A Study of Voruciclib Alone or in Combination With Venetoclax in Subjects With B-Cell Malignancies or AML

August 3, 2023 updated by: MEI Pharma, Inc.

Phase 1, Open-label, Study of Voruciclib in Subjects With Relapsed and/or Refractory B Cell Malignancies or AML After Failure of Prior Standard Therapies and Voruciclib in Combination With Venetoclax in Subjects With Relapsed/Refractory AML

This is a Phase 1, open-label, dose escalation study to determine the safety and preliminary efficacy of voruciclib monotherapy in subjects with relapsed/refractory B cell malignancies or AML after failure of standard therapies or voruciclib in combination with venetoclax in subjects with relapsed or refractory AML

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

This is a Phase 1, open-label, 3 + 3 dose escalation and expansion study to determine the safety and preliminary efficacy of voruciclib monotherapy in subjects with relapsed/refractory B cell malignancies or AML after failure of prior standard therapies or voruciclib in combination with venetoclax in subjects with relapsed or refractory AML. Escalation to the next higher dose level will depend on demonstrated safety and tolerability at each dose level.

Study Type

Interventional

Enrollment (Estimated)

100

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • United States
    • California
      • Duarte, California, United States, 91010
        • Recruiting
        • City of Hope
    • Illinois
      • Chicago, Illinois, United States, 60611
        • Recruiting
        • Northwestern Memorial Hospital
    • Massachusetts
      • Boston, Massachusetts, United States, 02215
        • Active, not recruiting
        • Dana Farber Cancer Institute
    • Minnesota
      • Rochester, Minnesota, United States, 55905
        • Recruiting
        • Mayo Clinic
    • Nebraska
      • Omaha, Nebraska, United States, 68198
        • Recruiting
        • University of Nebraska Medical Center
    • New York
      • New York, New York, United States, 10016
        • Active, not recruiting
        • New York University
    • North Carolina
      • Durham, North Carolina, United States, 27705
        • Active, not recruiting
        • Duke University
    • Oregon
      • Portland, Oregon, United States, 97239
        • Recruiting
        • Oregon Health and Science University
    • Texas
      • Houston, Texas, United States, 77030
        • Recruiting
        • MD Anderson
    • Virginia
      • Charlottesville, Virginia, United States, 22903
        • Recruiting
        • University of Virginia
    • Washington
      • Seattle, Washington, United States, 98104
        • Active, not recruiting
        • Swedish Cancer Institute
    • Wisconsin
      • Milwaukee, Wisconsin, United States, 53226
        • Recruiting
        • Froedtert Hospital & the Medical College of Wisconsin

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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:

  • History of pneumonitis of any cause
  • 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
  • Prior solid organ transplantation
  • 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
  • Symptomatic/uncontrolled HIV infection/AIDS, or currently taking contraindicated medications for HIV control

  • Ongoing immunosuppressive treatment including calcineurin inhibitors at the time of the start of study treatment, including systemic or enteric corticosteroids except as follows:

    1. Prior to the start of study treatment, 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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: voruciclib monotherapy and voruciclib in combination with venetoclax

voruciclib monotherapy - Open-label, 3 + 3 dose escalation study which may enroll up to 6 subjects at each dose level and disease type (AML or B-cell malignancies)

voruciclib and venetoclax - Open-label, 3 + 3 dose escalation study which may enroll up to 6 subjects at each dose level for AML subjects
Drug: voruciclib monotherapy
Voruciclib will be administered orally
Other Names:
  • ME-522
Drug: voruciclib and venetoclax
Voruciclib and Venetoclax will be administered orally
Other Names:
  • VENCLEXTA®
  • ME-522

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Determine the safety and tolerability of voruciclib
Time Frame: 2 years

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)
2 years
Determine the safety and tolerability of voruciclib in combination with venetoclax in subjects with AML.
Time Frame: 2 years

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)
2 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall Response Rate (ORR)
Time Frame: 2 years
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
2 years
Duration of Response (DOR)
Time Frame: 2 years
defined as the time from the initial determination of response to the time of disease progression or death on study, which ever occurs first
2 years
Progression Free Survival (PFS)
Time Frame: 2 years
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
2 years
Evaluate the PK of voruciclib
Time Frame: 2 years
Determined by the Area Under the Concentration time curve (AUC)
2 years
Evaluate the PK of voruciclib Cmax in combination with venetoclax Determined by the Area Under the Concentration time curve (AUC)
Time Frame: 2 years
Determined by the Area Under the Concentration time curve (AUC)
2 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

MEI Pharma, Inc.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 31, 2018

Primary Completion (Estimated)

April 30, 2024

Study Completion (Estimated)

March 31, 2025

Study Registration Dates

First Submitted

May 24, 2018

First Submitted That Met QC Criteria

May 24, 2018

First Posted (Actual)

June 6, 2018

Study Record Updates

Last Update Posted (Actual)

August 7, 2023

Last Update Submitted That Met QC Criteria

August 3, 2023

Last Verified

August 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ME-522-001

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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