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

NCT ID: NCT03547115

Last Updated: 2023-08-07

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE1

Total Enrollment

100 participants

Study Classification

INTERVENTIONAL

Study Start Date

2018-05-31

Study Completion Date

2025-03-31

Brief Summary

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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

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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.

Conditions

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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)

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

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.
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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

Group Type EXPERIMENTAL

voruciclib monotherapy

Intervention Type DRUG

Voruciclib will be administered orally

voruciclib and venetoclax

Intervention Type DRUG

Voruciclib and Venetoclax will be administered orally

Interventions

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voruciclib monotherapy

Voruciclib will be administered orally

Intervention Type DRUG

voruciclib and venetoclax

Voruciclib and Venetoclax will be administered orally

Intervention Type DRUG

Other Intervention Names

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ME-522 VENCLEXTA® ME-522

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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MEI Pharma, Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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City of Hope

Duarte, California, United States

Site Status RECRUITING

Northwestern Memorial Hospital

Chicago, Illinois, United States

Site Status RECRUITING

Dana Farber Cancer Institute

Boston, Massachusetts, United States

Site Status ACTIVE_NOT_RECRUITING

Mayo Clinic

Rochester, Minnesota, United States

Site Status RECRUITING

University of Nebraska Medical Center

Omaha, Nebraska, United States

Site Status RECRUITING

New York University

New York, New York, United States

Site Status ACTIVE_NOT_RECRUITING

Duke University

Durham, North Carolina, United States

Site Status ACTIVE_NOT_RECRUITING

Oregon Health and Science University

Portland, Oregon, United States

Site Status RECRUITING

MD Anderson

Houston, Texas, United States

Site Status RECRUITING

University of Virginia

Charlottesville, Virginia, United States

Site Status RECRUITING

Swedish Cancer Institute

Seattle, Washington, United States

Site Status ACTIVE_NOT_RECRUITING

Froedtert Hospital & the Medical College of Wisconsin

Milwaukee, Wisconsin, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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MEI Pharma

Role: CONTACT

858-369-7100

References

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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.

Reference Type DERIVED
PMID: 40809193 (View on PubMed)

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.

Reference Type DERIVED
PMID: 39705540 (View on PubMed)

Other Identifiers

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ME-522-001

Identifier Type: -

Identifier Source: org_study_id

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