A Study to Assess the Effect of Venetoclax on Ethinyl Estradiol and Levonorgestrel in Female Participants With Different Hematological Malignancies

Study Overview
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Brief Summary
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A study to assess the effect of multiple doses of venetoclax on the pharmacokinetics of ethinyl estradiol and levonorgestrel in female participants with different hematological malignancies. Upon completion of this study, participants receiving clinical benefit in the opinion of the investigator and without any clinically significant evidence of disease progression with no access to venetoclax (not approved for the treated indication) may continue receiving venetoclax at the discretion of the investigator in a separate extension study.

Official Title
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A Study to Assess the Effect of Venetoclax on the Pharmacokinetics of Ethinyl Estradiol/Levonorgestrel in Female Subjects With Hematologic Malignancies

Conditions
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Hematologic Malignancies

Intervention / Treatment
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* Drug: Venetoclax
* Drug: ethinyl estradiol/levonorgestrel


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participant must have relapsed or refractory non-Hodgkin's lymphoma (NHL). Participant must have histologically documented diagnosis of one of the following NHL subtypes: diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), lymphoplasmacytic lymphoma (LPL), mantle cell lymphoma (MCL), marginal zone lymphoma (MZL), T-cell prolymphocytic lymphoma (T-PLL), Waldenström's macroglobulinemia (WM) Has an Eastern Cooperative Oncology Group (ECOG) performance score of less than or equal to two. Must have adequate bone marrow, coagulation, renal and hepatic function as described in the protocol. A female of non-childbearing potential as described in the protocol. Exclusion Criteria: History of currently active, clinically significant cardiovascular disease. If the participant has had prior stem cell transplantation, it must have been more than 100 days prior to start of study drug, with no graft versus host disease, and no immunosuppression therapy. evidence of transformation of the lymphoma immediately prior to study entry. Evidence of central nervous system involvement by lymphoma.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ethinyl estradiol/Levonorgestrel and Venetoclax<br>Ethinyl estradiol/levonorgestrel is administered on Period 1 Day 1 and then again on Period 3 Day 1. Venetoclax is administered on Period 2 Day 1 and then daily thereafter. | Drug: Venetoclax<br>* tablet; oral<br>* Other names: Venclexta;Drug: ethinyl estradiol/levonorgestrel<br>* tablet; oral<br>* Other names: Levora;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tmax of Venetoclax | Time to maximum plasma concentration (Tmax) of Venetoclax. | Up to approximately 59 days after initial study drug dose | 
| Tmax of (ethinyl estradiol) EE/Levonorgestrel | Time to maximum plasma concentration (Tmax) of EE/Levonorgestrel | Up to approximately 59 days after initial study drug dose | 
| Cmax of Venetoclax | Maximum plasma concentration (Cmax) of Venetoclax | Up to approximately 59 days after initial study drug dose | 
| Cmax of EE/Levonorgestrel | Maximum plasma concentration (Cmax) of EE/Levonorgestrel | Up to approximately 59 days after initial study drug dose | 
| t1/2 of Venetoclax | Terminal phase elimination half-life (t1/2) of Venetoclax. | Up to approximately 59 days after initial study drug dose | 
| t1/2 of EE/Levonorgestrel | Terminal phase elimination half-life (t1/2) of EE/Levonorgestrel | Up to approximately 59 days after initial study drug dose | 
| AUCt of Venetoclax | Area under the plasma concentration-time curve (AUC) from time 0 to time of the last measurable concentration (AUCt) of Venetoclax | Up to approximately 59 days after initial study drug dose | 
| AUCt of EE/Levonorgestrel | Area under the plasma concentration-time curve (AUC) from time 0 to time of the last measurable concentration (AUCt) of EE/Levonorgestrel | Up to approximately 59 days after initial study drug dose | 
| AUCinf of EE/Levonorgestrel | AUC from time 0 extrapolated to infinite time (AUCinf) of EE/Levonorgestrel. | Up to approximately 59 days after initial study drug dose | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cancer, Hematologic Malignancies, venetoclax, ethinyl estradiol, relapsed or refractory non-Hodgkin's lymphoma, non-Hodgkin's lymphoma