Total Therapy XVII for Leukemia

Not currently recruiting at 8 trial locations

Overseen By Hiroto Inaba, MD, PhD

Age: < 65

Sex: Any

Trial Phase: Phase 2 & 3

Sponsor: St. Jude Children's Research Hospital

Disqualifiers: Pregnancy, Lactation, Consent issues

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to improve treatment for children with acute lymphoblastic leukemia (ALL) or acute lymphoblastic lymphoma (LLy) through new precision medicine approaches. It explores various drug combinations, some targeting specific genetic features, to enhance cure rates and quality of life. The trial organizes participants into groups based on risk level and genetic markers, with some receiving experimental therapies like CAR T-cell therapy or new drug combinations. Children diagnosed with B- or T-ALL or LLy, who have had little or no prior treatment, may qualify for this trial. As a Phase 2 and Phase 3 trial, it evaluates the treatment's effectiveness in a smaller group and represents the final step before FDA approval, offering participants access to potentially groundbreaking therapies.

Will I have to stop taking my current medications?

The trial protocol does not specify whether you need to stop taking your current medications. However, it mentions that participants should have no prior therapy or limited prior therapy, which might imply some restrictions. It's best to discuss your current medications with the trial team for specific guidance.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that many treatments in this trial have been studied before, yielding different safety results.

For example, blinatumomab has effectively treated B-cell acute lymphoblastic leukemia (ALL). However, about 12.5% of patients experienced serious side effects like confusion and seizures. Despite these risks, blinatumomab is generally considered manageable.

Bortezomib, often used with other treatments for leukemia, has demonstrated effectiveness. However, it can cause severe side effects, especially in later treatment stages, such as blood disorders and low blood cell counts.

Dasatinib is another drug used for certain leukemias in both children and adults. It can cause decreased bone marrow activity, bleeding, and fluid retention. Despite these side effects, it remains an option for treating resistant leukemia types.

Ruxolitinib has shown promise when combined with chemotherapy for certain leukemias. While effective, it can lead to serious side effects like a higher risk of infections and low red blood cell count.

Nelarabine is used for certain T-cell leukemias and lymphomas. It can be effective, but side effects like infections and fever are common. Monitoring these during treatment is important.

These treatments are part of a clinical trial, meaning their safety and effectiveness are still under study. However, past research provides an idea of what to expect. Participants should discuss potential side effects with their medical team to understand the risks and benefits. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the treatments in the Total Therapy XVII for Leukemia trial because they incorporate innovative approaches that go beyond traditional chemotherapy. Unlike standard immunotherapy options, this trial includes CAR T-cell therapy, which engineers a patient's own immune cells to better target and destroy cancer cells. Additionally, the use of Blinatumomab, a bispecific T-cell engager, helps direct the body's immune cells to attack leukemia cells specifically. Another unique aspect is the inclusion of targeted therapies like Dasatinib and Ruxolitinib, which are designed to disrupt specific pathways that leukemia cells use to grow and survive. These treatments offer hope for more effective and personalized leukemia care.

What evidence suggests that this trial's treatments could be effective for leukemia and lymphoma?

Research has shown that several new treatments hold promise for acute lymphoblastic leukemia (ALL) and lymphoblastic lymphoma (LLy). This trial studies Blinatumomab, a type of immunotherapy, for its potential to improve outcomes in children with relapsed B-cell ALL. Studies indicate it can lead to disease-free survival rates of over 50%. Bortezomib, another treatment option in this trial, has proven effective when combined with other chemotherapy drugs, helping some leukemia patients achieve remission. Asparaginases, such as Asparaginase Erwinia chrysanthemi, are also under evaluation for their success in treating ALL, known for their prolonged activity in the body. Ruxolitinib, a JAK inhibitor included in this trial, has shown success in treating certain genetic types of leukemia. Each treatment targets specific features of leukemia cells, aiming to improve survival and reduce the risk of disease recurrence. ^{2 6 7 8 9}

Who Is on the Research Team?

Hiroto Inaba, MD, PhD

Principal Investigator

St. Jude Children's Research Hospital

Are You a Good Fit for This Trial?

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.

Inclusion Criteria

I have been diagnosed with a type of leukemia.

My cancer has less than 25% tumor cells in my bone marrow and blood.

I have been diagnosed with mixed phenotype acute leukemia (MPAL).

Exclusion Criteria

I cannot or do not want to give my consent to participate.

Participants who are pregnant or lactating. Males or females of reproductive potential must agree to use effective contraception for the duration of study participation

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Remission Induction

Initial treatment phase with prednisone, vincristine, daunorubicin, and pegaspargase to induce remission

6 weeks

Weekly visits for drug administration

Early Intensification

Additional therapy for patients with standard/high-risk or low-risk with specific MRD levels

4 weeks

Frequent visits for monitoring and drug administration

Consolidation

High dose methotrexate and other drugs to consolidate remission

8 weeks

Bi-weekly visits for high dose methotrexate

Continuation

Long-term risk-directed therapy to maintain remission

120 weeks

Regular visits for ongoing treatment and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

What Are the Treatments Tested in This Trial?

Interventions

• Asparaginase Erwinia chrysanthemi (recombinant)-rywn
• Blinatumomab
• Bortezomib
• Calaspargase Pegol
• CAR T-cell / Blinatumomab
• Clofarabine
• Cyclophosphamide
• Cytarabine
• Dasatinib
• Daunorubicin
• Dexamethasone
• Doxorubicin
• Erwinase®
• Idarubicin
• Mercaptopurine
• Methotrexate
• Nelarabine
• Pegaspargase
• Quality-of-Life Assessment
• Ruxolitinib
• Thioguanine
• Vorinostat

Trial Overview 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.

How Is the Trial Designed?

Group I: T-ALL and T-LLy, Standard-risk Experimental Treatment 18 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-risk Experimental Treatment 21 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-risk Experimental Treatment 18 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-risk Experimental Treatment 15 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-risk Experimental Treatment 19 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, Vincristine Experimental Treatment 1 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, Vincristine Experimental Treatment 4 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.

Who Is Running the Clinical Trial?

St. Jude Children's Research Hospital

Lead Sponsor

Trials

451

Recruited

5,326,000+

Servier

Industry Sponsor

Trials

55

Recruited

45,600+

Incyte Corporation

Industry Sponsor

Trials

408

Recruited

66,800+

Steven Stein

Incyte Corporation

Chief Medical Officer since 2015

MD from University of Witwatersrand

Hervé Hoppenot

Incyte Corporation

Chief Executive Officer since 2014

MBA from ESSEC Business School

Amgen

Industry Sponsor

Trials

1,508

Recruited

1,433,000+

Founded

1980

Headquarters

Thousand Oaks, USA

Known For

Human Therapeutics

Top Products

Enbrel, Prolia, Neulasta, Otezla

Robert A. Bradway

Amgen

Chief Executive Officer since 2012

MBA from Harvard Business School

Paul Burton

Amgen

Chief Medical Officer since 2023

MD from University of London, PhD in Molecular and Cellular Biology from Imperial College London

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10651770/

Recombinant Erwinia asparaginase (JZP458) in acute ... Intramuscular JZP458 at 25/25/50 mg/m2 M/W/F was effective in patients with ALL/LBL, with a safety profile similar to other asparaginases.

2. aetna.com aetna.com/cpb/medical/data/800_899/0864.html

Asparaginase Erwinia Chrysanthemi (Recombinant)-rywn ... Emadi et al (2014) stated that asparaginases are among the most effective agents against acute lymphoblastic leukemia (ALL) and are Food and Drug Administration ...

3. ashpublications.org ashpublications.org/bloodadvances/article/9/1/66/525802/Recombinant-Erwinia-asparaginase-JZP458-in-ALL-LBL

Recombinant Erwinia asparaginase (JZP458) in ALL/LBL ... AALL1931 investigated the efficacy and safety of recombinant Erwinia asparaginase (JZP458) in patients with acute lymphoblastic leukemia/lymphoblastic lymphoma.

4. ascopost.com ascopost.com/issues/august-10-2021/asparaginase-erwinia-chrysanthemi-recombinant-rywn-for-acute-lymphoblastic-leukemia-and-lymphoblastic-lymphoma/

Asparaginase Erwinia Chrysanthemi (Recombinant)-rywn ... The main efficacy outcome measure was demonstration of achievement and maintenance of nadir serum asparaginase activity ≥ 0.1 U/mL. The results ...

5. fda.gov fda.gov/drugs/resources-information-approved-drugs/fda-approves-asparaginase-erwinia-chrysanthemi-recombinant-leukemia-and-lymphoma

FDA approves asparaginase erwinia chrysanthemi ... FDA approves asparaginase erwinia chrysanthemi (recombinant) for leukemia and lymphoma. On June 30, 2021, the Food and Drug Administration ...

6. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2022/761179s001lbl.pdf

HIGHLIGHTS OF PRESCRIBING INFORMATION These ... Risk Summary. There are no data on the presence of asparaginase erwinia chrysanthemi (recombinant)-rywn in human milk, the effects on the breastfed child, or ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT07133997

Recombinant Erwinia Asparaginase and Venetoclax in ... Giving asparaginase Erwinia chrysanthemi and venetoclax in combination with blinatumomab may be safe, tolerable, and/or effective in treating ...

8. ashpublications.org ashpublications.org/blood/article/142/Supplement%201/1498/501397/Efficacy-and-Safety-of-Recombinant-Erwinia

Efficacy and Safety of Recombinant Erwinia Asparaginase ... It is used in treatment of patients with acute lymphoblastic leukemia/lymphoblastic lymphoma who developed hypersensitivity/silent inactivation ...

9. mayoclinic.org mayoclinic.org/drugs-supplements/asparaginase-erwinia-chrysanthemi-recombinant-rywn-intramuscular-route/description/drg-20518743

Asparaginase erwinia chrysanthemi recombinant-rywn ... Asparaginase Erwinia chrysanthemi recombinant-rywn is used together with other cancer medicines to treat certain types of blood cancer called acute ...