Study of the Safety and Pharmacokinetics of Venetoclax in Children and Young Adults with Relapsed or Refractory Malignancies

Phase 1

• Conditions: In Part 1 patients with any relapsed or refractory tumor will be eligible to enroll. During Part 2 patients with the following malignancies: acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), non-Hodgkin lymphoma (NHL), or neuroblastoma are eligle to enroll. In addition patients with any tumor that expresses BCL-2 can also enrol.; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2017-000439-14-NL
• Lead Sponsor: AbbVie Deutschland GmbH & Co. KG

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2017-08-14
• Last Update Posted: 8 January 2018

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 135

Inclusion Criteria

• Patients must be < 25 years of age.
o Enrollment of patients = 18 years of age may be halted at any time during the study to ensure adequate enrollment of pediatric patients (< 18 years).
• Patients must have relapsed or refractory cancer.
o Patients with high-risk neuroblastoma that is refractory after completion of at least 4 cycles of induction therapy (no response or stable disease as best response) are eligible to enroll in Part 2 (cohort expansion).
• Patients must have adequate hepatic function.
• Patient must have normal creatinine for age or have a calculated creatinine clearance = 60 mL/min/1.73 m2.
• Patients = 16 years of age must have performance status of Lansky = 50 and patients > 16 years of age must have performance status of Karnofsky > 50%.
• Patients with solid tumors must have adequate bone marrow function as defined by ANC = 1000/µl and platelets > 75,000/µl (with transfusion independence defined as not receiving platelet transfusion within 7 days prior to enrollment).
• For the fifth cohort during Part 2, patients with solid tumors must have evidence of BCL-2 expression.
Are the trial subjects under 18? yes
Number of subjects for this age range: 115
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 20
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

• Patients with primary brain tumors or disease metastatic to the brain.
• For patients with leukemia, has overt CNS disease (CNS 3 status) as defined by CSF WBC > 5/hpf with blasts on cytospin or any cranial nerve palsy regardless of cell count.
• Patients who have received any of the following within the listed time frame, prior to the first dose of study drug
o Biologic agent (i.e., antibodies) for anti-neoplastic intent within 30 days
o CAR-T infusion or other cellular therapy within 30 days
o Anticancer therapy including blinatumomab or chemotherapy, radiation therapy, targeted small molecule agents, investigational agents within 14 days or 5 half-lives, whichever is shorter
o Steroid therapy for anti-neoplastic intent within 5 days
o Requires ongoing hydroxyurea (hydroxyurea permitted up to first dose)
• Patients who are less than 100 days post-transplant, or = 100 days post-transplant with active GVHD, or are receiving immunosuppressant therapy within 7 days prior to first dose of study drug.
• Patients who are less than 6 weeks post-131 I-mIBG therapy.
• Patients who have received the following within 7 days prior to the first dose of study drug:
o Strong and moderate CYP3A inhibitors (Part 1);
o Strong and moderate CYP3A inducers (Part 1 and Part 2).
• Patients who have not recovered from clinically significant adverse effect(s)/toxicity(s) of the previous therapy.
• Patients who have active, uncontrolled infections.
Patients with malabsorption syndrome or any other condition that precludes enteral administration.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: Evaluate the safety of venetoclax monotherapy.<br>Determine dose limiting toxicities (DLT) and the recommended Phase 2 dose (RPTD) of venetoclax monotherapy.<br>Assess the pharmacokinetics (PK) of venetoclax monotherapy.<br>;Secondary Objective: Determine the preliminary efficacy of venetoclax as monotherapy.<br>Evaluate the safety of venetoclax in combination with chemotherapy.<br> Assess the preliminary efficacy of venetoclax in combination with chemotherapy.;Primary end point(s): - Safety<br>- Dose Limiting Toxicities (DLT)<br>- Pharmacokinetics (PK);Timepoint(s) of evaluation of this end point: - 9 months<br>- 21 days<br>- 9 months

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): - Objective Response Rate <br>- Complete Response Rate <br>- Partial Response Rate ;Timepoint(s) of evaluation of this end point: - First Evaluation at 21 days for AML and ALL and then throughout the study <br>- First Evaluation at Week 8 for Non-Hodgkin’s Lymphoma, Neuroblastoma and other solid tumors and then throughout the study.