Treatment With ABT-199 (Venetoclax) and Purine Analogues in Relapsed/Refractory Acute Myeloid Leukemia

Study Overview
=================
Brief Summary
-----------------
Non-commercial, open-label interventional phase Ib study to assess the effectivity of the combination of venetoclax and 6-mercaptopurine in patients with relapsed or refractory AML.

Detailed Description
-----------------
Non-commercial, open-label interventional phase Ib study. The aim of the study is to assess the effectivity of the combination of venetoclax and 6-mercaptopurine in patients with relapsed or refractory AML.

Official Title
-----------------
ABT-199 (Venetoclax) and Purine Analogues as Novel Oral Drug Combination for Treatment of Relapsed/Refractory Acute Myeloid Leukemia: the ApoAML Trial

Conditions
-----------------
Acute Myeloid Leukemia, in Relapse, Acute Myeloid Leukemia Refractory

Intervention / Treatment
-----------------
* Drug: Venetoclax
* Drug: 6-mercaptopurine


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Relapsed or refractory AML Relapsed after or refractory to at least one cycle of intensive chemotherapy (combination of ara-c/anthracyclin) or four cycles of HMA (hypomethylating agents) Adult AML aged >/= 18 years WHO performance status: grade 0-2 at the time of enrollment ABT-199 (venetoclax) and PA-naïve. Patient may be prior exposed but not refractory to venetoclax. In case of previous therapy with venetoclax inclusion is only possible after discussion with the PI. Exclusion Criteria: Participation in any other interventional clinical trial during the study period Active presence (or known history of) central nervous system disease History or concomitant presence of any other malignancy, except for non-melanoma skin cancer, carcinoma in situ of the cervix, any other effectively treated malignancy that has been in remission for >5 years or that is highly likely to be cured at the time of enrollment. Active HIV, hepatitis B or hepatitis C infection Use of any antitumoral agent within less than 5 times the half-life of the agent prior to the screening bone marrow examination. After the screening bone marrow examination, the use of cytoreductive treatment prior to the initiation of venetoclax is permitted in order to lower the WBC-count to <25 000/µl (e.g. hydroxyurea). Medical conditions requiring chronic therapy of moderate or strong CYP3A4 inducers without alternative Patients with known hypersensitivity to the active substance or to any of the excipients Pregnant or breastfeeding woman Active uncontrolled systemic infection

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Venetoclax and 6-mercaptopurine<br>Single arm study with venetoclax and 6-mercaptopurine administered in two to six cycles of 28 days. Venetoclax is given at a dosage of 600mg with dose reduction in case of interaction with a moderate or strong CYP3A4 inhibitor. 6-mercaptopurine is given at a dosage of 100mg. | Drug: Venetoclax<br>* Venetoclax and 6-mercaptopurine<br>Drug: 6-mercaptopurine<br>* Venetoclax and 6-mercaptopurine<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical response | Objective response rate | at 2 months | 
| Clinical response | Objective response rate | at 6 months | 
| Clinical response | Objective response rate | at 2 years |