Clinical Trials /

Phase 1/2 Study of the ERK1/2 Inhibitor BVD-523 in Patients With Acute Myelogenous Leukemia or Myelodysplastic Syndromes

NCT02296242

Description:

This study is being performed to assess the safety, tolerability, and preliminary clinical effects of BVD-523 given orally, twice daily for 21-day cycles, in patients with Acute Myelogenous Leukemia (AML) or Myelodysplastic Syndrome (MDS).

Related Conditions:
  • Acute Myeloid Leukemia
  • Myelodysplastic Syndromes
Recruiting Status:

Completed

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Phase 1/2 Study of the ERK1/2 Inhibitor BVD-523 in Patients With Acute Myelogenous Leukemia or Myelodysplastic Syndromes
  • Official Title: Phase 1/2 Dose-Escalation, Safety, Clinical Activity, Pharmacokinetic and Pharmacodynamic Study of the ERK1/2 Inhibitor BVD-523 in Patients With Acute Myelogenous Leukemia or Myelodysplastic Syndromes

Clinical Trial IDs

  • ORG STUDY ID: BVD-523-02
  • SECONDARY ID: BVD-523-02
  • NCT ID: NCT02296242

Conditions

  • Acute Myelogenous Leukemia
  • Myelodysplastic Syndrome

Interventions

DrugSynonymsArms
BVD-523BVD-523

Purpose

This study is being performed to assess the safety, tolerability, and preliminary clinical effects of BVD-523 given orally, twice daily for 21-day cycles, in patients with Acute Myelogenous Leukemia (AML) or Myelodysplastic Syndrome (MDS).

Detailed Description

      The study is being performed to assess the safety and tolerability of BVD-523 given orally,
      twice daily for 21-day cycles.

      Part 1 of the study will establish dose limiting toxicities (DLT), maximum tolerated dose
      (MTD), and the recommended Phase 2 dose (RP2D).

      In Part 2 of the study, additional patients with particular tumor types and/or cancers
      harboring specific genetic mutations will be recruited for treatment at the Recommended Phase
      2 Dose (RP2D). Patients may also be assessed pharmacodynamic measures in healthy or malignant
      tissues, using biomarker assays for phosphorylation, cytotoxic or cytostatic measures.
    

Trial Arms

NameTypeDescriptionInterventions
BVD-523Experimental
  • BVD-523

Eligibility Criteria

        Inclusion Criteria:

          -  Have either of the following diagnoses:

               1. Morphologically confirmed acute myeloid leukemia (AML), except acute
                  promyelocytic leukemia (APL), including leukemia secondary to prior therapy or
                  antecedent hematologic disorder (e.g., MDS or myeloproliferative disorders), who
                  have failed to achieve CR or who have relapsed after prior therapy and are not
                  candidates for potentially curative therapy

               2. Intermediate-2 or High-grade risk MDS (including chronic myelomonocytic leukemia
                  (CMML))

          -  Have received at least one prior therapy. Patients who are over age 65 and have not
             received therapy for AML are also eligible, if they are not candidates for induction
             chemotherapy

          -  ECOG performance status of 0 to 2

          -  Predicted life expectancy of ≥ 3 months

          -  Adequate liver, renal and cardiac function

        For Group 1 in Part 2 of the Study ONLY:

        • Positive for RAS mutation at a Clinical Laboratory Improvement Amendments
        (CLIA)-certified laboratory prior to study entry

        Exclusion Criteria:

          -  Concomitant malignancies except carcinoma in situ, basal or squamous cell skin
             carcinoma; low grade prostate cancer treated with prostatectomy more than 10 years
             ago; early stage melanoma treated with complete surgical excision more than 5 years
             ago; carcinoma in situ of cervix treated with cone procedure more than 8 years ago

          -  Gastrointestinal condition which could impair absorption of study medication

          -  Uncontrolled or severe intercurrent medical condition

          -  Patients with rapidly increasing peripheral blood blast counts

          -  Known uncontrolled central nervous system involvement

          -  Any cancer-directed therapy within 28 days or 5 half-lives, whichever is shorter

          -  Any concurrent or prior use of an investigational drug (including MEK inhibitors)
             within previous 28 days or 5 half-lives, whichever is shorter

          -  Received chemotherapy regimens with delayed toxicity within the last four weeks (six
             weeks for prior nitrosourea or mitomycin C). Received chemotherapy regimens given
             continuously or on a weekly basis with limited potential for delayed toxicity within
             the last two weeks.

          -  Ongoing anticoagulant therapy that cannot be held if necessary to permit bone marrow
             sampling.

          -  Major surgery within 4 weeks prior to first dose

          -  Pregnant or breast-feeding women

          -  Any evidence of serious active infections

          -  Any important medical illness or abnormal laboratory finding that would increase the
             risk of participating in this study

          -  A history or current evidence/risk of retinal vein occlusion or central serous
             retinopathy

          -  Concurrent therapy with drugs known to be strong inhibitors of CYP1A2, CYP2D6, and
             CYP3A4, or strong inducers of CYP3A4
      
Maximum Eligible Age:100 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Number of Patients With Dose Limiting Toxicities
Time Frame:In the first 21 days of treatment
Safety Issue:
Description:DLT defined using CTCAE v.4.03. All toxicities were considered to be related to BVD523 if not definitively explained by underlying disease, intercurrent illness, or con meds.

Secondary Outcome Measures

Measure:Clinical Evidence of Cancer Response in Bone Marrow Biopsies
Time Frame:Until patient discontinuation; ~24 months on average
Safety Issue:
Description:Assessments were made via bone marrow biopsies using the International Working Group 2003 and 2006 criteria for AML or MDS, respectively. Bone marrow assessments (aspiration or biopsy, cytogenetics) were collected prior to therapy on Day 1 and Day 22, every 2 cycles thereafter, as well as at the final study visit if discontinuation was not due to disease progression. Some patients were unable to have bone marrow assessments taken at any or all of the time points. Shown is best response across all time points. Less than partial remission/response (<PR), partial remission/response (PR), complete remission/response with incomplete platelet recovery (CRp), or complete remission/response (CR).
Measure:Duration of Disease Control in Patients That Respond
Time Frame:Until patient discontinuation; ~24 months on average
Safety Issue:
Description:Assessments were made via bone marrow biopsies using the International Working Group 2003 and 2006 criteria for AML or MDS, respectively. Progression-free survival (PFS) and duration of response (DOR) of AML or MDS patients was assessed in patients treated with BVD-523 that achieved complete remission/response (CR) or complete remission/response with incomplete platelet recovery (CRp). <PR = less than partial remission/response. Shown is the duration (number of days) of CR or CRp response for the 2 patients in part 2 that obtained this level of response.

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Completed
Lead Sponsor:BioMed Valley Discoveries, Inc

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