Clinical Trials /

A Phase 1 Study of Voruciclib in Subjects With B-Cell Malignancies or AML

NCT03547115

Description:

This is a Phase 1, open-label, 3 + 3 dose escalation study to determine the safety and preliminary efficacy of voruciclib in subjects with relapsed/refractory B cell malignancies or AML after treatment with standard therapy.

Related Conditions:
  • Acute Myeloid Leukemia
  • Chronic Lymphocytic Leukemia
  • Diffuse Large B-Cell Lymphoma
  • Follicular Lymphoma
  • Mantle Cell Lymphoma
  • Marginal Zone Lymphoma
  • Small Lymphocytic Lymphoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: A Phase 1 Study of Voruciclib in Subjects With B-Cell Malignancies or AML
  • Official Title: A Phase 1, Open-label, Study of Voruciclib in Subjects With Relapsed and/or Refractory B Cell Malignancies or Acute Myeloid Leukemia After Failure of Prior Standard Therapies

Clinical Trial IDs

  • ORG STUDY ID: ME-522-001
  • NCT ID: NCT03547115

Conditions

  • Follicular Lymphoma (FL)
  • Mantle Cell Lymphoma (MCL)
  • Marginal Zone Lymphoma (MZL)
  • Small Lymphocytic Lymphoma (SLL)
  • Chronic Lymphocytic Leukemia (CLL)
  • Diffuse Large B-cell Lymphoma (DLBCL)
  • Acute Myeloid Leukemia (AML)

Interventions

DrugSynonymsArms
VoruciclibVoruciclib

Purpose

This is a Phase 1, open-label, 3 + 3 dose escalation study to determine the safety and preliminary efficacy of voruciclib in subjects with relapsed/refractory B cell malignancies or AML after treatment with standard therapy.

Detailed Description

      This is a Phase 1, open-label, 3 + 3 dose escalation study to determine the safety and
      preliminary efficacy of voruciclib in subjects with relapsed/refractory B cell malignancies
      or AML after treatment with standard therapy.

      There will be up to 5 dose level cohorts. Up to 6 subjects will be enrolled per dose cohort
      and dose escalation will be allowed after 3 subjects have completed 1 cycle with no reported
      dose limiting toxicities (DLTs) or 6 subjects completed 1 cycle with no more than 1 DLT.
      Escalation to the next higher dose level will depend on demonstrated safety and tolerability.

      Subjects may continue to receive voruciclib while there is evidence of clinical benefit and
      acceptable toxicity as judged by the investigator.
    

Trial Arms

NameTypeDescriptionInterventions
VoruciclibExperimentalOpen-label, 3 + 3 dose escalation study with 5 planned cohorts of Voruciclib which may enroll up to 6 subjects each
  • Voruciclib

Eligibility Criteria

        Inclusion Criteria:

          -  Age ≥18 years

          -  Histologically-confirmed diagnosis of Follicular lymphoma (FL), mantle cell lymphoma
             (MCL), marginal zone lymphoma (MZL), small lymphocytic lymphoma (SLL), chronic
             lymphocytic leukemia(CLL), diffuse large B-cell lymphoma (DLBCL), or AML

             a. Subjects must have disease that has relapsed or is refractory to 2 or more prior
             regimens and in need of treatment due to progressive disease

          -  Presence of measurable disease defined per the 2008 International workshop on CLL
             guidelines, or by 2014 Lugano criteria for non-Hodgkin lymphoma (does not apply for
             AML subjects)

          -  Adequate hematologic parameters unless clearly due to the disease under study

          -  Adequate renal and hepatic function, per laboratory reference range at screening

        Exclusion Criteria:

          -  For CLL subjects: only known histological transformation to an aggressive lymphoma

          -  For AML subjects:

               1. Acute promyelocytic leukemia

               2. Peripheral blast count > 25 × 10 9/L

          -  Known central nervous system involvement

          -  Significant cardiovascular disease

          -  Significant screening ECG abnormalities

          -  Subjects who require warfarin, anti-cancer therapeutics or investigational agents

          -  Evidence of an ongoing systemic bacterial, fungal, or viral infection (including upper
             respiratory tract infections) at the time of start of voruciclib therapy

          -  Receipt of an allogeneic transplant within 6 months or an autologous transplant within
             the preceding 3 months; evidence of ongoing graft-versus-host disease (GVHD)

          -  Prior therapy with a cyclin-dependent kinase (CDK9) inhibitor

          -  Ongoing immunosuppressive treatment at the time of the start of voruciclib therapy,
             including systemic or enteric corticosteroids except as follows:

               1. Prior to the start of voruciclib therapy, subjects may be using systemic
                  corticosteroids (≤20 mg/day of prednisone or equivalent), topical, or inhaled
                  corticosteroids

               2. During study therapy, subjects may use systemic, topical, or enteric
                  corticosteroids, if needed
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Determine the safety and tolerability of Voruciclib
Time Frame:2 years
Safety Issue:
Description:Safety will be measured by the incidence of all AEs and SAEs, timing, grade [CTCAE v4.03] severity, seriousness, relatedness. Tolerability will be measured by the incidence of DLTs (dose limiting toxicities)

Secondary Outcome Measures

Measure:Overall Response Rate (ORR)
Time Frame:2 years
Safety Issue:
Description:defined as the sum of complete response (CR), complete remission with incomplete marrow recovery (CRi) and partial response (PR) for B-cell malignancies, or for AML the sum of CR/CRi rate by the 2017 European LeukemiaNet (ELN) criteria
Measure:Duration of Response (DOR)
Time Frame:2 years
Safety Issue:
Description:defined as the time from the initial determination of response to the time of disease progression or death on study, which ever occurs first
Measure:Rate of CR/CRi
Time Frame:2 years
Safety Issue:
Description:defined as the proportion of subjects with CR and CRi (i.e 2 CRs or CRis at least 28 days apart) according to IWG criteria
Measure:Progression Free Survival (PFS)
Time Frame:2 years
Safety Issue:
Description:defined as the time from the first dose of study drug administration (Cycle 1 Day 1) to disease recurrence or progression as defined by IWG criteria, or death on study
Measure:Evaluate the PK of Voruciclib
Time Frame:2 years
Safety Issue:
Description:Determined by the Area Under the Concentration time curve (AUC)
Measure:Evaluate the PK of Voruciclib Cmax
Time Frame:2 years
Safety Issue:
Description:Determined by Peak Plasma Concentration (Cmax)

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:MEI Pharma, Inc.

Trial Keywords

  • B-Cell Malignancies, AML, Voruciclib, Cyclin Dependent Kinase Inhibitor

Last Updated

November 13, 2019