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Enzyme

Total Therapy XVII for Leukemia

Phase 2 & 3
Waitlist Available
Led By Hiroto Inaba, MD, PhD
Research Sponsored by St. Jude Children's Research Hospital
Eligibility Criteria Checklist
Specific guidelines that determine who can or cannot participate in a clinical trial
Must have
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
Must not have
Inability or unwillingness of research participant or legal guardian/representative to give written informed consent
Timeline
Screening 3 weeks
Treatment Varies
Follow Up from baseline to week 49 continuation treatment (up to 6 months after last patient completes week 49 continuation)
Awards & highlights

Summary

This trial is using 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).

Who is the study for?
This trial is for children aged 1-18 with newly diagnosed B-cell or T-cell acute lymphoblastic leukemia (ALL) or lymphoma, who haven't had much treatment before. They must be able to give consent and not be pregnant, breastfeeding, or unwilling to use contraception.
What is being tested?
The study tests a combination of drugs like Calaspargase Pegol and Bortezomib among others, aiming to improve survival rates by targeting specific genetic features of the leukemia. It includes precision medicine strategies and therapies such as CAR T cells for certain patients.
What are the potential side effects?
Potential side effects include allergic reactions to medication components, nerve damage from drugs like Vincristine, increased risk of infections due to immune system suppression, liver problems from medications like Methotrexate and Mercaptopurine.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below
Select...
I have been diagnosed with a type of leukemia.
Select...
My cancer has less than 25% tumor cells in my bone marrow and blood.
Select...
I am between 1 and 18 years old.
Select...
I have been diagnosed with mixed phenotype acute leukemia (MPAL).

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:
Select...
I cannot or do not want to give my consent to participate.

Timeline

Screening ~ 3 weeks
Treatment ~ Varies
Follow Up ~at 6 months after the last randomized patient completes continuation treatment (week 120).
This trial's timeline: 3 weeks for screening, Varies for treatment, and at 6 months after the last randomized patient completes continuation treatment (week 120). for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.
Primary study objectives
Cumulative incidence of Grade 2 or higher neuropathy in patients with CEP72 CC or CT genotype
Event-free survival of ALL patients (EFS)
Proportion of patients with CEP72TT genotype who develop two or more episodes of Grade 2 or higher neuropathy during Continuation
Secondary study objectives
5-year OS of LLy patients
5-year overall survival (OS) of ALL patients compared to historical controls
Change in bone mineral density (BMD) in the tibia
+10 more
Other study objectives
5-year EFS of MPAL patients
5-year OS of MPAL patients
Log odds ratio of pharmacodynamic predictors of treatment outcome (host toxicity or in vivo efficacy)
+4 more

Side effects data

From 2022 Phase 3 trial • 402 Patients • NCT03110562
50%
Thrombocytopenia
45%
Anaemia
39%
Nausea
29%
Decreased appetite
29%
Diarrhoea
27%
Weight decreased
24%
Vomiting
24%
Neuropathy peripheral
23%
Fatigue
21%
Cataract
21%
Neutropenia
15%
Asthenia
12%
Upper respiratory tract infection
11%
Constipation
11%
Pyrexia
8%
Oedema peripheral
8%
Pneumonia
6%
Dehydration
6%
Back pain
6%
Dizziness
6%
Lymphopenia
6%
Leukopenia
6%
Cough
6%
Insomnia
6%
Bronchitis
5%
Abdominal pain
5%
Acute kidney injury
5%
Muscular weakness
5%
Lower respiratory tract infection
3%
Pain in extremity
3%
Hyperglycaemia
3%
Hyponatraemia
3%
Hypertension
3%
Urinary tract infection
3%
Toothache
3%
Disturbance in attention
3%
Sepsis
3%
Nasopharyngitis
3%
Cardiac failure
2%
Confusional state
2%
Embolism
2%
Peripheral swelling
2%
Hyperkalaemia
2%
Multiple fractures
2%
Haemoglobin decreased
2%
Infection
2%
Blood creatinine increased
2%
Paraesthesia
2%
Respiratory syncytial virus infection
2%
Ischaemic stroke
2%
Cerebrovascular accident
2%
Cerebral haemorrhage
2%
Sudden death
2%
C-reactive protein increased
2%
Syncope
2%
Cognitive disorder
2%
Influenza
2%
Septic shock
2%
Clostridium difficile infection
2%
Pulmonary contusion
2%
Blood uric acid increased
2%
Oropharyngeal pain
2%
Dyspepsia
2%
Taste disorder
2%
Myocardial infarction
2%
Cardiac failure acute
2%
Bronchitis viral
2%
Compression fracture
2%
Osteonecrosis of jaw
2%
Depression
100%
80%
60%
40%
20%
0%
Study treatment Arm
SVdX Arm: Selinexor + Bortezomib + Dexamethasone
SdX Arm: Selinexor + Dexamethasone
SVd Arm: Selinexor + Bortezomib + Dexamethasone
Vd Arm: Bortezomib + Dexamethasone

Trial Design

7Treatment groups
Experimental Treatment
Group I: T-ALL and T-LLy, Standard-riskExperimental Treatment18 Interventions
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.
Group II: T-ALL and T-LLy, High-riskExperimental Treatment21 Interventions
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..
Group III: B-ALL and B-LLy, Standard-riskExperimental Treatment18 Interventions
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
Group IV: B-ALL and B-LLy, Low-riskExperimental Treatment15 Interventions
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.
Group V: B-ALL and B-LLy, High-riskExperimental Treatment19 Interventions
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.
Group VI: ALL, CEP72 T/T, VincristineExperimental Treatment1 Intervention
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.
Group VII: ALL, CEP72 C/T or C/C, VincristineExperimental Treatment4 Interventions
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.
Treatment
First Studied
Drug Approval Stage
How many patients have taken this drug
Bortezomib
2005
Completed Phase 3
~1410
Idarubicin
2014
Completed Phase 4
~4330
Nelarabine
2008
Completed Phase 2
~500
Thioguanine
2012
Completed Phase 4
~10830
Vincristine
2003
Completed Phase 4
~2970
Prednisone
2014
Completed Phase 4
~2500
Daunorubicin
2013
Completed Phase 4
~5040
Pegaspargase
2005
Completed Phase 3
~9260
Cytarabine
2016
Completed Phase 3
~3330
Methotrexate
2019
Completed Phase 4
~4400
Blinatumomab
2014
Completed Phase 3
~1230
Etoposide
2010
Completed Phase 3
~2960
Ruxolitinib
2018
Completed Phase 3
~1140
Dexamethasone
2007
Completed Phase 4
~2640
Mercaptopurine
2012
Completed Phase 4
~12550
Clofarabine
2007
Completed Phase 3
~1130
Vorinostat
2014
Completed Phase 3
~1600
Doxorubicin
2012
Completed Phase 3
~8030
Cyclophosphamide
2010
Completed Phase 4
~2320
Dasatinib
2012
Completed Phase 3
~2320

Find a Location

Who is running the clinical trial?

ServierIndustry Sponsor
50 Previous Clinical Trials
43,469 Total Patients Enrolled
St. Jude Children's Research HospitalLead Sponsor
442 Previous Clinical Trials
5,308,079 Total Patients Enrolled
Incyte CorporationIndustry Sponsor
382 Previous Clinical Trials
56,262 Total Patients Enrolled

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