A Study of Voruciclib Alone or in Combination With Venetoclax in Subjects With B-Cell Malignancies or AML
- Conditions
- Diffuse Large B-cell Lymphoma (DLBCL)Chronic Lymphocytic Leukemia (CLL)Acute Myeloid Leukemia (AML)Marginal Zone Lymphoma (MZL)Follicular Lymphoma (FL)Mantle Cell Lymphoma (MCL)Small Lymphocytic Lymphoma (SLL)
- Interventions
- Registration Number
- NCT03547115
- Lead Sponsor
- 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
- 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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 100
-
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
-
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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description voruciclib monotherapy and voruciclib in combination with venetoclax voruciclib monotherapy 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 voruciclib monotherapy and voruciclib in combination with venetoclax voruciclib and 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
- Primary Outcome Measures
Name Time Method Determine the safety and tolerability of voruciclib in combination with venetoclax in subjects with AML. 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)Determine the safety and tolerability of voruciclib 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
Name Time Method Evaluate the PK of voruciclib 2 years 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) 2 years Determined by the Area Under the Concentration time curve (AUC)
Progression Free Survival (PFS) 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
Overall Response Rate (ORR) 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) 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
Trial Locations
- Locations (12)
MD Anderson
🇺🇸Houston, Texas, United States
Swedish Cancer Institute
🇺🇸Seattle, Washington, United States
Northwestern Memorial Hospital
🇺🇸Chicago, Illinois, United States
Mayo Clinic
🇺🇸Rochester, Minnesota, United States
Duke University
🇺🇸Durham, North Carolina, United States
University of Virginia
🇺🇸Charlottesville, Virginia, United States
University of Nebraska Medical Center
🇺🇸Omaha, Nebraska, United States
Dana Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
City of Hope
🇺🇸Duarte, California, United States
New York University
🇺🇸New York, New York, United States
Oregon Health and Science University
🇺🇸Portland, Oregon, United States
Froedtert Hospital & the Medical College of Wisconsin
🇺🇸Milwaukee, Wisconsin, United States