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Active, Not Recruiting

NCT Number: NCT02553460

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

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:

* 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.

Active, Not Recruiting

This study is active but is not currently recruiting participants.

Key information

Conditions

Acute Lymphoblastic Leukemia Hematologic Diseases Hemic and Lymphatic Diseases Immune System Diseases Immunoproliferative Disorders Leukemia Leukemia, Lymphoid Lymphatic Diseases Lymphoproliferative Disorders Neoplasms Neoplasms by Histologic Type Precursor Cell Lymphoblastic Leukemia-Lymphoma

Age range

Up to 365 day

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1 / Phase 2

Primary location

Alberta Children's Hospital, Calgary, Alberta, Canada

Loading trial locations.

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • 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.

Exclusion criteria

  • 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.

Treatment and study plan

ITMHA

Drug

Given intrathecally (IT).

Other names: Intrathecal Triples, Methotrexate/hydrocortisone/cytarabine

Dexamethasone

Drug

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

Other names: Decadron®, Hexadrol®, Dexone®, Dexameth®

Mitoxantrone

Drug

Given IV.

Other names: Novantrone®, Mitozantrone

pegaspargase

Drug

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

Other names: PEG-asparaginase, Oncaspar®

Asparaginase Erwinia chrysanthemi

Drug

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

Other names: Erwinia chrysanthemi, Erwinase®, Erwinaze^T^M, Crisantaspase

bortezomib

Drug

Given IV.

Other names: Velcade®, PS-341, MLN341, LDP-341

Vorinostat

Drug

Taken PO or NG.

Other names: Solinza®, Suberoylanidide Hydroxamic Acid, SAHA

Cyclophosphamide

Drug

Given IV.

Other names: Cytoxan®

mercaptopurine

Drug

Given PO or NG.

Other names: 6-MP, Purinethol®

methotrexate

Drug

Given IV, IM or PO.

Other names: MTX, High Dose MTX

leucovorin calcium

Drug

Leucovorin rescue PO or IV.

Other names: Wellcovorin®, Folinic acid

Cytarabine

Drug

Given IV.

Other names: Ara-C, Cytosar-U®

etoposide

Drug

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

Other names: VP-16, Vepesid®

Vincristine

Drug

Given IV.

Other names: Oncovin®

Primary outcomes

  1. Percentage of Treatment-related Mortality (TRM)

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

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

    Presented as percentage

Secondary outcomes

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

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

    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.

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

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

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

  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.

    Time frame: 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)

    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.

Sponsors and collaborators

Lead sponsor

St. Jude Children's Research Hospital

Other

Collaborators

  • Baylor College of Medicine
  • Gateway for Cancer Research

Registry information

Important dates

Study start
2016
Primary completion
2022
Study completion
2031
First posted
Sep 17, 2015
Registry last updated
Jun 24, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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