A Phase 1 Study of the Safety and Pharmacokinetics of Venetoclax in Pediatric and Young Adult Patients with Relapsed or Refractory Malignancies

Protocol # :
Acute Lymphoblastic Leukemia (ALL)
Acute Myeloid Leukemia (AML)
Non-Hodgkin's Lymphoma
Disease Sites
Lip, Oral Cavity and Pharynx
Small Intestine
Other Digestive Organ
Other Respiratory and Intrathoracic Organs
Bones and Joints
Soft Tissue
Mycosis Fungoides
Other Skin
Corpus Uteri
Other Female Genital
Other Male Genital
Urinary Bladder
Other Urinary
Eye and Orbit
Brain and Nervous System
Other Hematopoietic
Unknown Sites
Ill-Defined Sites
Other Endocrine System
Non-Hodgkin's Lymphoma
Hodgkin's Lymphoma
Multiple Myeloma
Lymphoid Leukemia
Myeloid and Monocytic Leukemia
Leukemia, other
Kaposi's Sarcoma
Melanoma, Skin
Principal Investigator
Place, Andrew, E
Site Research Nurses
Braun, Christine
Cuttle, Annette, B.
Ezrre, Suzanne
Ranaghan, Emily

Trial Description

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.

Eligibility Requirements

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)

- 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

- Strong and moderate CYP3A inducers (Part 1 Dose Determination and Part 2 Cohort

- 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

- 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.