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

MEI Pharma

Status and phase: Enrolling; Phase 1

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

Treatments: Drug: voruciclib and venetoclax; Drug: voruciclib monotherapy

Study type: Interventional

Funder types: Industry

Identifiers

NCT03547115

ME-522-001

Details and patient eligibility

About

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

Full 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.

Enrollment: 100 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No 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

  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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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100 participants in 1 patient group

voruciclib monotherapy and voruciclib in combination with venetoclax

Experimental group

Description:

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

Treatment:

Drug: voruciclib monotherapy

Drug: voruciclib and venetoclax