Description:
This is a Phase 1, open-label, 3 + 3 dose escalation study to determine the safety and
preliminary efficacy of voruciclib in subjects with relapsed/refractory B cell malignancies
and AML after treatment with standard therapy.
Title
- Brief Title: A Phase 1 Study of Voruciclib in Subjects With B-Cell Malignancies or AML
- Official Title: A Phase 1, Open-label, Study of Voruciclib in Subjects With Relapsed and/or Refractory B Cell Malignancies or Acute Myeloid Leukemia After Failure of Prior Standard Therapies
Clinical Trial IDs
- ORG STUDY ID:
ME-522-001
- NCT ID:
NCT03547115
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)
Interventions
Drug | Synonyms | Arms |
---|
voruciclib | | voruciclib |
Purpose
This is a Phase 1, open-label, 3 + 3 dose escalation study to determine the safety and
preliminary efficacy of voruciclib in subjects with relapsed/refractory B cell malignancies
and AML after treatment with standard therapy.
Detailed Description
This is a Phase 1, open-label, 3 + 3 dose escalation study to determine the safety and
preliminary efficacy of voruciclib in subjects with relapsed/refractory B cell malignancies
and AML after treatment with standard therapy. Escalation to the next higher dose level will
depend on demonstrated safety and tolerability at each dose level.
Subjects may continue to receive voruciclib while there is evidence of clinical benefit and
acceptable toxicity as judged by the investigator.
Trial Arms
Name | Type | Description | Interventions |
---|
voruciclib | Experimental | 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) | |
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
- Ongoing immunosuppressive treatment at the time of the start of voruciclib therapy,
including systemic or enteric corticosteroids except as follows:
1. Prior to the start of voruciclib therapy, 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
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | Determine the safety and tolerability of voruciclib |
Time Frame: | 2 years |
Safety Issue: | |
Description: | 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) |
Secondary Outcome Measures
Measure: | Overall Response Rate (ORR) |
Time Frame: | 2 years |
Safety Issue: | |
Description: | 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 |
Measure: | Duration of Response (DOR) |
Time Frame: | 2 years |
Safety Issue: | |
Description: | defined as the time from the initial determination of response to the time of disease progression or death on study, which ever occurs first |
Measure: | Rate of CR/CRi |
Time Frame: | 2 years |
Safety Issue: | |
Description: | defined as the proportion of subjects with CR and CRi (i.e 2 CRs or CRis at least 28 days apart) according to IWG criteria |
Measure: | Progression Free Survival (PFS) |
Time Frame: | 2 years |
Safety Issue: | |
Description: | 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 |
Measure: | Evaluate the PK of voruciclib |
Time Frame: | 2 years |
Safety Issue: | |
Description: | Determined by the Area Under the Concentration time curve (AUC) |
Measure: | Evaluate the PK of voruciclib Cmax |
Time Frame: | 2 years |
Safety Issue: | |
Description: | Determined by Peak Plasma Concentration (Cmax) |
Details
Phase: | Phase 1 |
Primary Purpose: | Interventional |
Overall Status: | Recruiting |
Lead Sponsor: | MEI Pharma, Inc. |
Trial Keywords
- B-Cell Malignancies, AML, voruciclib, Cyclin Dependent Kinase Inhibitor
Last Updated
November 6, 2020