NCT05157971

Venetoclax and a Pediatric-Inspired Regimen for the Treatment of Newly Diagnosed B Cell Acute Lymphoblastic Leukemia

A Phase 1 Study Combining Venetoclax With a Pediatric-Inspired Regimen for Newly Diagnosed Adults With B Cell Ph-Like Acute Lymphoblastic Leukemia

• Status: Recruiting
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 24 (estimated)
• Sponsor: City of Hope Medical Center · Academic / Other
• Sex: All
• Age: 18 Years – 54 Years
• Healthy volunteers: Not accepted

Summary

This phase I trial tests the safety, side effects, and best dose of venetoclax in combination with a pediatric-inspired chemotherapy regimen known as C10403 in treating patients with newly diagnosed B cell acute lymphoblastic leukemia. Venetoclax may stop the growth of cancer cells by blocking Bcl-2, a protein needed for cancer cell survival. The C10403 regimen is composed of the chemotherapy drugs cytarabine, cyclophosphamide, daunorubicin, mercaptopurine, pegaspargase, vincristine, and methotrexate, all which work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. It also consists of prednisone, which is an anti-inflammatory drug that lowers the body's immune response and is used with other drugs in the treatment of some types of some types of cancer. This study may help researchers learn if adding venetoclax to the pediatric-inspired C10403 regimen can be tolerated and help treat older patients.

Detailed description

PRIMARY OBJECTIVES: I. To assess the safety and tolerability of combining venetoclax with the C10403 regimen backbone during induction and consolidation in newly diagnosed adults with B cell acute lymphoblastic leukemia (ALL). II. To determine the maximum tolerated dose (MTD) and the recommended phase 2 dose/schedule (RP2D) of venetoclax in combination with the C10403 regimen. SECONDARY OBJECTIVES: I. To estimate complete response (CR) after induction. II. To estimate composite CR (CR or CR with incomplete hematologic recovery \[CRi\] or CR with partial hematologic recovery \[CRh\]) after induction. III. To estimate minimal residual disease (MRD) negativity after induction. IV. To estimate MRD negativity after consolidation. V. To estimate CR after induction for Philadelphia (Ph)-like ALL. VI. To estimate CR/CRi/CRh after induction for Ph-like ALL. VII. To estimate MRD negativity after induction for Ph-like ALL. VIII. To estimate MRD negativity after consolidation for Ph-like ALL. IX. To estimate leukemia-free survival (LFS) and overall survival (OS). OUTLINE: INDUCTION: Patients receive venetoclax orally (PO) on days 1-14. Patients also receive cytarabine intrathecally (IT) on day 1, prednisone PO twice daily (BID) on days 1-28, vincristine intravenously (IV) on days 1, 8, 15 and 22, daunorubicin IV on days 1, 8, 15 and 22, pegaspargase intramuscularly (IM) or IV on day 4, and methotrexate IT on days 8 and 29 (and also on days 15 and 22 for central nervous system \[CNS\]3 patients) in the absence of disease progression or unacceptable toxicity. Patients with stable disease (SD) or partial response (PR) after Induction proceed to Extended Induction. Patients with CR, CRi, or CRh after Induction proceed to Consolidation. EXTENDED INDUCTION: Patients receive venetoclax PO on days 1-7, prednisone PO BID on days 1-14, vincristine IV on days 1 and 8, daunorubicin IV on day 1, and pegaspargase IM or IV on day 4 in the absence of disease progression or unacceptable toxicity. Patients with CR, CRi, or CRh after Extended Induction proceed to Consolidation. CONSOLIDATION: Patients receive venetoclax PO on days 1-14, cyclophosphamide IV on days 1 and 29, cytarabine IV or subcutaneously (SC) on days 1-4, 8-11, 29-32 and 36-39, mercaptopurine PO on days 1-14 and 29-42, vincristine IV on days 15, 22, 43 and 50, pegaspargase IM or IV on days 15 and 43, and methotrexate IT on days 1, 8, 15 and 22 (omit on days 15 and 22 for CNS3 patients) in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up at 30 days, then every 3 months for 1 year.

Conditions

• B Acute Lymphoblastic Leukemia
• Ph-Like Acute Lymphoblastic Leukemia

Interventions

Type	Name	Description
DRUG	Cyclophosphamide	Given IV
DRUG	Cytarabine	Given SC, IV or IT
DRUG	Daunorubicin Hydrochloride	Given IV
DRUG	Mercaptopurine	Given PO
DRUG	Methotrexate	Given IT
DRUG	Pegaspargase	Given IM or IV
DRUG	Prednisone	Given PO
DRUG	Venetoclax	Given PO
DRUG	Vincristine Sulfate	Given IV

Timeline

• Start date: 2022-03-17
• Primary completion: 2026-05-12
• Completion: 2026-05-12
• First posted: 2021-12-15
• Last updated: 2026-03-05

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study