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

Sponsor

MEI Pharma, Inc. (Industry)

Overall Status

Recruiting

CT.gov ID

NCT03547115

Collaborator

(none)

100

Enrollment

Locations

Arm

Anticipated Duration (Months)

9.1

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

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

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.

Study Design

Study Type:

Interventional

Anticipated 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.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

Anticipated Primary Completion Date :

Apr 30, 2024

Anticipated Study Completion Date :

Mar 31, 2025

Arms and Interventions

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

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 Names:

ME-522

Drug: voruciclib and venetoclax

Voruciclib and Venetoclax will be administered orally

Other Names:

VENCLEXTA®

ME-522

Outcome Measures

Primary Outcome Measures

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)
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)

Secondary Outcome Measures

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
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
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)

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	City of Hope	Duarte	California	United States	91010
2	Northwestern Memorial Hospital	Chicago	Illinois	United States	60611
3	Dana Farber Cancer Institute	Boston	Massachusetts	United States	02215
4	Mayo Clinic	Rochester	Minnesota	United States	55905
5	University of Nebraska Medical Center	Omaha	Nebraska	United States	68198
6	New York University	New York	New York	United States	10016
7	Duke University	Durham	North Carolina	United States	27705
8	Oregon Health and Science University	Portland	Oregon	United States	97239
9	MD Anderson	Houston	Texas	United States	77030
10	Swedish Cancer Institute	Seattle	Washington	United States	98104
11	Froedtert Hospital & the Medical College of Wisconsin	Milwaukee	Wisconsin	United States	53226