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

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

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

Study Overview

• Status: Terminated
• Conditions: Chronic Lymphocytic Leukemia (CLL); Small Lymphocytic Lymphoma (SLL); Acute Myeloid Leukemia (AML); Mantle Cell Lymphoma (MCL); Diffuse Large B-cell Lymphoma (DLBCL); Follicular Lymphoma (FL); Marginal Zone Lymphoma (MZL)
• Intervention / Treatment: Drug: voruciclib monotherapy; Drug: voruciclib and venetoclax

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 Type: Interventional
• Enrollment (Actual): 84
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Duarte, California, United States, 91010
      • City of Hope
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern Memorial Hospital
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Dana Farber Cancer Institute
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic
  • Nebraska
    • Omaha, Nebraska, United States, 68198
      • University of Nebraska Medical Center
  • New York
    • New York, New York, United States, 10016
      • New York University
  • North Carolina
    • Durham, North Carolina, United States, 27705
      • Duke University
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health and Science University
  • Texas
    • Houston, Texas, United States, 77030
      • MD Anderson
  • Virginia
    • Charlottesville, Virginia, United States, 22903
      • University of Virginia
  • Washington
    • Seattle, Washington, United States, 98104
      • Swedish Cancer Institute
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Froedtert Hospital & the Medical College of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
Evaluate the PK of voruciclib	Determined by the Area Under the Concentration time curve (AUC)	2 years
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

Collaborators and Investigators

• Sponsor: MEI Pharma, Inc.
• Investigators: Study Director: Richard Ghalie, MD, MEI Pharma

Publications and helpful links

General Publications

• Alvarado-Valero Y, Cook RJ, Dinner SN, Keng M, Begna KH, Javidi-Sharifi N, Abedin S, Al Malki MM, Bhatt VR, Rajagopalan P, Tang M, Wiley SE, Ghalie RG, Davids MS. The oral CDK9 inhibitor voruciclib combined with venetoclax for patients with relapsed/refractory acute myeloid leukemia. Blood Neoplasia. 2025 Apr 25;2(3):100108. doi: 10.1016/j.bneo.2025.100108. eCollection 2025 Aug.
• Davids MS, Brander DM, Alvarado-Valero Y, Diefenbach CS, Egan DN, Dinner SN, Javidi-Sharifi N, Al Malki MM, Begna KH, Bhatt VR, Abedin S, Cook RJ, Collins MC, Roleder C, Dominguez EC, Rajagopalan P, Wiley SE, Ghalie RG, Danilov AV. A phase 1 study of the CDK9 inhibitor voruciclib in relapsed/refractory acute myeloid leukemia and B-cell malignancies. Blood Adv. 2025 Feb 25;9(4):820-832. doi: 10.1182/bloodadvances.2024014633.

Study record dates

Study Major Dates

• Study Start (Actual): May 31, 2018
• Primary Completion (Actual): July 24, 2024
• Study Completion (Actual): July 24, 2024

Study Registration Dates

• First Submitted: May 24, 2018
• First Submitted That Met QC Criteria: May 24, 2018
• First Posted (Actual): June 6, 2018

Study Record Updates

• Last Update Posted (Actual): March 17, 2026
• Last Update Submitted That Met QC Criteria: March 14, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: B-Cell Malignancies, AML, voruciclib, venetoclax
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Chronic Disease; Disease Attributes; Immune System Diseases; Neoplasms by Histologic Type; Hematologic Diseases; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Leukemia, B-Cell; Lymphoma, B-Cell; Lymphoma; Leukemia, Myeloid; Leukemia, Lymphoid; Leukemia; Pathological Conditions, Signs and Symptoms; Hemic and Lymphatic Diseases; Leukemia, Myeloid, Acute; Lymphoma, Large B-Cell, Diffuse; Leukemia, Lymphocytic, Chronic, B-Cell; Lymphoma, Follicular; Lymphoma, Mantle-Cell; Lymphoma, B-Cell, Marginal Zone; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; venetoclax; voruciclib
• Other Study ID Numbers: ME-522-001

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No