Acute Lymphoblastic Leukemia (ALL), Acute Myeloid Leukemia (AML), Malignancies, Neuroblastoma, Non-Hodgkin's Lymphoma
Conditions
Keywords
Cancer, Venetoclax, pediatric, relapsed or refractory, Venclexta
Brief summary
An open-label, global, multi-center study to evaluate the safety and pharmacokinetics of venetoclax monotherapy, to determine the dose limiting toxicity (DLT) and the recommended Phase 2 dose (RPTD), and to assess the preliminary efficacy of venetoclax in pediatric and young adult participants with relapsed or refractory malignancies.
Interventions
DRUGchemotherapy
Dexamethasone and/or vincristine and/or pegasparaginase OR cytarabine and/or etoposide and/or pegasparaginase; tyrosine kinase inhibitor; cytarabine OR azacitidine OR decitabine; rituximab and/or dexamethasone and/or vincristine; cyclophosphamide and/or topotecan
DRUGvenetoclax
Oral tablet for participants; Tablet for oral suspension (participants who cannot swallow a tablet)
Sponsors
Roche-Genentech
AbbVie
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
0 Years to 25 Years
Healthy volunteers
No
Inclusion criteria
* Participants must have relapsed or refractory cancer. * Participants must have adequate hepatic and kidney function. * Participants less than or equal to 16 years of age must have performance status of Lansky greater than or equal to 50% and participants greater than 16 years of age must have performance status of Karnofsky greater than or equal to 50%. * Participants with solid tumors (with the exception of neuroblastoma) must have adequate bone marrow function in Part 1. * For the fifth cohort during Part 2 Cohort Expansion, participants with solid tumors must have evidence of BCL-2 expression (except participants with TCF3-HLF ALL).
Exclusion criteria
* Participants with primary brain tumors or disease metastatic to the brain. * Participants who have central nervous system (CNS) disease with cranial involvement that requires radiation. * Participants who have received any of the following within the listed time frame, prior to the first dose of study drug * Inotuzumab ozogamicin or gemtuzumab ozogamicin within 30 days * Biologic agent (i.e., antibodies) for anti-neoplastic intent within 30 days or 5 half-lives whichever is shorter. * CAR-T infusion or other cellular therapy within 30 days * Anticancer therapy including chemotherapy, radiation therapy, targeted small molecule agents, investigational agents within 14 days or 5 half-lives, whichever is shorter (Exceptions: Ph+ALL participants on Tyrosine Kinase Inhibitor (TKI) at Screening may enroll and remain on TKI therapy to control disease and TCF3-HLF ALL participants are allowed to have received chemotherapy within 14 days or 5 half-lives, whichever is shorter). * Steroid therapy for anti-neoplastic intent within 5 days (with the exception of TCF3-HLF ALL participants). * Requires ongoing hydroxyurea (hydroxyurea permitted up to first dose) * Participants who are less than 100 days post-transplant, or greater than or equal to 100 days post-transplant with active graft versus host disease (GVHD), or are receiving immunosuppressant therapy within 7 days prior to first dose of study drug. * Participants who are less than 6 weeks post-131 I-metaiodobenzylguanidine (mIBG) therapy. * Participants who have received the following within 7 days prior to the first dose of study drug: * Strong and moderate Cytochrome P450 3A (CYP3A) inhibitors (Part 1 Dose Determination); * Strong and moderate CYP3A inducers (Part 1 Dose Determination and Part 2 Cohort Expansion). * Participants who have not recovered from clinically significant adverse effect(s)/toxicity(s) of the previous therapy (Exception: Chemotherapy induced side effects that are expected to return to baseline in TCF3-HLF ALL participants). * Participants who have active, uncontrolled infections. * Participants with malabsorption syndrome or any other condition that precludes enteral administration. * Participants with recent positive test for SARS-CoV-2 (COVID-19) and no follow up test with negative result cannot be enrolled. Participants with contact to persons with COVID-19 and participants with signs and symptoms for COVID-19 infection must be tested before enrolling.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| AUC0-24 Post-Dose of Venetoclax | Up to approximately 2 weeks | Area under the plasma concentration-time curve from 0 to 24 hours (AUC24) post-dose of venetoclax. |
| Recommended Phase 2 dose (RPTD) of Venetoclax | First 21 days venetoclax monotherapy | Venetoclax RPTD is the dose determined based on adverse event reporting and dose-limiting toxicity information from all participants. |
| Cmax of Venetoclax | Up to approximately 2 weeks | Maximum plasma concentration (Cmax) of venetoclax. |
| Tmax of venetoclax | Up to approximately 2 weeks | Time to maximum plasma concentration (Tmax) of venetoclax. |
| Number of Participants Experiencing Adverse Events | Up to 9 months | An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product which does not necessarily have a causal relationship with this treatment. The investigator assesses the relationship of each event to the use of study. |
| Number of Participants With Dose Limiting Toxicities (DLT) of Venetoclax Monotherapy | First 21 days venetoclax monotherapy | A DLT is any Grade 3 or higher non-hematologic adverse event (AE) with exceptions outlined in the protocol. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Partial Response (PR) Rate | Up to 9 months | PR is defined according to established criteria for each tumor type and is described in detail within the study protocol. |
| Complete Response (CR) Rate | Up to 9 months | CR is defined according to established criteria for each tumor type and is described in detail within the study protocol. |
| Objective Response Rate (ORR) | Up to 9 months | ORR is defined as the proportion of participants who achieved a response according to established criteria described in detail in the study protocol. |
Countries
Australia, Canada, France, Germany, Netherlands, Switzerland, United Kingdom, United States
Outcome results
None listed