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
1 other identifier
interventional
24
2 countries
18
Brief 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).
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_1
Started Feb 2019
Longer than P75 for phase_1
18 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
January 22, 2019
CompletedFirst Posted
Study publicly available on registry
January 25, 2019
CompletedStudy Start
First participant enrolled
February 12, 2019
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 3, 2023
CompletedResults Posted
Study results publicly available
June 17, 2025
CompletedStudy Completion
Last participant's last visit for all outcomes
June 30, 2025
CompletedJune 17, 2025
May 1, 2025
4.8 years
January 22, 2019
March 7, 2025
May 30, 2025
Conditions
Outcome Measures
Primary Outcomes (2)
Phase 1: Dose Limiting Toxicity (DLT) During Block 1 of Chemotherapy
The incidence of dose limiting toxicity (DLT) will be measured only during block 1
5 weeks
Phase 2: Response (CR + CR MRD-, and CR + CR MRD- + CRi) After Block 1 Chemotherapy at the RP2D
The count of participants below represents the number of patients who achieved CR MRD- or CRi MRD- at the end of block 1 treatment and treated at RP2D (recommended phase 2 dose).
End of Block 1 treatment, Day 29-35 of treatment, assessed within 35 days from treatment start
Study Arms (4)
Ixazomib Dose Level 1 (Stratum A)
EXPERIMENTALPatients will be treated on ixazomib at 1.6 mg/m\^2/day on Days 1, 4, 8, and 11. Vincristine IV at 1.5 mg/m\^2 on Days 1, 8, 15 and 22. Pegaspargase IV/IM at 2500 IU/m\^2 on Days 2 and 15, Doxorubicin at 60 mg/m\^2 on Days 1, Dexamethasone IV/PO at 10 mg/m\^2 continuous starting on Day 1 thru Day 14, and IT chemotherapy dependent on patient's CNS status at time of enrollment. This arm is the starting Dose Level for patients being enrolled.
Ixazomib Dose Level 2 (Stratum A)
EXPERIMENTALPatients will be treated on ixazomib at 2.0 mg/m\^2/day on Days 1, 4, 8, and 11. Vincristine IV at 1.5 mg/m\^2 on Days 1, 8, 15 and 22. Pegaspargase IV/IM at 2500 IU/m\^2 on Days 2 and 15, Doxorubicin at 60 mg/m\^2 on Days 1, Dexamethasone IV/PO at 10 mg/m\^2 continuous starting on Day 1 thru Day 14, and IT chemotherapy dependent on patient's CNS status at time of enrollment. Patients will be treated at this arm Dose Level once patient accrual at Dose Level 1 has been completed and dose escalation is allowed as defined by the 3+3 design.
Ixazomib Dose Level -1 (Stratum A)
EXPERIMENTALPatients will be treated on ixazomib at 1.2 mg/m\^2/day on Days 1, 4, 8, and 11. Vincristine IV at 1.5 mg/m\^2 on Days 1, 8, 15 and 22. Pegaspargase IV/IM at 2500 IU/m\^2 on Days 2 and 15, Doxorubicin at 60 mg/m\^2 on Days 1, Dexamethasone IV/PO at 10 mg/m\^2 continuous starting on Day 1 thru Day 14, and IT chemotherapy dependent on patient's CNS status at time of enrollment. This arm Dose Level -1 is needed only if de-escalation from Dose Level 1 is required.
Ixazomib Dose Level 1 (Stratum B)
EXPERIMENTALPatients will be treated on ixazomib at 1.6 mg/m\^2/day on Days 1, 4, 8, and 11. Vincristine IV at 1.5 mg/m\^2 on Days 1, 8, 15 and 22. Pegaspargase IV/IM at 2500 IU/m\^2 on Days 2 and 15, Doxorubicin at 60 mg/m\^2 on Days 1, Dexamethasone IV/PO at 10 mg/m\^2 continuous starting on Day 1 thru Day 14, and IT chemotherapy dependent on patient's CNS status at time of enrollment. Leucovorin PO/IV at 5 mg/m\^2/dose X 2 doses given 24 and 30 hours after IT Methotrexate or Triple IT will also be given on this arm. This arm is only for patients with Down syndrome (Stratum B).
Interventions
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
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
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)
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
Day 1 Dose ≥ 1 year: 60mg/m2/dose ≥ 6 months and \< 1 year: 48 mg/m2/dose \< 6 months: 42mg/m2/dose
For patients with CNS 1 or CNS 2, on Days 1, 15, and 29
For patients with CNS 3, on Days 1, 8, 15, 22, and 29
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)
Eligibility Criteria
You may qualify if:
- Age Patients must be ≤21 years of age at the time of enrollment.
- Phase 1 - Initial enrollment will be restricted to patients \< 18 years of age until 9 such patients are enrolled
- Phase 2 - Initial enrollment will be restricted to patients \< 18 years of age until 6 such patients are enrolled (applies to Stratum A only)
- Diagnosis Patients must have a diagnosis of relapsed/refractory ALL or LLy with or without extramedullary disease (including CNS2 and CNS3). Patient with mixed phenotype ALL or mature B (Burkitt-like) leukemia are not eligible.
- Patients with ALL must have ≥ 5% blasts by morphology.
- Patients with LLy must have measurable disease documented by clinical, radiologic or histologic criteria
- Performance Level Karnofsky ≥ 50% for patients \> 16 years of age and Lansky ≥ 50% for patients ≤ 16 years of age.
- Prior Therapy A. Prior therapeutic attempts
- Phase 1 - Any patients with relapsed/refractory ALL or LLy
- Phase 2
- B-cell ALL/LLy: all patients must have failed two or more therapeutic attempts.
- T-cell ALL/LLy: all patients must have failed one or more therapeutic attempts. B. Recent prior chemotherapy Patients must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study.
- Myelosuppressive chemotherapy: At least 14 days must have elapsed since the completion of myelosuppressive therapy. However, patients may receive any of the following medications within 14 days without a "wash-out" period:
- Hydroxyurea: Hydroxyurea can be initiated and/or continued for up to 24 hours prior to the start of protocol therapy.
- "Maintenance-style" therapy - Therapy including vincristine (dosed at a maximum of one-time weekly), oral 6-mercaptopurine, oral methotrexate (dosed at a maximum of one-time weekly), dexamethasone (dosed at ≤ 3 mg\*/m\^2/dose twice daily), and prednisone (dosed at ≤ 20 mg\*/m\^2/dose twice daily) can be initiated and/or continued for up to 24 hours prior to the start of protocol therapy.
- +19 more criteria
You may not qualify if:
- Patients will be excluded if they have isolated CNS or testicular disease.
- Patients will be excluded if they have ≥ grade 2 peripheral sensory or motor neuropathy (defined by the Modified "Balis" Pediatric Scale of Pediatric Neuropathies) at the time of enrollment.
- Patients will be excluded if they have a known allergy or intolerance to any of the drugs used in the study - except for Pegaspargase for which asparaginase Erwinia chrysanthemi (recombinant)-rywn (Rylaze®) or (if available) crisantaspase (Erwinase®), may be substituted for allergy to Pegaspargase
- Patients will be excluded if they have a systemic fungal, bacterial, viral or other infection that is exhibiting ongoing signs/symptoms related to the infection without improvement despite appropriate antibiotics or other treatment. The patient needs to be off pressors and have negative blood cultures for 48 hours.
- Patients will be excluded if there is a plan to administer non-protocol chemotherapy, radiation therapy, or immunotherapy during the study period.
- Patients will be excluded if they have significant concurrent disease, illness, psychiatric disorder or social issue that would compromise patient safety or compliance with the protocol treatment or procedures, interfere with consent, study participation, follow up, or interpretation of study results.
- Patients with DNA fragility syndromes (such as Fanconi anemia, Bloom syndrome) are excluded.
- Patients will be excluded if they have had a lifetime exposure of ≥400 mg/m2 doxorubicin equivalents of anthracyclines (anthracycline equivalence to doxorubicin conversion see appendix iv) .
- Concomitant medications Investigational drugs: Patients currently receiving another investigational drug are not eligible.
- Anti-GVHD agents post transplant: patients who are receiving cyclosporine, tacrolimus or other agents to prevent graft-versus-host disease post hematopoetic stem cell transplant are not eligible.
- CYP3A4 agents: patients who are currently receiving drugs that are strong inducers of CYP3A4 are not eligible.
- Patients with Ph+ALL and Ph-like ALL who are currently receiving TKI therapy
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Therapeutic Advances in Childhood Leukemia Consortiumlead
- Takedacollaborator
- Children's Hospital Los Angelescollaborator
Study Sites (18)
Children's Hospital Los Angeles
Los Angeles, California, 90027, United States
Children's Hospital Orange County
Orange, California, 92868, United States
Children's National Medical Center
Washington D.C., District of Columbia, 20010, United States
University of Miami
Miami, Florida, 33136, United States
Children's Healthcare of Atlanta
Atlanta, Georgia, 30322, United States
C.S. Mott Children's Hospital
Ann Arbor, Michigan, 48109, United States
Children's Hospital and Clinics of Minnesota
Minneapolis, Minnesota, 55404, United States
Columbia University Medical Center
New York, New York, 10032, United States
Levine Cancer Institute
Charlotte, North Carolina, 28204, United States
University Hospitals Seidman Cancer Center
Cleveland, Ohio, 44106, United States
Nationwide Children's Hospital
Columbus, Ohio, 43205, United States
Doernbecher Children's Hospital
Portland, Oregon, 97239, United States
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104, United States
St. Jude Children's Research Hospital
Memphis, Tennessee, 38105, United States
University of Texas, Southwestern
Dallas, Texas, 75235, United States
Cook Children's Medical Center
Fort Worth, Texas, 76104, United States
Texas Children's Hospital/Baylor University
Houston, Texas, 77030, United States
The Children's Hospital at Westmead
Westmead, New South Wales, 2145, Australia
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- TACL
- Organization
- TACL
Study Officials
- STUDY CHAIR
Terzah Horton, MD
Baylor College of Medicine
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- GT60
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
January 22, 2019
First Posted
January 25, 2019
Study Start
February 12, 2019
Primary Completion
December 3, 2023
Study Completion
June 30, 2025
Last Updated
June 17, 2025
Results First Posted
June 17, 2025
Record last verified: 2025-05
Data Sharing
- IPD Sharing
- Will not share