Therapy for Newly Diagnosed Patients With B-Cell Precursor Acute Lymphoblastic Leukemia and Lymphoma

Phase 2

Not yet recruiting

• Conditions: Lymphoblastic Lymphoma; Acute Lymphoblastic Leukemia
• Interventions: Drug: Dexamethasone; Drug: Vincristine; Drug: Inotuzumab; Drug: Blinatumomab; Drug: Dasatinib; Procedure: IT MHA; Drug: Cyclophosphamide; Drug: Cytarabine; Drug: Methotrexate; Drug: 6-Mercaptopurine; Drug: Calaspargase; Drug: Daunorubicin; Drug: Thioguanine

• Registration Number: NCT06533748
• Lead Sponsor: St. Jude Children's Research Hospital

Brief Summary

This is a Phase II clinical trial testing the use of two antigen-directed therapies, inotuzumab and blinatumomab, as part of induction therapy for children and young adults with newly diagnosed B-cell precursor acute lymphoblastic leukemia and lymphoma.

Primary Objective
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Detailed Description

This study utilizes a single arm phase II design. Treatment will consist of 3 main phases: Induction, early post induction \[including Consolidation, Blinatumomab 1, High-Dose Methotrexate, Reinduction, Interim, Reconsolidation, and Blinatumomab 2\], and Maintenance.

Induction:
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Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study First Submitted: 2024-07-30
• Study First Submitted QC: 2024-07-30
• Study First Posted: 2024-08-01
• Status Verified: 2024-11
• Last Update Submitted: 2024-11-07
• Last Update Posted: 2024-11-08
• Study Start: 2024-12
• Primary Completion: 2028-05
• Study Completion: 2034-05

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 128

Inclusion Criteria

• Enrollment on INITIALL.

• Age 1-18.99 years at the time of enrollment on INITIALL.

• B-Acute lymphoblastic leukemia or lymphoblastic lymphoma.

• No prior chemotherapy excluding therapy given on or allowed by INITIALL.

• NCI high-risk (age 10 years or greater or presenting WBC count ≥50,000 cells/microL) or NCI standard-risk and a HR clinical feature as listed below:

  • CNS3 disease (≥5 WBC/microL CSF with blasts present)
  • Testicular involvement of leukemia
  • Steroid pretreatment defined as >24 hours of therapy in the 14 days prior to enrollment on INITIALL if a preceding WBC to define NCI risk is unavailable

• For lymphoblastic lymphoma, Stage 3-4 disease OR Stage 1-2 disease in patient ages ≥10 years OR HR clinical feature as defined above.

• Adequate liver function defined as:

  • Direct bilirubin ≤ 1.5x the upper limit of normal for age and alanine transaminase (ALT) ≤ 5x the upper limit of normal for age.
  • Patients with ALT or aspartate transferase (AST) 2.5-5x the upper limit of normal for age are ineligible unless the increase is attributable to hemolysis.

• Adequate renal function defined as:

  • Calculated glomerular filtration rate (GFR) ≥ 50 mL/min/1.73m^2 using the Bedside Schwartz equation OR creatinine below or equal to the maximum defined below:

    • Age: 1 to <2 years; maximum serum creatinine (mg/dL): 0.6 (male and female)
    • Age: 2 to <6 years; maximum serum creatinine (mg/dL): 0.8 (male and female)
    • Age: 6 to <10 years; maximum serum creatinine (mg/dL): 1.0 (male and female)
    • Age: 10 to <13 years; maximum serum creatinine (mg/dL): 1.2 (male and female)
    • Age: 13 to <16 years; maximum serum creatinine (mg/dL): 1.5 (male); 1.4 (female)
    • Age: ≥16 years; maximum serum creatinine (mg/dL): 1.7 (male); 1.4 (female)

• Eligibility for inclusion post-induction requires meeting the first 4 Inclusion criteria above AND:

  • Treatment on SJALL23H for Induction OR

  • Lymphoblastic lymphoma, initially treated on an SJALL protocol OR standard (non-protocol) therapy, without a complete response at the end of induction OR

  • NCI-SR ALL at diagnosis and treated with an SJALL protocol OR standard (non-protocol) therapy who have

    • Slow response to therapy (≥0.1% MRD at end of induction for patients with hyperdiploid ALL or ≥0.01% MRD at end of induction for others with ALL) OR
    • HR genetics as defined in the protocol.

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Exclusion Criteria

• Presence of ETV6::RUNX1 fusion unless also having a HR clinical feature OR slow response to induction therapy.
• History or presence of clinically relevant central nervous system (CNS) pathology or event such as epilepsy, childhood or adult non-febrile seizure, paresis, aphasia, stroke, severe brain injuries, dementia, Parkinson's disease, cerebellar disease, organic brain syndrome, or psychosis. History of simple febrile seizure during childhood and presence of CNS leukemia at diagnosis are not exclusions to participation.
• Active uncontrolled infection.
• Current active autoimmune disease or history of autoimmune disease with the potential for CNS involvement.
• History of venoocclusive disease/ sinusoidal obstructive syndrome.
• Unstable cardiac disease including QTc >500msec.
• Inability or unwillingness to give informed consent/ assent as applicable.
• Pregnant or lactating.
• For patients of reproductive potential, unwillingness to use effective contraception for the duration of protocol therapy.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
SJALL23H Treated Patients	Dexamethasone	All eligible patients receive intervention according to the Detailed Description section with the following: Induction: Dexamethasone, Vincristine, Inotuzumab, Blinatumomab, Dasatinib, IT MHA. Early Post Induction: Cyclophosphamide, Cytarabine, Inotuzumab, Methotrexate, IT MHA, Dasatinib, Blinatumomab, 6-mercaptopurine, Dexamethasone, Vincristine, Daunorubicin, Calaspargase. Maintenance: Dexamethasone, Vincristine, Methotrexate, 6-mercaptopurine, Thioguanine, Dasatinib, IT MHA.
SJALL23H Treated Patients	Vincristine	All eligible patients receive intervention according to the Detailed Description section with the following: Induction: Dexamethasone, Vincristine, Inotuzumab, Blinatumomab, Dasatinib, IT MHA. Early Post Induction: Cyclophosphamide, Cytarabine, Inotuzumab, Methotrexate, IT MHA, Dasatinib, Blinatumomab, 6-mercaptopurine, Dexamethasone, Vincristine, Daunorubicin, Calaspargase. Maintenance: Dexamethasone, Vincristine, Methotrexate, 6-mercaptopurine, Thioguanine, Dasatinib, IT MHA.
SJALL23H Treated Patients	Inotuzumab	All eligible patients receive intervention according to the Detailed Description section with the following: Induction: Dexamethasone, Vincristine, Inotuzumab, Blinatumomab, Dasatinib, IT MHA. Early Post Induction: Cyclophosphamide, Cytarabine, Inotuzumab, Methotrexate, IT MHA, Dasatinib, Blinatumomab, 6-mercaptopurine, Dexamethasone, Vincristine, Daunorubicin, Calaspargase. Maintenance: Dexamethasone, Vincristine, Methotrexate, 6-mercaptopurine, Thioguanine, Dasatinib, IT MHA.
SJALL23H Treated Patients	Blinatumomab	All eligible patients receive intervention according to the Detailed Description section with the following: Induction: Dexamethasone, Vincristine, Inotuzumab, Blinatumomab, Dasatinib, IT MHA. Early Post Induction: Cyclophosphamide, Cytarabine, Inotuzumab, Methotrexate, IT MHA, Dasatinib, Blinatumomab, 6-mercaptopurine, Dexamethasone, Vincristine, Daunorubicin, Calaspargase. Maintenance: Dexamethasone, Vincristine, Methotrexate, 6-mercaptopurine, Thioguanine, Dasatinib, IT MHA.
SJALL23H Treated Patients	Dasatinib	All eligible patients receive intervention according to the Detailed Description section with the following: Induction: Dexamethasone, Vincristine, Inotuzumab, Blinatumomab, Dasatinib, IT MHA. Early Post Induction: Cyclophosphamide, Cytarabine, Inotuzumab, Methotrexate, IT MHA, Dasatinib, Blinatumomab, 6-mercaptopurine, Dexamethasone, Vincristine, Daunorubicin, Calaspargase. Maintenance: Dexamethasone, Vincristine, Methotrexate, 6-mercaptopurine, Thioguanine, Dasatinib, IT MHA.
SJALL23H Treated Patients	IT MHA	All eligible patients receive intervention according to the Detailed Description section with the following: Induction: Dexamethasone, Vincristine, Inotuzumab, Blinatumomab, Dasatinib, IT MHA. Early Post Induction: Cyclophosphamide, Cytarabine, Inotuzumab, Methotrexate, IT MHA, Dasatinib, Blinatumomab, 6-mercaptopurine, Dexamethasone, Vincristine, Daunorubicin, Calaspargase. Maintenance: Dexamethasone, Vincristine, Methotrexate, 6-mercaptopurine, Thioguanine, Dasatinib, IT MHA.
SJALL23H Treated Patients	Cytarabine	All eligible patients receive intervention according to the Detailed Description section with the following: Induction: Dexamethasone, Vincristine, Inotuzumab, Blinatumomab, Dasatinib, IT MHA. Early Post Induction: Cyclophosphamide, Cytarabine, Inotuzumab, Methotrexate, IT MHA, Dasatinib, Blinatumomab, 6-mercaptopurine, Dexamethasone, Vincristine, Daunorubicin, Calaspargase. Maintenance: Dexamethasone, Vincristine, Methotrexate, 6-mercaptopurine, Thioguanine, Dasatinib, IT MHA.
SJALL23H Treated Patients	Methotrexate	All eligible patients receive intervention according to the Detailed Description section with the following: Induction: Dexamethasone, Vincristine, Inotuzumab, Blinatumomab, Dasatinib, IT MHA. Early Post Induction: Cyclophosphamide, Cytarabine, Inotuzumab, Methotrexate, IT MHA, Dasatinib, Blinatumomab, 6-mercaptopurine, Dexamethasone, Vincristine, Daunorubicin, Calaspargase. Maintenance: Dexamethasone, Vincristine, Methotrexate, 6-mercaptopurine, Thioguanine, Dasatinib, IT MHA.
SJALL23H Treated Patients	6-Mercaptopurine	All eligible patients receive intervention according to the Detailed Description section with the following: Induction: Dexamethasone, Vincristine, Inotuzumab, Blinatumomab, Dasatinib, IT MHA. Early Post Induction: Cyclophosphamide, Cytarabine, Inotuzumab, Methotrexate, IT MHA, Dasatinib, Blinatumomab, 6-mercaptopurine, Dexamethasone, Vincristine, Daunorubicin, Calaspargase. Maintenance: Dexamethasone, Vincristine, Methotrexate, 6-mercaptopurine, Thioguanine, Dasatinib, IT MHA.
SJALL23H Treated Patients	Calaspargase	All eligible patients receive intervention according to the Detailed Description section with the following: Induction: Dexamethasone, Vincristine, Inotuzumab, Blinatumomab, Dasatinib, IT MHA. Early Post Induction: Cyclophosphamide, Cytarabine, Inotuzumab, Methotrexate, IT MHA, Dasatinib, Blinatumomab, 6-mercaptopurine, Dexamethasone, Vincristine, Daunorubicin, Calaspargase. Maintenance: Dexamethasone, Vincristine, Methotrexate, 6-mercaptopurine, Thioguanine, Dasatinib, IT MHA.
SJALL23H Treated Patients	Cyclophosphamide	All eligible patients receive intervention according to the Detailed Description section with the following: Induction: Dexamethasone, Vincristine, Inotuzumab, Blinatumomab, Dasatinib, IT MHA. Early Post Induction: Cyclophosphamide, Cytarabine, Inotuzumab, Methotrexate, IT MHA, Dasatinib, Blinatumomab, 6-mercaptopurine, Dexamethasone, Vincristine, Daunorubicin, Calaspargase. Maintenance: Dexamethasone, Vincristine, Methotrexate, 6-mercaptopurine, Thioguanine, Dasatinib, IT MHA.
SJALL23H Treated Patients	Daunorubicin	All eligible patients receive intervention according to the Detailed Description section with the following: Induction: Dexamethasone, Vincristine, Inotuzumab, Blinatumomab, Dasatinib, IT MHA. Early Post Induction: Cyclophosphamide, Cytarabine, Inotuzumab, Methotrexate, IT MHA, Dasatinib, Blinatumomab, 6-mercaptopurine, Dexamethasone, Vincristine, Daunorubicin, Calaspargase. Maintenance: Dexamethasone, Vincristine, Methotrexate, 6-mercaptopurine, Thioguanine, Dasatinib, IT MHA.
SJALL23H Treated Patients	Thioguanine	All eligible patients receive intervention according to the Detailed Description section with the following: Induction: Dexamethasone, Vincristine, Inotuzumab, Blinatumomab, Dasatinib, IT MHA. Early Post Induction: Cyclophosphamide, Cytarabine, Inotuzumab, Methotrexate, IT MHA, Dasatinib, Blinatumomab, 6-mercaptopurine, Dexamethasone, Vincristine, Daunorubicin, Calaspargase. Maintenance: Dexamethasone, Vincristine, Methotrexate, 6-mercaptopurine, Thioguanine, Dasatinib, IT MHA.

Primary Outcome Measures

Name	Time	Method
End of induction minimal residual disease negative remission	On treatment to end of induction, approximately 29 days	Flow cytometry (preferred) or next generation sequencing measurement of bone marrow with \<0.01% leukemia with resolution of extramedullary disease at the end of induction (approximately day 29) and will be analyzed within 6 months of the last participant reaching the timepoint.

Secondary Outcome Measures

Name	Time	Method
Comparison of MRD-negative rates to those on Total 17	On treatment to end of induction, approximately 29 days	Flow cytometry (preferred) or next generation sequencing measurement of bone marrow with \<0.01% leukemia with resolution of extramedullary disease will be compared between patients enrolled on this trial and patients with similar clinical features (age, WBC at diagnosis, CNS status, testicular involvement) enrolled on Total 17(NCT03117751).
Compare significant toxicities experienced to those on Total 17	On treatment to end of reconsolidation, approximately 56 days.	We will compare CTCAE version 5 clinically significant, non-hematological grade 3 or any non-hematological grade 4-5 toxicities. This comparison will encompass 3 periods: induction/ consolidation, reinduction, and reconsolidation.
Event free survival (EFS)	3.5 years after enrollment.	Kaplan-Meier estimates of the survival functions for event-free survival (EFS) will be calculated along with standard error. For EFS, death due to any cause, any relapse, consolidation failure, and second malignancy are considered as failure; patients remaining failure-free at the last follow up are censored.
Overall survival (OS)	3.5 years after enrollment.	Kaplan-Meier estimates of the survival functions for overall survival (OS) will be calculated along with standard error. For OS, only death due to any cause is considered as failure and patients still alive at the last follow up are censored.

Trial Locations

Locations (1)

St. Jude Children's Research Hospital; 🇺🇸 Memphis, Tennessee, United States