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

NCT03547115 | Terminated Phase 1 FDA Drug

• 1 other identifier: ME-522-001
• Study Type: interventional
• Target: 84
• Locations: 1 country
• Sites: 12

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

Conditions

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

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (5)

• Overall Response Rate (ORR)

  2 years

• Duration of Response (DOR)

  2 years

• Progression Free Survival (PFS)

  2 years

• Evaluate the PK of voruciclib

  2 years

• Evaluate the PK of voruciclib Cmax in combination with venetoclax Determined by the Area Under the Concentration time curve (AUC)

  2 years

Study Arms (1)

voruciclib monotherapy and voruciclib in combination with venetoclax

EXPERIMENTAL

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; Drug: voruciclib and venetoclax

Interventions

voruciclib monotherapy DRUG

Voruciclib will be administered orally

Also known as: ME-522

voruciclib monotherapy and voruciclib in combination with venetoclax

voruciclib and venetoclax DRUG

Voruciclib and Venetoclax will be administered orally

Also known as: VENCLEXTA®, ME-522

voruciclib monotherapy and voruciclib in combination with venetoclax

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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:

Sponsors & Collaborators

• MEI Pharma, Inc.: lead

Study Sites (12)

City of Hope

Duarte, California, 91010, United States

Location

Northwestern Memorial Hospital

Chicago, Illinois, 60611, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

University of Nebraska Medical Center

Omaha, Nebraska, 68198, United States

Location

New York University

New York, New York, 10016, United States

Location

Duke University

Durham, North Carolina, 27705, United States

Location

Oregon Health and Science University

Portland, Oregon, 97239, United States

Location

MD Anderson

Houston, Texas, 77030, United States

Location

University of Virginia

Charlottesville, Virginia, 22903, United States

Location

Swedish Cancer Institute

Seattle, Washington, 98104, United States

Location

Froedtert Hospital & the Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

Related Publications (2)

• 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.

  PMID: 40809193 RESULT

• 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.

  PMID: 39705540 RESULT

MeSH Terms

Conditions

Lymphoma, Follicular; Lymphoma, Mantle-Cell; Lymphoma, B-Cell, Marginal Zone; Leukemia, Lymphocytic, Chronic, B-Cell; Lymphoma, Large B-Cell, Diffuse; Leukemia, Myeloid, Acute

Interventions

voruciclib; venetoclax

Condition Hierarchy (Ancestors)

Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Lymphoma, B-Cell; Leukemia, B-Cell; Leukemia, Lymphoid; Leukemia; Hematologic Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Leukemia, Myeloid

Study Officials

• Richard Ghalie, MD

  MEI Pharma

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: May 24, 2018
• First Posted: June 6, 2018
• Study Start: May 31, 2018
• Primary Completion: July 24, 2024
• Study Completion: July 24, 2024
• Last Updated: March 17, 2026

Record last verified: 2026-03

Locations

US (12)