AzTrials
AzTrials

Acute Lymphoblastic LeukemiaPhase 1/2NCT02553460

Total Therapy for Infants With Acute Lymphoblastic Leukemia (ALL) I

A Phase 1/2 study testing ITMHA, Dexamethasone and Mitoxantrone in people with Acute Lymphoblastic Leukemia, run by St. Jude Children's Research Hospital at 15 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

The purpose of this study is to test the good and bad effects of the study drugs bortezomib and vorinostat when they are given in combination with chemotherapy commonly used to treat acute lymphoblastic leukemia (ALL) in infants. Read more about this study

Who is it for?
Ages Up to 365 days
Conditions the study is for
Acute Lymphoblastic Leukemia
What is being tested?
ITMHA, Dexamethasone and Mitoxantrone
Could I receive a placebo?
No, everyone receives an active treatment
How many people
50 participants
Where
15 sitesin 2 countries
Study dates
29 Jan 2016to Oct 2031
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 Up to 365 days
  • All sexes
  • No healthy volunteers
  • Child

Who may be able to join

  • Patient is ≤ 365 days of age at the time of diagnosis.
  • Patient has newly diagnosed acute lymphoblastic leukemia (ALL) or acute undifferentiated leukemia with ≥25% blasts in the bone marrow (M3), with or without extramedullary disease. Patients with T-cell ALL are eligible. Patients with bilineage or biphenotypic acute leukemia are eligible, provided the morphology and immunophenotype are predominantly lymphoid.
  • Limited prior therapy, including hydroxyurea for 72 hours or less, systemic glucocorticoids for one week or less, one dose of vincristine, and one dose of intrathecal chemotherapy.
  • Written informed consent following Institutional Review Board, NCI, FDA, and Office for Human Research Protections (OHRP) Guidelines.

Who cannot join

  • Patients with prior therapy, other than therapy specified in the Inclusion Criteria.
  • Patients with mature B-cell ALL or acute myelogenous (AML).
  • Patients with Down syndrome.
  • Inability or unwillingness of legal guardian/representative to give written informed consent.

Trial locations and contacts

15 sites in 2 countries.

15 sites in 2 countries

United States9 sites

  • St. Jude Affiliate-Charlotte

    Charlotte, North Carolina, 28204

  • Cincinnati Children's Hospital

    Cincinnati, Ohio, 45229

  • Children's Hospital Los Angeles

    Los Angeles, California, 90027

  • St. Jude Children's Research Hospital

    Memphis, Tennessee, 38105

  • Children's Hospital and Clinics of Minnesota

    Minneapolis, Minnesota, 55404

  • Children's Hospital of the King's Daughters (CHKD)

    Norfolk, Virginia, 23507

  • Children's Hospital of Orange County

    Orange, California, 92868

  • Lucile Packard Children's Hospital Stanford University

    Palo Alto, California, 94304

  • Oregon Health and Science University

    Portland, Oregon, 97239

Other trials in United States

Canada6 sites

  • Alberta Children's Hospital

    Calgary, Alberta, T3A 6A8

  • Stollery Children's Hospital

    Edmonton, Alberta, T6G 2B7

  • Centre Hospitalier Universitaire Sainte-Justine

    Montreal, Quebec, H3T 1C5 CAN

  • The Montreal Children's Hospital (MUHC-McGill)

    Montreal, Quebec, H4A 3J1

  • Centre Hospitalier Universitaire de Quebec

    Québec, Quebec, G1V 4G2

  • Children's & Women's Health Centre of British Columbia

    Vancouver, British Columbia, V6H 3V4

Other trials in Canada

About this study

The purpose of this study is to test the good and bad effects of the study drugs bortezomib and vorinostat when they are given in combination with chemotherapy commonly used to treat acute lymphoblastic leukemia (ALL) in infants. For example, adding these drugs could decrease the number of leukemia cells, but it could also cause additional side effects. Bortezomib and vorinostat have been approved by the US Food and Drug Administration (FDA) to treat other cancers in adults, but they have not been approved for treating children with leukemia. With this research, we plan to meet the following goals:

PRIMARY OBJECTIVE:

Read more
  • Determine the tolerability of incorporating bortezomib and vorinostat into an ALL chemotherapy backbone for newly diagnosed infants with ALL.

SECONDARY OBJECTIVES:

  • Estimate the event-free survival and overall survival of infants with ALL who are treated with bortezomib and vorinostat in combination with an ALL chemotherapy backbone.
  • Measure minimal residual disease (MRD) positivity using both flow cytometry and PCR.
  • Compare end of induction, end of consolidation, and end of reinduction MRD levels to Interfant99 (ClinicalTrials.gov registration ID number NCT00015873) participant outcomes.
Read the detailed description

Treatment will consist of 4 main phases: Remission Induction, Consolidation, Reinduction, and Maintenance. High risk patients will receive a reintensification phase prior to transplant in first remission.

REMISSION INDUCTION: Chemotherapy will be given in an attempt to induce the participant's leukemia into remission. Drugs given are intrathecal triple drug treatment with methotrexate, hydrocortisone and Ara-C (ITMHA); dexamethasone; vorinostat; bortezomib; PEG-asparaginase; mitoxantrone; cyclophosphamide; cytarabine; and 6-mercaptopurine.

CONSOLIDATION PHASE: After the participant's blood counts have recovered from Remission Induction, he/she will move to the consolidation phase. This therapy is given to kill any remaining leukemia cells. Drugs given are ITMHA, high-dose methotrexate, and 6-mercaptopurine.

RE-INDUCTION: This phase aims to improve the participant's overall response to therapy by again seeking to bring his/her leukemia into remission. Drugs given are ITMHA, mitoxantrone, peg-asparaginase, dexamethasone, bortezomib, and vorinostat.Participants that achieve MRD negative status following Re-Induction may proceed directly to stem cell transplant (SCT) (SCT not part of this study).

RE-INTENSIFICATION: Participants that remain MRD positive following Consolidation or Reinduction may receive Chimeric Antigen Receptor T-Cell therapy (CART), if available (CART is not part of this study), or proceed to a Reintensification phase then go on to stem cell transplant (SCT).

MAINTENANCE PHASE: Participants with negative MRD after consolidation will skip the re-intensification phase and proceed to receive maintenance therapy to keep the leukemia from returning. Drugs given are ITMHA, dexamethasone, vincristine, 6-mercaptopurine and methotrexate. Each cycle of these drugs lasts 28 days and will be repeated up to 20 times as long as there are no serious side effects.

Being tested
ITMHA, Dexamethasone, Mitoxantrone, Pegaspargase, Asparaginase Erwinia Chrysanthemi
Keywords
Infants
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.

  • ITMHADrug

    Also called Intrathecal Triples, Methotrexate/hydrocortisone/cytarabine

    Given intrathecally (IT).

  • DexamethasoneDrug

    Also called Decadron®, Hexadrol®, Dexone®, Dexameth®

    Given orally (PO) or naso-gastrically (NG) or intravenously (IV).

  • MitoxantroneDrug

    Also called Novantrone®, Mitozantrone

    Given IV.

  • PegaspargaseDrug

    Also called PEG-asparaginase, Oncaspar®

    Given IV. If participant is allergic to pegaspargase, Asparaginase Erwinia Chrysanthemi will be used.

  • Asparaginase Erwinia ChrysanthemiDrug

    Also called Erwinia chrysanthemi, Erwinase®, Erwinaze^T^M, Crisantaspase

    Asparaginase Erwinia Chrysanthemi will be used in case of allergy or intolerance of participant to PEG-asparaginase. Given IV (preferred) or intramuscularly (IM).

  • BortezomibDrug

    Also called Velcade®, PS-341, MLN341, LDP-341

    Given IV.

  • VorinostatDrug

    Also called Solinza®, Suberoylanidide Hydroxamic Acid, SAHA

    Taken PO or NG.

  • CyclophosphamideDrug

    Also called Cytoxan®

    Given IV.

  • MercaptopurineDrug

    Also called 6-MP, Purinethol®

    Given PO or NG.

  • MethotrexateDrug

    Also called MTX, High Dose MTX

    Given IV, IM or PO.

  • Leucovorin CalciumDrug

    Also called Wellcovorin®, Folinic acid

    Leucovorin rescue PO or IV.

  • CytarabineDrug

    Also called Ara-C, Cytosar-U®

    Given IV.

  • EtoposideDrug

    Also called VP-16, Vepesid®

    Given IV. In case of participant allergy, etoposide phosphate (Etopophos®) will be given.

  • VincristineDrug

    Also called Oncovin®

    Given IV.

Study groups in NCT02553460
Study groupRoleWhat they receive
TreatmentExperimentalParticipants who meet eligibility requirements will receive remission induction, consolidation treatment, reinduction, reintensification and maintenance therapy. Interventions: ITMHA, dexamethasone, mitoxantrone, pegaspargase or asparaginase Erwinia chrysanthemi, bortezomib, vorinostat, cyclophosphamide, mercaptopurine, methotrexate, leucovorin calcium, cytarabine, etoposide, and vincristine.
Receives: Drug: ITMHA; Drug: Dexamethasone; Drug: Mitoxantrone; Drug: Pegaspargase; Drug: Asparaginase Erwinia Chrysanthemi; Drug: Bortezomib; Drug: Vorinostat; Drug: Cyclophosphamide; Drug: Mercaptopurine; Drug: Methotrexate; Drug: Leucovorin Calcium; Drug: Cytarabine; Drug: Etoposide; Drug: Vincristine

What is being measured

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

  1. Percentage of Treatment-related Mortality (TRM)

    Number of treatment related deaths divided by total number of patients during induction or reinduction therapy.

    Presented as percentage

    Measured: At the end of reinduction (up to 5 months after start of therapy)

Secondary outcomes (3)

  1. Percentage of Participants With 3-year Event Free Survival (EFS)

    Event-free survival (EFS) will be estimated by the Kaplan-Meier estimator. For EFS, relapse and second malignancies will be considered as failures in addition to death in complete remission. The time to EFS will be set to 0 for patients who fail to achieve complete remission. EFS probability will be estimated with 95% confidence intervals.

    Measured: 3 years after completion of therapy (up to 5 years after start of therapy)

  2. Percentage of Participants With 5-year Overall Survival (OS)

    Overall survival (OS) will be estimated by the Kaplan-Meier estimator with 95% confidence intervals.

    Measured: 5 years after completion of therapy (up to 7 years after start of therapy)

  3. Minimal Residual Disease (MRD) Positivity Using Flow Cytometry or PCR at Induction Day 22, End of Induction, End of Consolidation, and End of Maintenance.

    Proportion of participants with positive MRD at the end of each therapy block. The proportion of MRD positive patients is determined by the number of patients that are MRD positive at the end of each therapy block divided by the number of patients that completed each therapy block.

    Measured: At the end of induction day 22 (approximately 3 weeks), end of induction (approximately 6 weeks), end of consolidation (approximately 14 weeks), and end of maintenance therapy (approximately 2 years)

Timeline

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

  1. First posted17 Sep 2015 (estimated)
  2. Study start29 Jan 2016
  3. Primary completion10 May 2022
  4. Study completionOct 2031 (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
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
50 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02553460
Sponsor's protocol ID
TINI
Other IDs
NCI-2015-01493
Status last verified
Jun 2026
First submitted
16 Sep 2015
Last updated
24 Jun 2026
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • Gruber TA, Jeha S, Deyell RJ, Lewis V, Chang BH, Lowe EJ, Frediani J, Vezina C, Michon B, Richards M, Breese EH, Tran TH, Lacayo N, Bolen C, Desai S, Pauley JL, Huang M, Ashcraft E, Cheng C, Schultz KR, Stork L, Schlis K, Huynh VT, Gossai N, Messinger YH, Bittencourt H, Horton TM, Athale U, Stearns D, Schiff D, Gaynon PS. Bortezomib and vorinostat in combination with mitoxantrone, dexamethasone, and pegasparaginase during induction and reinduction for infants with acute lymphoblastic leukaemia: a multicentre single-arm phase 1/2 study. Lancet Haematol. 2026 Mar;13(3):e144-e156. doi: 10.1016/S2352-3026(25)00357-6. Epub 2026 Feb 12.

    PubMed 41692013

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing ITMHA, Dexamethasone and Mitoxantrone in people with Acute Lymphoblastic Leukemia, run by St. Jude Children's Research Hospital at 15 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 4 inclusion and 4 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 24 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 15 sites in United States, Canada. 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 7 Jun 2023). 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?

Percentage of Treatment-related Mortality (TRM) (time frame: At the end of reinduction (up to 5 months after start of therapy)). 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 NCT02553460, 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 24 Jun 2026.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in