Clinical trial NCT03547115: A Study of Voruciclib Alone or in Combination With Venetoclax in Subjects With B-Cell Malignancies or AML
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
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, CDK Inhibitor
Lead sponsor: MEI Pharma, Inc.
Sponsor class: INDUSTRY
First posted: 2018-06-06
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
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.
Primary purpose: TREATMENT

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

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.

Eligibility criteria: 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

Primary outcomes:
measure: Determine the safety and tolerability of voruciclib
timeFrame: 2 years
measure: Determine the safety and tolerability of voruciclib in combination with venetoclax in subjects with AML.
timeFrame: 2 years
Secondary outcomes:
measure: Overall Response Rate (ORR)
timeFrame: 2 years
measure: Duration of Response (DOR)
timeFrame: 2 years
measure: Progression Free Survival (PFS)
timeFrame: 2 years
measure: Evaluate the PK of voruciclib
timeFrame: 2 years
measure: Evaluate the PK of voruciclib Cmax in combination with venetoclax Determined by the Area Under the Concentration time curve (AUC)
timeFrame: 2 years
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope
state: California
city: Chicago
country: United States
facility: Northwestern Memorial Hospital
state: Illinois
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Omaha
country: United States
facility: University of Nebraska Medical Center
state: Nebraska
city: New York
country: United States
facility: New York University
state: New York
city: Durham
country: United States
facility: Duke University
state: North Carolina
city: Portland
country: United States
facility: Oregon Health and Science University
state: Oregon
city: Houston
country: United States
facility: MD Anderson
state: Texas
city: Charlottesville
country: United States
facility: University of Virginia
state: Virginia
city: Seattle
country: United States
facility: Swedish Cancer Institute
state: Washington
city: Milwaukee
country: United States
facility: Froedtert Hospital & the Medical College of Wisconsin
state: Wisconsin
Study officials:
References: