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

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ClinicalTrials.gov Identifier: NCT03547115
Recruitment Status : Recruiting
First Posted : June 6, 2018
Last Update Posted : November 6, 2020
Sponsor:
Information provided by (Responsible Party):
MEI Pharma, Inc.

Tracking Information
First Submitted Date  ICMJE May 24, 2018
First Posted Date  ICMJE June 6, 2018
Last Update Posted Date November 6, 2020
Actual Study Start Date  ICMJE May 31, 2018
Estimated Primary Completion Date April 30, 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 5, 2018)
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)
Original Primary Outcome Measures  ICMJE
 (submitted: May 24, 2018)
Determine the safety and tolerability of voruciclib [ Time Frame: 2 years ]
measured by the number of participants with treatment related adverse events including DLTs
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: March 5, 2019)
  • 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
  • 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
  • Rate of CR/CRi [ Time Frame: 2 years ]
    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
  • 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
  • Evaluate the PK of voruciclib [ Time Frame: 2 years ]
    Determined by the Area Under the Concentration time curve (AUC)
  • Evaluate the PK of voruciclib Cmax [ Time Frame: 2 years ]
    Determined by Peak Plasma Concentration (Cmax)
Original Secondary Outcome Measures  ICMJE
 (submitted: May 24, 2018)
  • 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)
  • 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
  • Rate of CR/CRi [ Time Frame: 2 years ]
    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
  • Progression Free Survival (PFS) [ Time Frame: 2 years ]
    defined as the time from the first day of study drug administration (Cycle 1 Day 1) to disease recurrence or progression as defined by IWG criteria, or death on study
  • Evaluate the PK of voruciclib [ Time Frame: 2 years ]
    Determined by the Area Under the Concentration time curve (AUC)
  • Evaluate the PK of voruciclib Cmax [ Time Frame: 2 years ]
    Determined by Peak Plasma Concentration (Cmax)
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Phase 1 Study of Voruciclib in Subjects With B-Cell Malignancies or AML
Official Title  ICMJE 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
Brief Summary 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 and 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 and AML after treatment with standard therapy. Escalation to the next higher dose level will depend on demonstrated safety and tolerability at each dose level.

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

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description:
This is a Phase 1, open-label, 3 + 3 dose escalation study to determine the safety and preliminary efficacy of voruciclib.
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • 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)
Intervention  ICMJE Drug: voruciclib
Voruciclib is provided as 50 mg and 100 mg capsules and is administered orally once a day
Study Arms  ICMJE Experimental: voruciclib
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)
Intervention: Drug: voruciclib
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: June 10, 2020)
92
Original Estimated Enrollment  ICMJE
 (submitted: May 24, 2018)
63
Estimated Study Completion Date  ICMJE December 31, 2022
Estimated Primary Completion Date April 30, 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
  • 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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: MEI Pharma 858-369-7100 Patients@meipharma.com
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03547115
Other Study ID Numbers  ICMJE ME-522-001
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party MEI Pharma, Inc.
Study Sponsor  ICMJE MEI Pharma, Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account MEI Pharma, Inc.
Verification Date October 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP