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

Acute Myeloid Leukemia (AML) Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03547115
• Other study ID #: ME-522-001
• Status: Recruiting
• Phase: Phase 1
• Start date: May 31, 2018
• Est. completion date: March 31, 2025

Study information

• Verified date: August 2023
• Source: MEI Pharma, Inc.
• Contact: MEI Pharma
• Phone: 858-369-7100
• Email: Patients[@]meipharma.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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 information / eligibility

• Status: Recruiting
• Enrollment: 100
• Est. completion date: March 31, 2025
• Est. primary completion date: April 30, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Acute Myeloid Leukemia (AML)
• Chronic Lymphocytic Leukemia (CLL)
• Diffuse Large B-cell Lymphoma (DLBCL)
• Follicular Lymphoma (FL)
• Leukemia
• Leukemia, Lymphocytic, Chronic, B-Cell
• Leukemia, Myeloid, Acute
• Lymphoma
• Lymphoma, Large B-Cell, Diffuse
• Lymphoma, Mantle-Cell
• Mantle Cell Lymphoma (MCL)
• Marginal Zone Lymphoma (MZL)
• Neoplasms
• Small Lymphocytic Lymphoma (SLL)

Intervention

Drug:
• voruciclib monotherapy
Voruciclib will be administered orally
• voruciclib and venetoclax
Voruciclib and Venetoclax will be administered orally

Locations

Country	Name	City	State
United States	Dana Farber Cancer Institute	Boston	Massachusetts
United States	University of Virginia	Charlottesville	Virginia
United States	Northwestern Memorial Hospital	Chicago	Illinois
United States	City of Hope	Duarte	California
United States	Duke University	Durham	North Carolina
United States	MD Anderson	Houston	Texas
United States	Froedtert Hospital & the Medical College of Wisconsin	Milwaukee	Wisconsin
United States	New York University	New York	New York
United States	University of Nebraska Medical Center	Omaha	Nebraska
United States	Oregon Health and Science University	Portland	Oregon
United States	Mayo Clinic	Rochester	Minnesota
United States	Swedish Cancer Institute	Seattle	Washington

Sponsors (1)

Lead Sponsor	Collaborator
MEI Pharma, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)	2 years
Primary	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)	2 years
Secondary	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	2 years
Secondary	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	2 years
Secondary	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	2 years
Secondary	Evaluate the PK of voruciclib	Determined by the Area Under the Concentration time curve (AUC)	2 years
Secondary	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)	2 years