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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03547115
Recruitment Status : Recruiting
First Posted : June 6, 2018
Last Update Posted : August 12, 2022
Sponsor:
Information provided by (Responsible Party):
MEI Pharma, Inc.

Brief Summary:
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

Condition or disease Intervention/treatment Phase
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) Drug: voruciclib monotherapy Drug: voruciclib and venetoclax Phase 1

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 100 participants
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 alone or in combination with venetoclax.
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : May 31, 2018
Estimated Primary Completion Date : April 30, 2024
Estimated Study Completion Date : March 31, 2025


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 Name: ME-522

Drug: voruciclib and venetoclax
Voruciclib and Venetoclax will be administered orally
Other Names:
  • VENCLEXTA®
  • ME-522




Primary Outcome Measures :
  1. 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. 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)



Secondary Outcome Measures :
  1. 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. 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

  3. 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

  4. Evaluate the PK of voruciclib [ Time Frame: 2 years ]
    Determined by the Area Under the Concentration time curve (AUC)

  5. 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)



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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:

  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03547115


Contacts
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Contact: MEI Pharma 858-369-7100 Patients@meipharma.com

Locations
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United States, California
City of Hope Recruiting
Duarte, California, United States, 91010
United States, Illinois
Northwestern Memorial Hospital Recruiting
Chicago, Illinois, United States, 60611
United States, Massachusetts
Dana Farber Cancer Institute Recruiting
Boston, Massachusetts, United States, 02215
United States, Minnesota
Mayo Clinic Recruiting
Rochester, Minnesota, United States, 55905
United States, Nebraska
University of Nebraska Medical Center Recruiting
Omaha, Nebraska, United States, 68198
United States, New York
New York University Recruiting
New York, New York, United States, 10016
United States, North Carolina
Duke University Terminated
Durham, North Carolina, United States, 27705
United States, Oregon
Oregon Health and Science University Recruiting
Portland, Oregon, United States, 97239
United States, Texas
MD Anderson Recruiting
Houston, Texas, United States, 77030
United States, Washington
Swedish Cancer Institute Recruiting
Seattle, Washington, United States, 98104
United States, Wisconsin
Froedtert Hospital & the Medical College of Wisconsin Recruiting
Milwaukee, Wisconsin, United States, 53226
Sponsors and Collaborators
MEI Pharma, Inc.
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Responsible Party: MEI Pharma, Inc.
ClinicalTrials.gov Identifier: NCT03547115    
Other Study ID Numbers: ME-522-001
First Posted: June 6, 2018    Key Record Dates
Last Update Posted: August 12, 2022
Last Verified: August 2022

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by MEI Pharma, Inc.:
B-Cell Malignancies, AML, voruciclib, venetoclax, CDK Inhibitor
Additional relevant MeSH terms:
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Lymphoma
Leukemia
Leukemia, Myeloid, Acute
Neoplasms
Leukemia, Lymphocytic, Chronic, B-Cell
Lymphoma, Mantle-Cell
Lymphoma, Large B-Cell, Diffuse
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Leukemia, Myeloid
Lymphoma, Non-Hodgkin
Leukemia, Lymphoid
Lymphoma, B-Cell
Leukemia, B-Cell
Venetoclax
Voruciclib
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action