A Phase 1 Study of the Safety and Pharmacokinetics of Venetoclax in Pediatric and Young Adult Patients with Relapsed or Refractory Malignancies
- Conditions
- on-Hodgkin lymfomen, neuroblastoom en overige solide tumorenAML/ALL/NHL/NeuroblastomaPediatric cancer10024324
- Registration Number
- NL-OMON50736
- Lead Sponsor
- AbbVie B.V.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 4
1. 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).
2. 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).
o Patients with confirmed diagnosis of TCF3-HLF ALL are eligible to enroll in
the 5th cohort in Part 2 (cohort expansion) beginning on or after Day 15 of
induction or the end of induction and will be assessed independently of other
subject with ALL.
3. Patients must have adequate hepatic function.
4. Patient must have normal creatinine for age or have a calculated creatinine
clearance >= 60 mL/min/1.73 m2.
5. 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%.
6. In Part I, patients with solid tumors (with the exception of neuroblastoma)
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).
7. For the fifth cohort during Part 2, patients with solid tumors must have
evidence of BCL-2 expression.
1. Patients with primary brain tumors or disease metastatic to the brain.
2. Patients who have CNS disease with cranial involvement that requires
radiation.
3. Patients who have received any of the following within the listed time
frame, prior to the first dose of study drug
- Inotuzumab ozogamicin within 30 days
- Biologic agent (i.e., antibodies) for anti-neoplastic intent within 30 days
- CAR-T infusion or other cellular therapy within 30 days
- Anticancer therapy including blinatumomab or chemotherapy, radiation therapy,
targeted small molecule agents, investigational agents within 14 days or 5
half-lives, whichever is shorter
- Exceptions: Ph+ ALL subjects on TKIs at Screening may enroll and remain
on TKI
therapy to control disease.
- Steroid therapy for anti-neoplastic intent within 5 days
- Requires ongoing hydroxyurea (hydroxyurea permitted up to first dose)
4. 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.
5. Patients who are less than 6 weeks post-131 I-mIBG therapy.
6. Patients who have received the following within 7 days prior to the first
dose of study drug:
- Strong and moderate CYP3A inhibitors (Part 1);
- Strong and moderate CYP3A inducers (Part 1 and Part 2).
7. Patients who have not recovered from clinically significant adverse
effect(s)/toxicity(s) of the previous therapy.
8. Patients who have active, uncontrolled infections.
9. Patients with malabsorption syndrome or any other condition that precludes
enteral administration.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Safety: Safety will be assessed by evaluating study drug exposure, adverse<br /><br>events, serious adverse events, deaths, and changes from baseline in laboratory<br /><br>determinations. Safety summaries will be provided for Part 1 and Part 2<br /><br>separately and overall, and by dose level, tumor type and combination therapy<br /><br>(venetoclax in combination with chemotherapy).<br /><br><br /><br>Pharmacokinetic: Plasma concentrations of venetoclax (and metabolite(s)) and<br /><br>pharmacokinetic parameter values will be tabulated for each patient and each<br /><br>dose level. Summary statistics will be provided for each sampling time and each<br /><br>parameter.</p><br>
- Secondary Outcome Measures
Name Time Method <p>- Objective Response Rate<br /><br>- Complete Response Rate<br /><br>- Partial Response Rate</p><br>