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ALL, ChildhoodPhase 1/2NCT03817320

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

A Phase 1/2 study testing Ixazomib, Vincristine and Dexamethasone in people with ALL, Childhood and Lymphoblastic Lymphoma, Childhood, run by Therapeutic Advances in Childhood Leukemia Consortium at 18 sites in 2 countries.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
Search all trials

Trial 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). Read more about this study

Who is it for?
Ages 1 year to 21 years
What is being tested?
Ixazomib, Vincristine and Dexamethasone
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
24 participants
Where
18 sitesin 2 countries
Study dates
12 Feb 2019to 30 Jun 2025
Phase
Phase 1/2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 1 year to 21 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

Who may be able to join

  • 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
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  • 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.
  • Doses can be rounded to adjust for pill size
  • Hematopoietic stem cell transplant: Patients who have experienced their relapse after a HSCT are eligible, provided they have no evidence of acute or chronic Graft-versus-Host Disease (GVHD), are not receiving GVHD prophylaxis or treatment, and are at least 90 days post-transplant at the time of enrollment.
  • Hematopoietic growth factors: It must have been at least 7 days since the completion of therapy with G-CSF or other growth factors at the time of enrollment. It must have been at least 14 days since the completion of therapy with long-acting filgrastim (pegfilgrastim or biosimilar)
  • Biologic (anti-neoplastic agent): At least 7 days since the last dose of a biologic agent. For agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur. The duration of this interval must be discussed with the study chair
  • Monoclonal antibodies: At least 3 half-lives of the antibody or 21 days (whichever is shorter) must have elapsed after the last dose of monoclonal antibody. (i.e., blinatumomab half-life = 6 hours, therefore washout is 18 hours; inotuzumab half-life = 37 days therefore washout is 21 days; rituximab half-life = 66 days, therefore washout is 21 days). If steroids are being used to modify immune-related adverse events of antibody therapy, at least 14 days must have elapsed since the last dose of corticosteroid.
  • Immunotherapy: At least 30 days after the completion of any type of immunotherapy, e.g., tumor vaccines, CAR T cells. If steroids are being used to modify immune-related adverse events of immunotherapy, at least 14 days must have elapsed since the last dose of corticosteroid.
  • XRT: Craniospinal XRT is prohibited during protocol therapy. No washout period is necessary for radiation given to any extramedullary site other than CNS; ≥90 days must have elapsed if prior total body irradiation (TBI) or craniospinal XRT.
  • Anthracyclines: Patients must have had a lifetime exposure of <400 mg/m^2 of doxorubicin equivalents of anthracyclines.
  • Proteasome inhibitors: Patients with a prior exposure to proteasome inhibitors (e.g., bortezomib, carfilzomib) are eligible as long as the patient demonstrated at least a partial response to a proteasome inhibitor with chemotherapy combination. This criteria only applies to the Phase 2 portion of the study.
  • -Renal and hepatic function
  • Patients must have adequate renal and hepatic functions as indicated by the following laboratory values:
  • Adequate renal function defined as: Patient must have a calculated creatinine clearance or radioisotope GFR ≥ 70ml/min/1.73m^2 OR a normal serum creatinine based on age/gender
  • Adequate Liver Function Defined as: Direct bilirubin ≤ 1.5 x upper limit of normal (ULN) for age or normal (except in the presence of Gilbert's syndrome), AND alanine transaminase (ALT) ≤ 5 x ULN for age. The hepatic requirements are waived for patients with known or suspected liver involvement by leukemia or lymphoma. This must be reviewed by and approved by the study chair or vice chair.
  • Adequate Cardiac Function Defined as: Shortening fraction of ≥ 27% by echocardiogram, OR ejection fraction of ≥ 50% by radionuclide angiogram (MUGA).
  • Reproductive Function A. Female patients of childbearing potential must have a negative urine or serum pregnancy test confirmed within 2 weeks prior to enrollment.
  • Female patients with infants must agree not to breastfeed their infants while on this study.
  • Male and female patients of child-bearing potential must agree to use an effective method of contraception approved by the investigator during the study and for a minimum of 6 months after study treatment.
  • Informed Consent Patients and/or their parents or legal guardians must be capable of understanding the investigational nature, potential risks and benefits of the study. All patients and/or their parents or legal guardians must sign a written informed consent. Age appropriate assent will be obtained per institutional guidelines. To allow non-English speaking patients to participate in this study, bilingual health services will be provided in the appropriate language when feasible.
  • All institutional, FDA, and OHRP requirements for human studies must be met.

Who cannot join

  • 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.
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  • 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

Trial locations and contacts

18 sites in 2 countries.

18 sites in 2 countries

United States17 sites

  • C.S. Mott Children's Hospital

    Ann Arbor, Michigan, 48109

  • Children's Healthcare of Atlanta

    Atlanta, Georgia, 30322

  • Levine Cancer Institute

    Charlotte, North Carolina, 28204

  • University Hospitals Seidman Cancer Center

    Cleveland, Ohio, 44106

  • Nationwide Children's Hospital

    Columbus, Ohio, 43205

  • University of Texas, Southwestern

    Dallas, Texas, 75235

  • Cook Children's Medical Center

    Fort Worth, Texas, 76104

  • Texas Children's Hospital/Baylor University

    Houston, Texas, 77030

  • Children's Hospital Los Angeles

    Los Angeles, California, 90027

  • St. Jude Children's Research Hospital

    Memphis, Tennessee, 38105

  • University of Miami

    Miami, Florida, 33136

  • Children's Hospital and Clinics of Minnesota

    Minneapolis, Minnesota, 55404

  • Columbia University Medical Center

    New York, New York, 10032

  • Children's Hospital Orange County

    Orange, California, 92868

  • Children's Hospital of Philadelphia

    Philadelphia, Pennsylvania, 19104

  • Doernbecher Children's Hospital

    Portland, Oregon, 97239

  • Children's National Medical Center

    Washington D.C., District of Columbia, 20010

Other trials in United States

Australia1 site

  • The Children's Hospital at Westmead

    Westmead, New South Wales, 2145

Other trials in Australia

About this study

Official title: 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

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).

Read the 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.

Being tested
Ixazomib, Vincristine, Dexamethasone, Asparaginase, Doxorubicin
Medical subject headings
Precursor Cell Lymphoblastic Leukemia-Lymphoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • IxazomibDrug

    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

  • VincristineDrug

    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

  • DexamethasoneDrug

    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)

  • AsparaginaseDrug

    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

  • DoxorubicinDrug

    Day 1

    Dose ≥ 1 year: 60mg/m2/dose

    ≥ 6 months and < 1 year: 48 mg/m2/dose

    < 6 months: 42mg/m2/dose

  • Methotrexate (IT)Drug

    For patients with CNS 1 or CNS 2, on Days 1, 15, and 29

  • Triple IT (Methotrexate, Hydrocortisone, Cytarabine)Drug

    For patients with CNS 3, on Days 1, 8, 15, 22, and 29

  • LeucovorinDrug

    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)

Study groups in NCT03817320
Study groupRoleWhat they receive
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.
Receives: Drug: Ixazomib; Drug: Vincristine; Drug: Dexamethasone; Drug: Asparaginase; Drug: Doxorubicin; Drug: Methotrexate (IT); Drug: Triple IT (Methotrexate, Hydrocortisone, Cytarabine)
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.
Receives: Drug: Ixazomib; Drug: Vincristine; Drug: Dexamethasone; Drug: Asparaginase; Drug: Doxorubicin; Drug: Methotrexate (IT); Drug: Triple IT (Methotrexate, Hydrocortisone, Cytarabine)
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.
Receives: Drug: Ixazomib; Drug: Vincristine; Drug: Dexamethasone; Drug: Asparaginase; Drug: Doxorubicin; Drug: Methotrexate (IT); Drug: Triple IT (Methotrexate, Hydrocortisone, Cytarabine)
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).
Receives: Drug: Ixazomib; Drug: Vincristine; Drug: Dexamethasone; Drug: Asparaginase; Drug: Doxorubicin; Drug: Methotrexate (IT); Drug: Triple IT (Methotrexate, Hydrocortisone, Cytarabine); Drug: Leucovorin

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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

    Measured: 5 weeks

  2. 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).

    Measured: End of Block 1 treatment, Day 29-35 of treatment, assessed within 35 days from treatment start

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted25 Jan 2019
  2. Study start12 Feb 2019
  3. Primary completion3 Dec 2023
  4. Study completion30 Jun 2025 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
24 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03817320
Sponsor's protocol ID
T2017-002
Status last verified
May 2025
First submitted
22 Jan 2019
Last updated
17 Jun 2025
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • Schafer ES, Pacenta HL, Chi YY, Malvar J, Doan A, Schore RJ, Rushing T, Leong R, Bujarski S, Gaynon PS, Karol SE, Barredo JC, Rheingold SR, Huynh V, Gossai NP, Chang BH, Slone T, Pauly M, Wayne AS, Bhojwani D, Horton TM. Ixazomib with chemotherapy for childhood relapsed acute lymphoblastic leukemia: a TACL consortium report. Blood Neoplasia. 2026 May 16;3(3):100247. doi: 10.1016/j.bneo.2026.100247. eCollection 2026 Aug.

    PubMed 42376206

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Ixazomib, Vincristine and Dexamethasone in people with ALL, Childhood and Lymphoblastic Lymphoma, Childhood, run by Therapeutic Advances in Childhood Leukemia Consortium at 18 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 34 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 17 Jun 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 18 sites in United States, Australia. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 17 Jun 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Phase 1: Dose Limiting Toxicity (DLT) During Block 1 of Chemotherapy (time frame: 5 weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03817320, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Jun 2025.

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