Total Therapy XVII for Newly Diagnosed Patients With Acute Lymphoblastic Leukemia and Lymphoma

NCT03117751 | Active Not Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: TOT17NCI-2017-00582
• Study Type: interventional
• Target: 790
• Locations: 2 countries
• Sites: 8

Brief Summary

The overarching objective of this study is to use novel precision medicine strategies based on inherited and acquired leukemia-specific genomic features and targeted treatment approaches to improve the cure rate and quality of life of children with acute lymphoblastic leukemia (ALL) and acute lymphoblastic lymphoma (LLy). Primary Therapeutic 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 Day 22 or ≥1% at the end of Remission Induction, by the addition of molecular and immunotherapeutic approaches including tyrosine kinase inhibitors or chimeric antigen receptor (CAR) T cell / blinatumomab for refractory B-acute lymphoblastic leukemia (B-ALL) or B-lymphoblastic lymphoma (B-LLy), and the proteasome inhibitor bortezomib for those lacking targetable lesions.
• To improve overall treatment outcome of T acute lymphoblastic leukemia (T-ALL) and T-lymphoblastic lymphoma (T-LLy) 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 and T-LLy patients with leukemia/lymphoma cells in cerebrospinal fluid at diagnosis or MRD ≥0.01% at the end of induction.
• 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 standard/high-risk patients with the CEP72 CC or CT genotype. Secondary Therapeutic Objectives:
• To estimate the event-free survival and overall survival of children with ALL and to assess the non-inferiority of TOTXVII compared to the historical control given by TOTXVI.
• To estimate the event-free survival and overall survival of children with LLy when ALL diagnostic and treatment approaches are used.
• To evaluate the efficacy of blinatumomab in B-ALL patients with end of induction MRD ≥0.01% to \<1% and those (regardless of MRD level or TOTXVII risk category) with the genetic subtypes of BCR-ABL1, ABL-class fusion, JAK-STAT activating mutation, hypodiploid, iAMP21, ETV6-RUNX1-like, MEF2D, TCF3-HLF, or BCL2/MYC or with Down syndrome, by comparing event-free survival to historical control from TOTXVI.
• To determine the tolerability of combination therapy with ruxolitinib and Early Intensification therapy in patients with activation of JAK-STAT signaling that can be inhibited by ruxolitinib and Day 15 or Day 22 MRD ≥5%, Day 42 MRD ≥1%, or LLy patients without complete response at the End of Induction and all patients with early T cell precursor leukemia. Biological Objectives:
• To use data from clinical genomic sequencing of diagnosis, germline/remission and MRD samples to guide therapy, including incorporation of targeted agents and institution of genetic counseling and cancer surveillance.
• To evaluate and implement deoxyribonucleic acid (DNA) and ribonucleic acid (RNA) sequencing-based methods to monitor levels of MRD in bone marrow, blood, and cerebrospinal fluid.
• To assess clonal diversity and evolution of pre-leukemic and leukemic populations using DNA variant detection and single-cell genomic analyses in a non-clinical, research setting.
• To identify germline or somatic genomic variants associated with drug resistance of ALL cells to conventional and newer targeted anti-leukemic agents in a non-clinical, research setting.
• To compare drug sensitivity of ALL cells from diagnosis to relapse in vitro and in vivo and determine if acquired resistance to specific agents is related to specific somatic genome variants that are not detected or found in only a minor clone at initial diagnosis. Supportive Care Objectives
• To conduct serial neurocognitive monitoring of patients to investigate the neurocognitive trajectory, mechanisms, and risk factors.
• To evaluate the impact of low-magnitude high frequency mechanical stimulation on bone mineral density and markers of bone turnover. There are several Exploratory Objectives.

Conditions

Acute Lymphoblastic Leukemia; Acute Lymphoblastic Lymphoma

Keywords

Leukemia; Lymphoma; Pediatric; B-Cell; T-Cell

Outcome Measures

Primary Outcomes (3)

• Event-free survival of ALL patients (EFS)

  5-year EFS: Kaplan-Meier estimates of EFS curve of ALL patients will be computed and compared historically with those of the St. Jude Children's Research Hospital's (SJCRH) TOTXVI study (NCT00549848). All eligible patients entered on the current TOT17 study will be included in these comparisons. Comparisons by log-rank tests will be made both un-stratified and stratified by risk groups.

  At 3.5 years after enrollment of the last participant

• Proportion of patients with CEP72TT genotype who develop two or more episodes of Grade 2 or higher neuropathy during Continuation

  This will be a single-blind, stratified block randomized experiment. Although the investigators who evaluate neuropathy and neuropathic pain and the patients are blinded for treatment assignment, treating clinicians and pharmacy staff are not. Patients will be randomized at a 1:1 ratio into two treatment groups: 1.5 mg/m\^2 vs. 1 mg/m\^2 vincristine (VCR) dose. Randomization will be stratified by two factors known to significantly affect neuropathy during the Continuation phase, namely, Grade 2 or higher neuropathy prior to Continuation (none, 1 episode, 2 or more episodes) and race (black, others). The proportion of patients who develop two or more episodes of Grade 2 or higher neuropathy during Continuation Treatment will be compared between the two VCR dose groups, using a Z-test for two sample proportions.

  At 6 months after the last randomized patient completes Continuation Treatment (Week 120).

• Cumulative incidence of Grade 2 or higher neuropathy in patients with CEP72 CC or CT genotype

  This will be a single blind stratified block randomized experiment. The investigators who evaluate neuropathy and neuropathic pain and the patients are blinded for treatment assignment. Treating clinicians and pharmacy staff will not be blinded. Standard/high-risk patients will be randomized at a 1:1 ratio into two treatment groups at Week 49 of Continuation therapy: to vincristine + dexamethasone (VCR+DEX) pulses or to 6-mercaptopurine + methotrexate (6MP+MTX). The primary analysis will compare the cumulative incidence of the first episode of Grade 2 or higher neuropathy or neuropathic pain (the end point) by stratified Gray's test. Adverse events other than the endpoint rendering a patient drop out after Continuation Week 49 are regarded as competing events.

  After the last randomized patient is followed for 1 year after Week 101 of Continuation therapy

Secondary Outcomes (13)

• 5-year overall survival (OS) of ALL patients compared to historical controls

  3.5 years after enrollment of the last patient

• EFS of LLy patients

  3.5 years after enrollment of the last patient

• 5-year OS of LLy patients

  3.5 years after enrollment of the last patient

• The efficacy of blinatumomab in B-ALL patients

  3.5 years after enrollment of the last patient

• Comparison of MRD measurements between flow cytometry and sequencing

  From Day 8 through Day 42 after remission induction (At 6 months after enrollment of the 40^t^h evaluable patient)

Other Outcomes (7)

• Log odds ratio of pharmacogenetic predictors of treatment outcome (host toxicity or in vivo efficacy)

  5 years after enrollment of the last participant

• Log odds ratio of pharmacokinetic predictors of treatment outcome (host toxicity or in vivo efficacy)

  5 years after enrollment of the last participant

• Log odds ratio of pharmacodynamic predictors of treatment outcome (host toxicity or in vivo efficacy)

  5 years after enrollment of the last participant

Study Arms (7)

B-ALL and B-LLy, Low-risk

EXPERIMENTAL

Patients with low-risk B ALL and LLy will have Induction (6 weeks), Consolidation (8 weeks), and Continuation (120 weeks). During Remission Induction therapy, prednisone dose is 40mg/m\^2 and 1-2 doses of daunorubicin (based on day 8 peripheral blood MRD in patients with ETV6-RUNX1 or hyperdiploid) are given. Dasatinib is given for patients with ABL-class fusion. Blinatumomab will be given to patients with certain genetic subtypes and those with Down syndrome. Interventions: Prednisone, vincristine, daunorubicin, pegaspargase (or Erwinase®, Rylaze™ or Calaspargase pegol), cyclophosphamide, cytarabine, mercaptopurine, dasatinib, thioguanine, methotrexate, dexamethasone, blinatumomab.

Drug: Prednisone; Drug: Vincristine; Drug: Daunorubicin; Drug: Pegaspargase; Drug: Erwinase®; Drug: Cyclophosphamide; Drug: Cytarabine; Drug: Mercaptopurine; Drug: Dasatinib; Drug: Methotrexate; Drug: Blinatumomab; Drug: Dexamethasone; Drug: Thioguanine; Drug: Asparaginase Erwinia chrysanthemi (recombinant)-rywn; Drug: Calaspargase Pegol

B-ALL and B-LLy, Standard-risk

EXPERIMENTAL

Induction (6wks), Early Intensification (4wks), Consolidation (8wks) and Continuation (120 wks). Remission Induction: Prednisone dose is 40mg/m\^2 and 2 doses daunorubicin are given. Dasatinib: given for patients with Ph+ and those with ABL-class fusion. Ruxolitinib: given for patients with activation of JAK-STAT signaling; ALL patients with Day 15 or Day 22 MRD ≥5%, LLy patients who don't qualify for complete response at end of Remission Induction and all patients with ETP and T/M MPAL. Bortezomib is given to patients without targetable lesions and Day 15 or Day 22 MRD \>5%. Blinatumomab will be given to patients with residual disease at the end of induction (≥0.01% and \<1%), certain genetic subtypes and Down syndrome. Interventions: prednisone, vincristine, daunorubicin, pegaspargase (or Erwinase®, Rylaze™ or Calaspargase pegol), cyclophosphamide, cytarabine, mercaptopurine, dasatinib, bortezomib, ruxolitinib, blinatumomab, thioguanine, methotrexate, dexamethasone, doxorubicin

Drug: Prednisone; Drug: Vincristine; Drug: Daunorubicin; Drug: Pegaspargase; Drug: Erwinase®; Drug: Cyclophosphamide; Drug: Cytarabine; Drug: Mercaptopurine; Drug: Dasatinib; Drug: Methotrexate; Drug: Blinatumomab; Drug: Ruxolitinib; Drug: Bortezomib; Drug: Dexamethasone; Drug: Doxorubicin; Drug: Thioguanine; Drug: Asparaginase Erwinia chrysanthemi (recombinant)-rywn; Drug: Calaspargase Pegol

B-ALL and B-LLy, High-risk

EXPERIMENTAL

Induction (6 weeks), Early Intensification (4 weeks), Consolidation (8 weeks), and Immunotherapy (chimeric antigen receptor \[CAR\] T cells). Patients who do not respond to Immunotherapy will receive Reintensification therapy. During Remission Induction therapy, prednisone dose is 40mg/m\^2 and 2 doses of daunorubicin are given. Dasatinib, ruxolitinib, and bortezomib are given as done for patients with standard-risk B-ALL but are discontinued in Immunotherapy and Reintensification therapy. Blinatumomab will be given to patients who are not able to receive CAR T cell therapy and patients with certain genetic subtypes and those with Down syndrome. Interventions: prednisone, vincristine, daunorubicin, pegaspargase (or Erwinase®, Rylaze™ or Calaspargase pegol), cyclophosphamide, cytarabine, mercaptopurine, dasatinib, bortezomib, ruxolitinib, blinatumomab, etoposide, dexamethasone, clofarabine, thioguanine, methotrexate.

Drug: Prednisone; Drug: Vincristine; Drug: Daunorubicin; Drug: Pegaspargase; Drug: Erwinase®; Drug: Cyclophosphamide; Drug: Cytarabine; Drug: Mercaptopurine; Drug: Dasatinib; Drug: Methotrexate; Drug: Blinatumomab; Drug: Ruxolitinib; Drug: Bortezomib; Drug: Dexamethasone; Drug: Etoposide; Drug: Clofarabine; Drug: Thioguanine; Drug: Asparaginase Erwinia chrysanthemi (recombinant)-rywn; Drug: Calaspargase Pegol

T-ALL and T-LLy, Standard-risk

EXPERIMENTAL

Induction (6 wks), Early Intensification (4 wks), Consolidation (8 wks), and Continuation (120 wks). During Remission Induction therapy, prednisone dose is 60mg/m\^2 and 3 doses daunorubicin are given. Dasatinib is given for patients with Ph+ and those with ABL-class fusion. Ruxolitinib is given for patients with activation of JAK-STAT signaling; ALL patients with Day 15 or Day 22 MRD ≥5% and all patients with ETP and T/M MPAL and LLy patients who don't qualify for complete response at end of Remission Induction. Bortezomib is given to patients without targetable lesions and Day 15 or Day 22 MRD ≥ 5%. Interventions: prednisone, vincristine, daunorubicin, pegaspargase (or Erwinase®, Rylaze™ or Calaspargase pegol), cyclophosphamide, cytarabine, mercaptopurine, dasatinib, bortezomib, ruxolitinib, methotrexate, dexamethasone, doxorubicin, nelarabine, thioguanine.

Drug: Prednisone; Drug: Vincristine; Drug: Daunorubicin; Drug: Pegaspargase; Drug: Erwinase®; Drug: Cyclophosphamide; Drug: Cytarabine; Drug: Mercaptopurine; Drug: Dasatinib; Drug: Methotrexate; Drug: Ruxolitinib; Drug: Bortezomib; Drug: Dexamethasone; Drug: Doxorubicin; Drug: Nelarabine; Drug: Thioguanine; Drug: Asparaginase Erwinia chrysanthemi (recombinant)-rywn; Drug: Calaspargase Pegol

T-ALL and T-LLy, High-risk

EXPERIMENTAL

Induction (6 wks), Early Intensification (4 wks), Consolidation (8 wks), and Reintensification. During Remission Induction therapy, prednisone dose is 60mg/m\^2 and 3 doses daunorubicin are given. Dasatinib, ruxolitinib, and bortezomib given as done for patients with standard-risk T-ALL but are discontinued in Reintensification therapy. Interventions: prednisone, vincristine, daunorubicin, pegaspargase (or Erwinase®, Rylaze™ or Calaspargase pegol), cyclophosphamide, cytarabine, mercaptopurine, dasatinib, bortezomib, ruxolitinib, methotrexate, etoposide, dexamethasone, clofarabine, vorinostat, idarubicin, nelarabine, thioguanine..

Drug: Prednisone; Drug: Vincristine; Drug: Daunorubicin; Drug: Pegaspargase; Drug: Erwinase®; Drug: Cyclophosphamide; Drug: Cytarabine; Drug: Mercaptopurine; Drug: Dasatinib; Drug: Methotrexate; Drug: Ruxolitinib; Drug: Bortezomib; Drug: Dexamethasone; Drug: Etoposide; Drug: Clofarabine; Drug: Vorinostat; Drug: Idarubicin; Drug: Nelarabine; Drug: Thioguanine; Drug: Asparaginase Erwinia chrysanthemi (recombinant)-rywn; Drug: Calaspargase Pegol

ALL, CEP72 T/T, Vincristine

EXPERIMENTAL

Patients with the CEP72 rs904627T/T genotype (\~16% of patients) will be randomized (unblinded design, only those who evaluate neuropathy are blinded) to receive either 1.5 mg/m\^2 or 1 mg/m\^2 of vincristine after Continuation Week 1. Patients in low- risk will complete vincristine in Week 49 and those in standard/high-risk will complete in Week 101. Intervention: vincristine.

Drug: Vincristine

ALL, CEP72 C/T or C/C, Vincristine

EXPERIMENTAL

Patients with either a CEP72 rs904627 C/T or C/C genotype (\~84% of patients) will be randomized (unblinded design, only those who evaluate neuropathy are blinded) to receive vincristine (2 mg/m\^2 per dose except during Reinduction I and Reinduction II when 3 weekly doses of 1.5 mg/m\^2 will be given) and dexamethasone pulses through Week 49 of Continuation Treatment or through Week 101 of Continuation Treatment. Patients at low-risk will complete vincristine in Week 49. Interventions: vincristine, dexamethasone, methotrexate, mercaptopurine.

Drug: Vincristine; Drug: Mercaptopurine; Drug: Methotrexate; Drug: Dexamethasone

Interventions

Prednisone DRUG

Given orally (PO).

Also known as: Prednisolone, Deltasone, Meticorten, Orasone®, Liquid Pred, Pediapred®, Sterapred®

B-ALL and B-LLy, High-risk; B-ALL and B-LLy, Low-risk; B-ALL and B-LLy, Standard-risk; T-ALL and T-LLy, High-risk; T-ALL and T-LLy, Standard-risk

Vincristine DRUG

Given intravenously (IV).

Also known as: Vincristine sulfate, Oncovin®, VCR, LCR

ALL, CEP72 C/T or C/C, Vincristine; ALL, CEP72 T/T, Vincristine; B-ALL and B-LLy, High-risk; B-ALL and B-LLy, Low-risk; B-ALL and B-LLy, Standard-risk; T-ALL and T-LLy, High-risk; T-ALL and T-LLy, Standard-risk

Daunorubicin DRUG

Given IV.

Also known as: Daunomycin, rubidomycin, Cerubidine®

B-ALL and B-LLy, High-risk; B-ALL and B-LLy, Low-risk; B-ALL and B-LLy, Standard-risk; T-ALL and T-LLy, High-risk; T-ALL and T-LLy, Standard-risk

Pegaspargase DRUG

Given IV or intramuscularly (IM) .

Also known as: PEG-asparaginase, PEGLA, PEG-L-asparaginase, polyethylene glycol-L-asparaginase, Oncaspar®

B-ALL and B-LLy, High-risk; B-ALL and B-LLy, Low-risk; B-ALL and B-LLy, Standard-risk; T-ALL and T-LLy, High-risk; T-ALL and T-LLy, Standard-risk

Erwinase® DRUG

To be used in case of hypersensitivity or intolerance to Pegaspargase or if Pegaspargase is not available. Given IV or intramuscularly (IM).

Also known as: Erwinia chrysanthemi, Asparaginase Erwinia chrysanthemi, Erwinaze^TM, Crisantaspase

B-ALL and B-LLy, High-risk; B-ALL and B-LLy, Low-risk; B-ALL and B-LLy, Standard-risk; T-ALL and T-LLy, High-risk; T-ALL and T-LLy, Standard-risk

Cyclophosphamide DRUG

Given IV.

Also known as: Cytoxan®

B-ALL and B-LLy, High-risk; B-ALL and B-LLy, Low-risk; B-ALL and B-LLy, Standard-risk; T-ALL and T-LLy, High-risk; T-ALL and T-LLy, Standard-risk

Cytarabine DRUG

Given IV or by subcutaneous injection (SQ).

Also known as: Cytosine arabinoside, Ara-C, Cytosar®

B-ALL and B-LLy, High-risk; B-ALL and B-LLy, Low-risk; B-ALL and B-LLy, Standard-risk; T-ALL and T-LLy, High-risk; T-ALL and T-LLy, Standard-risk

Mercaptopurine DRUG

Given PO.

Also known as: 6-MP, Purinethol®, Purixan^TM, 6-mercaptopurine

ALL, CEP72 C/T or C/C, Vincristine; B-ALL and B-LLy, High-risk; B-ALL and B-LLy, Low-risk; B-ALL and B-LLy, Standard-risk; T-ALL and T-LLy, High-risk; T-ALL and T-LLy, Standard-risk

Dasatinib DRUG

Given PO.

Also known as: Sprycel®

B-ALL and B-LLy, High-risk; B-ALL and B-LLy, Low-risk; B-ALL and B-LLy, Standard-risk; T-ALL and T-LLy, High-risk; T-ALL and T-LLy, Standard-risk

Methotrexate DRUG

Given IV.

Also known as: MTX, amethopterin, Trexall®

ALL, CEP72 C/T or C/C, Vincristine; B-ALL and B-LLy, High-risk; B-ALL and B-LLy, Low-risk; B-ALL and B-LLy, Standard-risk; T-ALL and T-LLy, High-risk; T-ALL and T-LLy, Standard-risk

Blinatumomab DRUG

Given IV.

Also known as: Blincyto®

B-ALL and B-LLy, High-risk; B-ALL and B-LLy, Low-risk; B-ALL and B-LLy, Standard-risk

Ruxolitinib DRUG

Given PO.

Also known as: Jakafi®

B-ALL and B-LLy, High-risk; B-ALL and B-LLy, Standard-risk; T-ALL and T-LLy, High-risk; T-ALL and T-LLy, Standard-risk

Bortezomib DRUG

Given IV or subcutaneously (SQ).

Also known as: Velcade®

B-ALL and B-LLy, High-risk; B-ALL and B-LLy, Standard-risk; T-ALL and T-LLy, High-risk; T-ALL and T-LLy, Standard-risk

Dexamethasone DRUG

Given PO.

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

ALL, CEP72 C/T or C/C, Vincristine; B-ALL and B-LLy, High-risk; B-ALL and B-LLy, Low-risk; B-ALL and B-LLy, Standard-risk; T-ALL and T-LLy, High-risk; T-ALL and T-LLy, Standard-risk

Doxorubicin DRUG

Given IV.

Also known as: Adriamycin®

B-ALL and B-LLy, Standard-risk; T-ALL and T-LLy, Standard-risk

Etoposide DRUG

Given IV.

Also known as: Etoposide Phosphate, VePesid®, Etopophos®, VP-16

B-ALL and B-LLy, High-risk; T-ALL and T-LLy, High-risk

Clofarabine DRUG

Given IV.

Also known as: Clolar®

B-ALL and B-LLy, High-risk; T-ALL and T-LLy, High-risk

Vorinostat DRUG

Given PO.

Also known as: Zolinza®, Suberoylanilide Hydroxamic Acid, SAHA

T-ALL and T-LLy, High-risk

Idarubicin DRUG

Given IV.

Also known as: Idarubicin HCl, 4-Demethoxydaunorubicin, 4-DMD, DMDR, Idamycin PFS®

T-ALL and T-LLy, High-risk

Nelarabine DRUG

Given IV.

Also known as: Arranon®, Atriance®, Compound 506U78

T-ALL and T-LLy, High-risk; T-ALL and T-LLy, Standard-risk

Thioguanine DRUG

Participants with mercaptopurine-related pancreatitis. Given PO.

Also known as: 6-thioguanine, Tioguanine, 2-amino-1,7-dihydro-6H-purine-6-thione, WR-1141, Tabloid®, Lanvis®

B-ALL and B-LLy, High-risk; B-ALL and B-LLy, Low-risk; B-ALL and B-LLy, Standard-risk; T-ALL and T-LLy, High-risk; T-ALL and T-LLy, Standard-risk

Asparaginase Erwinia chrysanthemi (recombinant)-rywn DRUG

To be used in case of hypersensitivity or intolerance to Pegaspargase or if Pegaspargase is not available. Given intramuscularly (IM).

Also known as: Rylaze™, Recombinant Erwinia

B-ALL and B-LLy, High-risk; B-ALL and B-LLy, Low-risk; B-ALL and B-LLy, Standard-risk; T-ALL and T-LLy, High-risk; T-ALL and T-LLy, Standard-risk

Calaspargase Pegol DRUG

To be used in case of hypersensitivity or intolerance to Pegaspargase or if Pegaspargase is not available. Given IV.

Also known as: ASPARLAS

B-ALL and B-LLy, High-risk; B-ALL and B-LLy, Low-risk; B-ALL and B-LLy, Standard-risk; T-ALL and T-LLy, High-risk; T-ALL and T-LLy, Standard-risk

Eligibility Criteria

• Age: 1 Year - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Diagnosis of B- or T-ALL or LLy by immunophenotyping:
• LLy participants must have \< 25% tumor cells in bone marrow and peripheral blood by morphology and flow cytometry. If any of these show ≥25% blasts, patient will be considered to have leukemia. Patients with MPAL are eligible.
• Age 1-18 years (inclusive).
• No prior therapy, or limited prior therapy, including systemic glucocorticoids for one week or less, one dose of vincristine, emergency radiation therapy (e.g., to the mediastinum, head and neck, orbit, etc.) and one dose of intrathecal chemotherapy.
• Written, informed consent and assent following Institutional Review Board (IRB), National Cancer Institute (NCI), Food and Drug Administration (FDA), and Office of Human Research Protections (OHRP) Guidelines.

You may not qualify if:

• Participants who are pregnant or lactating. Males or females of reproductive potential must agree to use effective contraception for the duration of study participation.
• Inability or unwillingness of research participant or legal guardian/representative to give written informed consent.

Sponsors & Collaborators

• St. Jude Children's Research Hospital: lead
• Incyte Corporation: collaborator
• Amgen: collaborator
• Servier: collaborator

Study Sites (8)

Lucile Packard Children's Hospital Stanford University

Palo Alto, California, 94305, United States

Location

Rady Children's Hospital San Diego

San Diego, California, 92123, United States

Location

Children's Hospital of Illinois at OSF-Saint Francis Medical Center (St. Jude Midwest Affiliate - Peoria)

Peoria, Illinois, 61637, United States

Location

Children's Hospital of Michigan

Detroit, Michigan, 48201, United States

Location

St. Jude Affiliate Clinic - Novant Health Hemby Children's Hospital

Charlotte, North Carolina, 28204, United States

Location

St. Jude Children's Research Hospital

Memphis, Tennessee, 38105, United States

Location

Cook Children's Medical Center

Fort Worth, Texas, 76104, United States

Location

The Royal Children's Hospital Melbourne

Parkville, Victoria, 3052, Australia

Location

Related Links

• St. Jude Children's Research Hospital
• ClinicalTrials Open at St. Jude

MeSH Terms

Conditions

Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia; Lymphoma

Interventions

Prednisone; Prednisolone; prednisolone phosphate; Vincristine; Daunorubicin; pegaspargase; Asparaginase; asparaginase erwinia chrysanthemi recombinant; Cyclophosphamide; Cytarabine; Mercaptopurine; Dasatinib; Methotrexate; blinatumomab; ruxolitinib; Bortezomib; Dexamethasone; Calcium Dobesilate; Doxorubicin; Etoposide; etoposide phosphate; Clofarabine; Vorinostat; Idarubicin; nelarabine; Thioguanine; calaspargase pegol

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

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

Study Officials

• Hiroto Inaba, MD, PhD

  St. Jude Children's Research Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: Only certain outcome measures as indicated will be blinded to the outcomes assessor.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 27, 2017
• First Posted: April 18, 2017
• Study Start: March 29, 2017
• Primary Completion (Estimated): September 30, 2026
• Study Completion (Estimated): September 30, 2028
• Last Updated: December 5, 2025

Record last verified: 2025-12

Locations

US (7); AU (1)