmax]
Measure:Half-life [t1/2]
Time Frame:Day 22 predose, 5 minutes prior to End of Infusion (EOI), 1h, 2h, 4h, 8h, 24h, 72h, 6 days after EOI
Safety Issue:
Description:Half-life [t1/2] calculated as time from all individual plasma concentrations to reach 50% of maximum concentration
Measure:Area under the concentration versus time curve from time zero to time t [AUC0-t]
Time Frame:1 week
Safety Issue:
Description:Area under the concentration versus time curve [AUC0-t]
Measure:Incidence of AntiDrugAntibodies (ADA) against MCLA-117
Time Frame:24 months
Safety Issue:
Description:Number of participants with ADAs against MCLA-117 as measured in serum
Measure:Serum titer of ADAs against MCLA-117
Time Frame:Day 1 of each cycle
Safety Issue:
Description:Serum titer of ADAs against MCLA-117 as measured in serum
Measure:Serum titer of ADAs against MCLA-117
Time Frame:Day 28 of each cycle
Safety Issue:
Description:Serum titer of ADAs against MCLA-117 as measured in serum
Measure:Cytokine levels
Time Frame:Cycle 1: Day 1, 4, 8 and 28 at predose, 4h and 24h after end of infusion
Safety Issue:
Description:Change in profile of cytokine upon administration of MCLA-117 compared to baseline
Measure:Number of myeloblasts
Time Frame:Day 1 of every cycle and through study completion, an average of 2 months
Safety Issue:
Description:number of blasts in peripheral blood and in bone marrow
Measure:Objective response
Time Frame:Day 1 of every cycle and through study completion, an average of 2 months
Safety Issue:
Description:Objective response is assessed by Cheson 2003

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Merus N.V.

Trial Keywords

  • human bispecific full length IgG antibody, CLEC12A, CD3
  • MCLA-117
  • First in Human
  • Antibodies, Bispecific
  • Immunologic Factors
  • relapsed, refractory patient
  • AML, minimal residual disease (MRD)
  • Acute Myelogenous Leukemia
  • Acute Myeloid Leukemia
  • CD34+CD38
  • T-cell recruiting

Last Updated

August 10, 2018