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

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).

Conditions

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

Interventions

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)

Sponsors & Collaborators

• Takeda

  collaborator INDUSTRY

• Children's Hospital Los Angeles

  collaborator OTHER

• Therapeutic Advances in Childhood Leukemia Consortium

  lead OTHER

Principal Investigators

• Terzah Horton, MD · Baylor College of Medicine

Study Design

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Min Age

1 Year

Max Age

21 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2019-02-12

Primary Completion

2023-12-03

Completion

2025-06-30

FDA Drug

Yes

Countries

• United States
• Australia

Study Locations