Back to resultsA Study of Voruciclib Alone or in Combination With Venetoclax in Subjects With B-Cell Malignancies or AML
Primary Purpose
Follicular Lymphoma (FL), Mantle Cell Lymphoma (MCL), Marginal Zone Lymphoma (MZL)
Status
Recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
voruciclib monotherapy
voruciclib and venetoclax
Sponsored by
About this trial
This is an interventional treatment trial for Follicular Lymphoma (FL) focused on measuring B-Cell Malignancies, AML, voruciclib, venetoclax, CDK Inhibitor
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:
- History of pneumonitis of any cause
- For CLL subjects: only known histological transformation to an aggressive lymphoma
For AML subjects:
- Acute promyelocytic leukemia
- 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:
- Prior to the start of study treatment, subjects may be using systemic corticosteroids (≤20 mg/day of prednisone or equivalent), topical, or inhaled corticosteroids
- During study therapy, subjects may use systemic, topical, or enteric corticosteroids, if needed
Sites / Locations
- City of HopeRecruiting
- Northwestern Memorial HospitalRecruiting
- Dana Farber Cancer Institute
- Mayo ClinicRecruiting
- University of Nebraska Medical CenterRecruiting
- New York University
- Duke University
- Oregon Health and Science UniversityRecruiting
- MD AndersonRecruiting
- University of VirginiaRecruiting
- Swedish Cancer Institute
- Froedtert Hospital & the Medical College of WisconsinRecruiting
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
voruciclib monotherapy and voruciclib in combination with venetoclax
Arm Description
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
Outcomes
Primary Outcome Measures
Determine the safety and tolerability of voruciclib
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)
Determine the safety and tolerability of voruciclib in combination with venetoclax in subjects with AML.
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
Overall Response Rate (ORR)
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)
defined as the time from the initial determination of response to the time of disease progression or death on study, which ever occurs first
Progression Free Survival (PFS)
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
Determined by the Area Under the Concentration time curve (AUC)
Evaluate the PK of voruciclib Cmax in combination with venetoclax Determined by the Area Under the Concentration time curve (AUC)
Determined by the Area Under the Concentration time curve (AUC)
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03547115
Brief Title
A Study of Voruciclib Alone or in Combination With Venetoclax in Subjects With B-Cell Malignancies or AML
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
Study Type
Interventional
2. Study Status
Record Verification Date
August 2023
Overall Recruitment Status
Recruiting
Study Start Date
May 31, 2018 (Actual)
Primary Completion Date
April 30, 2024 (Anticipated)
Study Completion Date
March 31, 2025 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
MEI Pharma, Inc.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
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
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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)
Keywords
B-Cell Malignancies, AML, voruciclib, venetoclax, CDK Inhibitor
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
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)
Allocation
N/A
Enrollment
100 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
voruciclib monotherapy and voruciclib in combination with venetoclax
Arm Type
Experimental
Arm Description
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
Intervention Type
Drug
Intervention Name(s)
voruciclib monotherapy
Other Intervention Name(s)
ME-522
Intervention Description
Voruciclib will be administered orally
Intervention Type
Drug
Intervention Name(s)
voruciclib and venetoclax
Other Intervention Name(s)
VENCLEXTA®, ME-522
Intervention Description
Voruciclib and Venetoclax will be administered orally
Primary Outcome Measure Information:
Title
Determine the safety and tolerability of voruciclib
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)
Time Frame
2 years
Title
Determine the safety and tolerability of voruciclib in combination with venetoclax in subjects with AML.
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)
Time Frame
2 years
Secondary Outcome Measure Information:
Title
Overall Response Rate (ORR)
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
Time Frame
2 years
Title
Duration of Response (DOR)
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
Time Frame
2 years
Title
Progression Free Survival (PFS)
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
Time Frame
2 years
Title
Evaluate the PK of voruciclib
Description
Determined by the Area Under the Concentration time curve (AUC)
Time Frame
2 years
Title
Evaluate the PK of voruciclib Cmax in combination with venetoclax Determined by the Area Under the Concentration time curve (AUC)
Description
Determined by the Area Under the Concentration time curve (AUC)
Time Frame
2 years
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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:
History of pneumonitis of any cause
For CLL subjects: only known histological transformation to an aggressive lymphoma
For AML subjects:
Acute promyelocytic leukemia
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:
Prior to the start of study treatment, subjects may be using systemic corticosteroids (≤20 mg/day of prednisone or equivalent), topical, or inhaled corticosteroids
During study therapy, subjects may use systemic, topical, or enteric corticosteroids, if needed
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
MEI Pharma
Phone
858-369-7100
Email
Patients@meipharma.com
Facility Information:
Facility Name
City of Hope
City
Duarte
State/Province
California
ZIP/Postal Code
91010
Country
United States
Individual Site Status
Recruiting
Facility Name
Northwestern Memorial Hospital
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60611
Country
United States
Individual Site Status
Recruiting
Facility Name
Dana Farber Cancer Institute
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
Individual Site Status
Active, not recruiting
Facility Name
Mayo Clinic
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States
Individual Site Status
Recruiting
Facility Name
University of Nebraska Medical Center
City
Omaha
State/Province
Nebraska
ZIP/Postal Code
68198
Country
United States
Individual Site Status
Recruiting
Facility Name
New York University
City
New York
State/Province
New York
ZIP/Postal Code
10016
Country
United States
Individual Site Status
Active, not recruiting
Facility Name
Duke University
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27705
Country
United States
Individual Site Status
Active, not recruiting
Facility Name
Oregon Health and Science University
City
Portland
State/Province
Oregon
ZIP/Postal Code
97239
Country
United States
Individual Site Status
Recruiting
Facility Name
MD Anderson
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Individual Site Status
Recruiting
Facility Name
University of Virginia
City
Charlottesville
State/Province
Virginia
ZIP/Postal Code
22903
Country
United States
Individual Site Status
Recruiting
Facility Name
Swedish Cancer Institute
City
Seattle
State/Province
Washington
ZIP/Postal Code
98104
Country
United States
Individual Site Status
Active, not recruiting
Facility Name
Froedtert Hospital & the Medical College of Wisconsin
City
Milwaukee
State/Province
Wisconsin
ZIP/Postal Code
53226
Country
United States
Individual Site Status
Recruiting
12. IPD Sharing Statement
Learn more about this trial
A Study of Voruciclib Alone or in Combination With Venetoclax in Subjects With B-Cell Malignancies or AML
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