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

NCT02553460 | Active Not Recruiting Phase 1 Results DMC FDA Drug

• 2 other identifiers: TININCI-2015-01493
• Study Type: interventional
• Target: 50
• Locations: 2 countries
• Sites: 15

Brief 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. 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.

Conditions

Acute Lymphoblastic Leukemia

Keywords

Infants

Outcome Measures

Primary Outcomes (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

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

Secondary Outcomes (3)

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

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

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

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

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

  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)

Study Arms (1)

Treatment

EXPERIMENTAL

Participants 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.

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

Interventions

ITMHA DRUG

Given intrathecally (IT).

Also known as: Intrathecal Triples, Methotrexate/hydrocortisone/cytarabine

Treatment

Dexamethasone DRUG

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

Also known as: Decadron®, Hexadrol®, Dexone®, Dexameth®

Treatment

Mitoxantrone DRUG

Given IV.

Also known as: Novantrone®, Mitozantrone

Treatment

Pegaspargase DRUG

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

Also known as: PEG-asparaginase, Oncaspar®

Treatment

Bortezomib DRUG

Given IV.

Also known as: Velcade®, PS-341, MLN341, LDP-341

Treatment

Vorinostat DRUG

Taken PO or NG.

Also known as: Solinza®, Suberoylanidide Hydroxamic Acid, SAHA

Treatment

Cyclophosphamide DRUG

Given IV.

Also known as: Cytoxan®

Treatment

Mercaptopurine DRUG

Given PO or NG.

Also known as: 6-MP, Purinethol®

Treatment

Methotrexate DRUG

Given IV, IM or PO.

Also known as: MTX, High Dose MTX

Treatment

Leucovorin Calcium DRUG

Leucovorin rescue PO or IV.

Also known as: Wellcovorin®, Folinic acid

Treatment

Cytarabine DRUG

Given IV.

Also known as: Ara-C, Cytosar-U®

Treatment

Etoposide DRUG

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

Also known as: VP-16, Vepesid®

Treatment

Vincristine DRUG

Given IV.

Also known as: Oncovin®

Treatment

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).

Also known as: Erwinia chrysanthemi, Erwinase®, Erwinaze^T^M, Crisantaspase

Treatment

Eligibility Criteria

• Age: Up to 365 Days
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• St. Jude Children's Research Hospital: lead
• Gateway for Cancer Research: collaborator
• Baylor College of Medicine: collaborator

Study Sites (15)

Children's Hospital Los Angeles

Los Angeles, California, 90027, United States

Location

Children's Hospital of Orange County

Orange, California, 92868, United States

Location

Lucile Packard Children's Hospital Stanford University

Palo Alto, California, 94304, United States

Location

Children's Hospital and Clinics of Minnesota

Minneapolis, Minnesota, 55404, United States

Location

St. Jude Affiliate-Charlotte

Charlotte, North Carolina, 28204, United States

Location

Cincinnati Children's Hospital

Cincinnati, Ohio, 45229, United States

Location

Oregon Health and Science University

Portland, Oregon, 97239, United States

Location

St. Jude Children's Research Hospital

Memphis, Tennessee, 38105, United States

Location

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

Norfolk, Virginia, 23507, United States

Location

Alberta Children's Hospital

Calgary, Alberta, T3A 6A8, Canada

Location

Stollery Children's Hospital

Edmonton, Alberta, T6G 2B7, Canada

Location

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

Vancouver, British Columbia, V6H 3V4, Canada

Location

Centre Hospitalier Universitaire Sainte-Justine

Montreal, Quebec, H3T 1C5 CAN, Canada

Location

The Montreal Children's Hospital (MUHC-McGill)

Montreal, Quebec, H4A 3J1, Canada

Location

Centre Hospitalier Universitaire de Quebec

Québec, Quebec, G1V 4G2, Canada

Location

Related Publications (1)

• 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.

  PMID: 41692013 DERIVED

Related Links

• St. Jude Children's Research Hospital
• Clinical Trials Open at St. Jude

MeSH Terms

Conditions

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Interventions

Methotrexate; Dexamethasone; Calcium Dobesilate; Mitoxantrone; pegaspargase; asparaginase erwinia chrysanthemi recombinant; Asparaginase; Bortezomib; Vorinostat; Cyclophosphamide; Mercaptopurine; Leucovorin; Cytarabine; Etoposide; Vincristine

Condition Hierarchy (Ancestors)

Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Benzenesulfonates; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Arylsulfonates; Arylsulfonic Acids; Sulfonic Acids; Sulfur Acids; Sulfur Compounds; Anthraquinones; Anthrones; Anthracenes; Polycyclic Aromatic Hydrocarbons; Quinones; Amidohydrolases; Hydrolases; Enzymes; Enzymes and Coenzymes; Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Pyrazines; Heterocyclic Compounds, 1-Ring; Anilides; Amides; Aniline Compounds; Amines; Hydroxamic Acids; Hydroxylamines; Hydroxy Acids; Carboxylic Acids; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Sulfhydryl Compounds; Purines; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Coenzymes; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Glucosides; Glycosides; Carbohydrates; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Indoles; Indolizidines; Indolizines

Results Point of Contact

• Title: Tanja A. Gruber, MD, PhD
• Organization: Lucile Packard Children's Hospital

tagruber@stanford.edu

(650) 723-5535

Study Officials

• Tanja Gruber, MD, PhD

  Lucile Packard Children's Hospital Stanford University

  STUDY CHAIR

• Sima Jeha, MD

  St. Jude Children's Research Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 16, 2015
• First Posted: September 17, 2015
• Study Start: January 29, 2016
• Primary Completion: May 10, 2022
• Study Completion (Estimated): October 1, 2031
• Last Updated: December 10, 2025
• Results First Posted: June 7, 2023

Record last verified: 2025-12

Locations

US (9); CA (6)