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TOT17: Total Therapy for Children with Acute Lymphoblastic Leukemia and Lymphoma

Total Therapy Study 17 for Newly Diagnosed Patients with Acute Lymphoblastic Leukemia and Lymphoma


Leukemia / Lymphoma

Psychology and Biobehavioral Medicine

Diseases Treated:

Leukemia and lymphoma

Eligibility Overview:

  • Diagnosis of B-cell or T-cell acute lymphoblastic leukemia (ALL) or acute lymphoblastic lymphoma (LLy)
  • 1 to 18 years old
  • No prior therapy or limited prior therapy
  1. Brief Summary

    Survival in pediatric acute lymphoblastic leukemia (ALL) has improved to more than 90% in recent clinical trials. Further progress requires early identification of leukemia subtypes for risk-directed treatment to avoid over- or under-treatment. The TOT17 protocol applies the most comprehensive risk classification to date, combining blast cell immunophenotype and leukemia-specific genomic features with presenting clinical characteristics and early treatment minimal residual disease (MRD) response in order to maximize leukemia control while reducing adverse effects.

    In this study, patients will be divided into three risk groups: low-, standard- and high-risk. Treatment will consist of three main phases: remission induction, consolidation and continuation.

    The TOT17 protocol incorporates multiple complementary innovative therapeutic, quality-of-life, genomic, biologic and pharmacologic objectives to address important questions across the spectrum of risk groups and molecular subtypes of childhood ALL/LLy. These studies will generate new biological and therapeutic insights that will advance precision medicine strategies to push cure rates closer to 100% while improving the quality of life for children with ALL and LLy.

    Primary Objectives

    • To improve the event-free survival of provisional standard- or high-risk patients with genetically or immunologically targetable lesions or minimal residual disease (MRD) ≥ 5% at Day 15 or ≥1% at the end of Remission Induction, by the addition of molecular and immunotherapeutic approaches including tyrosine kinase inhibitors or blinatumomab for refractory B-ALL, and the proteasome inhibitor or chimeric antigen receptor (CAR) T cells/bortezomib for those lacking targetable lesions
    • To improve overall treatment outcome of T-ALL by optimizing pegaspargase and cyclophosphamide treatment and by the addition of new agents in patients with targetable genomic abnormalities (e.g., activated tyrosine kinases or JAK/STAT mutations) or by the addition of bortezomib for those who have a poor early response to treatment but no targetable lesions, and by administering nelarabine to T-ALL patients with leukemia cells in cerebrospinal fluid at diagnosis or MRD ≥0.01% at the end of induction
    • To examine in a randomized study design whether the administration of two doses of rituximab to children with B-ALL during early Remission Induction therapy decreases allergic reactions to pegaspargase
    • To determine in a randomized study design whether the incidence and/or severity of acute vincristine-induced peripheral neuropathy can be reduced by decreasing the dosage of vincristine in patients with the high-risk CEP72 TT genotype or by shortening the duration of vincristine therapy in patients with the CEP72 CC or CT genotype

    Eligibility Criteria

    Inclusion criteria include:

    • Diagnosis of B-cell or T-cell acute lymphoblastic leukemia (ALL) or acute lymphoblastic lymphoma (LLy)
    • 1 to 18 years old
    • No prior therapy or limited prior therapy

    Exclusion Criteria include:

    • Pregnant or breastfeeding

    Study Sites

    St. Jude Children’s Research Hospital, Memphis, Tennessee
    Collaborating sites in and outside the U.S.

  2. About this study

    Acute lymphoblastic leukemia and acute lymphoblastic lymphoma are cancers of blood cells. They are often known simply as ALL and LLy. These cancers are alike in many ways.  Their treatments are also similar.

    Both ALL and LLy grow quickly and need to be treated immediately with a combination of anti-cancer drugs, known as chemotherapy. Previous studies have shown that most children with ALL can have a long-term remission if they get strong chemotherapy with several drugs.

    In this study, children will be assigned to receive a specific treatment based on their level of risk and disease cell type. Risk refers to the chance of the disease coming back after therapy. Cell type refers to the type of white blood cell that is affected: B-cell or T-cell.

    Some study participants with B-cell ALL and LLy may be eligible for a type of immunotherapy called CAR T-Cell Therapy. This treatment is designed to help the body recognize and fight diseases. Other patients in the study may be given blinatumomab, an immunotherapy drug. The U.S. Food and Drug Administration (FDA) has approved this drug to treat adults and children with ALL that has not responded to treatment (refractory) or has come back after treatment (relapsed). The FDA has not approved blinatumomab for patients with newly diagnosed ALL or LLy.

    Patients in this clinical trial will be treated in three stages over approximately 2½ years:

    1. Remission induction – Doctors try to remove all visible signs of disease and allow normal blood cells to be restored.
    2. Consolidation – Doctors try to deliver a “knock-out punch” to any remaining disease cells.
    3. Continuation – Doctors try to keep the disease from coming back.

    Purpose of this clinical trial

    The main goal of this study is to try and improve the cure rate and quality of life of children, adolescents and young adults with acute lymphoblastic leukemia and lymphoma, by adding “targeted” treatments that are tailored to each child’s specific type of ALL or LLy.

    Eligibility overview

    • Diagnosis of B-cell or T-cell acute lymphoblastic leukemia (ALL) or acute lymphoblastic lymphoma (LLy)
    • 1 to 18 years old
    • No prior therapy or limited prior therapy
  3. TOT17 Quick View
    Sponsors St. Jude Children’s Research Hospital identifier NCT03117751
    Trial Start Date March 2017
    Estimated Enrollment 1,00
    Study Type Interventional
    Study Phase Phase III
    Conditions Leukemia / Lymphoma
    Ages 1 to 18 years old
    St. Jude Principal investigator Hiroto Inaba, MD, PhD
    Study Sites St. Jude Children’s Research Hospital and collaborating sites in and outside the U.S.
    For a consultation or to discuss TOT17
    St. Jude Physician/Patient Referral Office

St. Jude Children’s Research Hospital
262 Danny Thomas Place
Memphis, TN 38105  USA
Voice: 1-888-226-4343 or 901-595-4055
24-Hour Emergency Access Pager: 1-800-349-4334

The above information is intended to provide only a basic description about a research protocol that may be currently active at St. Jude. The details made available here may not be the most up-to-date information on protocols used by St. Jude. To receive full details about a protocol and its status and or use at St. Jude, a physician must contact St. Jude directly.