NCT03817320

PO Ixazomib in Combination With Chemotherapy for Childhood Relapsed or Refractory Acute Lymphoblastic Leukemia and Lymphoblastic Lymphoma

A TACL Phase 1/2 Study of PO Ixazomib in Combination With Chemotherapy for Childhood Relapsed or Refractory Acute Lymphoblastic Leukemia and Lymphoblastic Lymphoma IND# 140730

• Status: Active Not Recruiting
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 24 (actual)
• Sponsor: Therapeutic Advances in Childhood Leukemia Consortium · Academic / Other
• Sex: All
• Age: 1 Year – 21 Years
• Healthy volunteers: Not accepted

Summary

This is a phase 1/2 study of a drug called Ixazomib in combination with cytotoxic chemotherapy consisting of Vincristine, Dexamethasone, Asparaginase, and Doxorubicin (VXLD).

Detailed description

The phase 1 study is to determine the maximum tolerated dose (MTD) of the PO formulation, followed by a screening phase 2 study to investigate the efficacy of ixazomib in combination with chemotherapy in children with relapsed ALL and lymphoblastic lymphoma (LLy). The single arm, screening phase 2 design will allow us to use a minimal number of patients to obtain preliminary information about treatment efficacy. Discovering a safe and tolerable dose of ixazomib in a PO formulation and the preliminary efficacy data will significantly increase the possibility of ixazomib moving forward in frontline pediatric treatment protocols in both intense chemotherapy courses and maintenance courses.

Conditions

• ALL, Childhood
• Lymphoblastic Lymphoma, Childhood
• Lymphoblastic Leukemia, Acute, Childhood

Interventions

Type	Name	Description
DRUG	Ixazomib	Days 1, 4, 8, and 11. Note: at least 72 hours must have elapsed between doses Dose Phase 1 - Assigned upon study entry. Phase 2 - PO formulation at RP2D
DRUG	Vincristine	IV push over 1 minute or infusion via minibag as per institutional policy Days 1, 8, 15 and 22 Dose: ≥ 1 year: 1.5mg/m2/dose (maximum dose 2mg) ≥ 6 months and \< 1 year: 1.2mg/m2/dose \< 6 months: 1mg/m2/dose
DRUG	Dexamethasone	Days 1-14 Dose: ≥ 1 year: 10mg/m2/day, divided BID (i.e., 5mg/m2/dose, BID) ≥ 6 months and \< 1 year: 8mg/m2/day, divided BID (i.e., 4 mg/m2/dose, BID) \< 6 months: 7mg/m2/day, divided BID (i.e., 3.5 mg/m2/dose, BID)
DRUG	Asparaginase	Days 2, 15 Dose ≥ 1 year: 2,500 International units (IU)/m2/dose ≥ 6 months and \< 1 year: 2,000 IU/m2/dose \< 6 months: 1,750 IU/m2/dose Patient with allergic reaction to Pegaspargase can be given Erwinase IM/IV on Mon/Wed/Fri (or every other day per institutional standard) x 6 doses for each dose of Pegaspargase. Dosing guideline for Erwinase: * 1 year: 25,000 IU/m2/dose * 6 months and \< 1 year: 20,000 IU/m2/dose \< 6 months: 17,500 IU/m2/dose
DRUG	Doxorubicin	Day 1 Dose ≥ 1 year: 60mg/m2/dose ≥ 6 months and \< 1 year: 48 mg/m2/dose \< 6 months: 42mg/m2/dose
DRUG	Methotrexate (IT)	For patients with CNS 1 or CNS 2, on Days 1, 15, and 29
DRUG	Triple IT (Methotrexate, Hydrocortisone, Cytarabine)	For patients with CNS 3, on Days 1, 8, 15, 22, and 29
DRUG	Leucovorin	For patients with Down syndrome only, on Days 2, 9, 16, 23, and 30 (based on dates when IT Methotrexate or Triple IT is given)

Timeline

• Start date: 2019-02-12
• Primary completion: 2023-12-03
• Completion: 2025-06-30
• First posted: 2019-01-25
• Last updated: 2025-06-17
• Results posted: 2025-06-17

Locations

18 sites across 2 countries: United States, Australia

Regulatory

• FDA-regulated drug study