Adding Dasatinib Or Venetoclax To Improve Responses In Children With Newly Diagnosed T-Cell Acute Lymphoblastic Leukemia (ALL) Or Lymphoma (T-LLY) Or Mixed Phenotype Acute Leukemia (MPAL)

NCT ID: NCT06390319

Last Updated: 2025-09-23

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE2

Total Enrollment

100 participants

Study Classification

INTERVENTIONAL

Study Start Date

2024-12-27

Study Completion Date

2033-12-31

Brief Summary

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This is a clinical trial testing whether the addition of one of two chemotherapy agents, dasatinib or venetoclax, can improve outcomes for children and young adults with newly diagnosed T-cell acute lymphoblastic leukemia and lymphoma or mixed phenotype acute leukemia.

Primary Objective

* To evaluate if the end of induction MRD-negative rate is higher in patients with T-ALL treated with dasatinib compared to similar patients treated with 4-drug induction on AALL1231.
* To evaluate if the end of induction MRD-negative rate is higher in patients with ETP or near-ETP ALL treated with venetoclax compared to similar patients treated with 4-drug induction on AALL1231.

Secondary Objectives

* To assess the event free and overall survival of patients treated with this therapy.
* To compare grade 4 toxicities, event-free survival (EFS) and overall survival (OS) of patients treated with this therapy in induction and reinduction to toxicities of similar patients treated on TOT17.

Detailed Description

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Patients will be identified in the first 3 days of therapy during their treatment on INITIALL.

Treatment will consist of 3 main phases: Induction, Early Post Induction \[including Consolidation, High-Dose Methotrexate, Intensification, Interim 1, Reinduction 1, Interim 2, and Reinduction 2\], and Maintenance.

Induction:

* Remission Induction includes 3 days of therapy on the INITIALL classification protocol as well as the remainder of a total of 4 weeks of induction treatment on this trial. Treatment includes a total of 28 days of dexamethasone, 4 weekly doses of vincristine, 3 doses of daunorubicin, 1 dose of Calaspargase pegol, 6 doses of Intrathecal triple therapy (IT MHA), and one of 3 additional drugs. Patients with T-ALL without near-ETP or ETP phenotype (hereafter referred to simply as T-ALL) will receive 25 days of dasatinib. Patients with ETP or near-ETP ALL as well as those with MPAL will receive 14 days of venetoclax. Patients with T-LLy will receive bortezomib. Patients will have a week without chemotherapy at the end of Induction, although patients with Induction failure (MRD ≥5% disease) will proceed directly to consolidation.

Early Post Induction:

* Consolidation will be given following completion of Remission Induction Therapy. Patients will receive 2 cycles of BFM-1b therapy (a single dose of cyclophosphamide at the start of week 1, 4 daily doses of cytarabine in two consecutive weeks, and 2 weeks of mercaptopurine) separated by a week of nelarabine. Patients will have a week without chemotherapy at the end of Consolidation.
* High-dose Methotrexate will be given for 4 cycles to all patients. Patients will also receive an intrathecal chemotherapy treatment with each of the 2-week cycles and will take oral mercaptopurine continuously if tolerated.
* Intensification will be given to patients with T-ALL or ETP/ near-ETP. This therapy includes a week of nelarabine, one week of combination cyclophosphamide and cytarabine, and 1 week of rest without chemotherapy.
* Interim Therapy 1 includes 6 weeks of oral mercaptopurine, 2 weeks (5 days of each week) of dexamethasone, and two doses (weeks 1 and 4) of daunorubicin, vincristine, and calaspargase pegol.
* Reinduction Therapy 1 will consist of 3 weekly doses of vincristine, 1 dose of daunorubicin and calaspargase pegol at the start of the first week, and dexamethasone for 7 days in the first and third weeks. Patients will also receive the same additional agent received during induction based on immunophenotype.
* Interim Therapy 2 includes 6 weeks of oral mercaptopurine, two doses (weeks 1 and 4) of daunorubicin, vincristine, and calaspargase pegol.
* Reinduction Therapy 2 will consist of 3 weekly doses of vincristine, 1 dose of daunorubicin and calaspargase pegol at the start of the first week, and dexamethasone for 7 days in the first and third weeks. Patients will also receive the same additional agent received during induction based on immunophenotype.

Maintenance therapy:

* Early Maintenance Therapy follows Reinduction 2 and lasts 31 weeks. Patients will receive mercaptopurine and methotrexate interrupted by 1 week of nelarabine (week 3), 5 cyclophosphamide/ cytarabine pulses, and every 4-week dexamethasone/ vincristine pulses. For the first 32 weeks, patients will also receive every 4-week pulses including 5 days of dexamethasone and 1 dose of vincristine. Patients will receive low-dose methotrexate in all weeks when they do not receive dexamethasone or vincristine. All patients will receive every 4-week intrathecal chemotherapy beginning 4 weeks after the week of nelarabine.
* Late Maintenance Therapy follows early maintenance and includes daily mercaptopurine, weekly methotrexate, and every 8-week intrathecal chemotherapy. It lasts a total of 44 weeks.

Duration of therapy is approximately 2¼ years. It is recommended that patients be followed every 4 months for 1 year, every 6 months for 1 year and then yearly until the patient is in remission for 10 years and is at least 18 years old.

Conditions

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T-cell Acute Lymphoblastic Leukemia T-cell Lymphoma Mixed Phenotype Acute Leukemia

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Patients with T-ALL (except ETP or near-ETP)

All eligible patients receive intervention according to the Detailed Description section with the following:

Induction: Dexamethasone, Vincristine, Daunorubicin, Calaspargase pegol, Dasatinib, IT MHA

Early Post Induction: Cyclophosphamide, Cytarabine, Mercaptopurine, Nelarabine, IT MHA, Methotrexate, Dasatinib, Dexamethasone, Vincristine, Daunorubicin, Calaspargase pegol

Maintenance: Mercaptopurine, Methotrexate, Nelarabine, Cyclophosphamide, Cytarabine, Dexamethasone, Vincristine, Dasatinib, IT MHA, Thioguanine

Group Type EXPERIMENTAL

Dexamethasone

Intervention Type DRUG

Given orally (PO) or intravenously (IV).

Vincristine

Intervention Type DRUG

Given IV.

Daunorubicin

Intervention Type DRUG

Given IV.

Calaspargase pegol

Intervention Type DRUG

Given IV.

Dasatinib

Intervention Type DRUG

Given PO

Intrathecal triple therapy (methotrexate + hydrocortisone + cytarabine)

Intervention Type DRUG

Given Intrathecal (IT), Age adjusted.

Cyclophosphamide

Intervention Type DRUG

Given IV.

Cytarabine

Intervention Type DRUG

Given IV or IT.

Mercaptopurine

Intervention Type DRUG

Given PO.

Nelarabine

Intervention Type DRUG

Given IV

Methotrexate

Intervention Type DRUG

Given IT, IV, PO or intramuscular (IM).

Thioguanine

Intervention Type DRUG

Given PO (participants intolerant to mercaptopurine).

Patients with ETP or near-ETP ALL or MPAL

All eligible patients receive intervention according to the Detailed Description section with the following:

Induction: Dexamethasone, Vincristine, Daunorubicin, Calaspargase pegol, Venetoclax, IT MHA

Early Post Induction: Cyclophosphamide, Cytarabine, Mercaptopurine, Nelarabine, IT MHA, Methotrexate, Dexamethasone, Vincristine, Daunorubicin, Calaspargase pegol, Venetoclax

Maintenance: Mercaptopurine, Methotrexate, Nelarabine, Cyclophosphamide, Cytarabine, Dexamethasone, Vincristine, IT MHA, Thioguanine

Group Type EXPERIMENTAL

Dexamethasone

Intervention Type DRUG

Given orally (PO) or intravenously (IV).

Vincristine

Intervention Type DRUG

Given IV.

Daunorubicin

Intervention Type DRUG

Given IV.

Calaspargase pegol

Intervention Type DRUG

Given IV.

Venetoclax

Intervention Type DRUG

Given PO (ETP, near-ETP, and MPAL only).

Intrathecal triple therapy (methotrexate + hydrocortisone + cytarabine)

Intervention Type DRUG

Given Intrathecal (IT), Age adjusted.

Cyclophosphamide

Intervention Type DRUG

Given IV.

Cytarabine

Intervention Type DRUG

Given IV or IT.

Mercaptopurine

Intervention Type DRUG

Given PO.

Nelarabine

Intervention Type DRUG

Given IV

Methotrexate

Intervention Type DRUG

Given IT, IV, PO or intramuscular (IM).

Thioguanine

Intervention Type DRUG

Given PO (participants intolerant to mercaptopurine).

Patients with T-LLy

All eligible patients receive intervention according to the Detailed Description section with the following:

Induction: Dexamethasone, Vincristine, Daunorubicin, Calaspargase pegol, Bortezomib, IT MHA

Early Post Induction: Cyclophosphamide, Cytarabine, Mercaptopurine, IT MHA, Methotrexate, Dexamethasone, Vincristine, Daunorubicin, Calaspargase pegol, Bortezomib

Maintenance: Mercaptopurine, Methotrexate, Cyclophosphamide, Cytarabine, Dexamethasone, Vincristine, IT MHA, Thioguanine

Group Type EXPERIMENTAL

Dexamethasone

Intervention Type DRUG

Given orally (PO) or intravenously (IV).

Vincristine

Intervention Type DRUG

Given IV.

Daunorubicin

Intervention Type DRUG

Given IV.

Calaspargase pegol

Intervention Type DRUG

Given IV.

Bortezomib

Intervention Type DRUG

Given IV (T-LLy only).

Intrathecal triple therapy (methotrexate + hydrocortisone + cytarabine)

Intervention Type DRUG

Given Intrathecal (IT), Age adjusted.

Cyclophosphamide

Intervention Type DRUG

Given IV.

Cytarabine

Intervention Type DRUG

Given IV or IT.

Mercaptopurine

Intervention Type DRUG

Given PO.

Methotrexate

Intervention Type DRUG

Given IT, IV, PO or intramuscular (IM).

Thioguanine

Intervention Type DRUG

Given PO (participants intolerant to mercaptopurine).

Interventions

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Dexamethasone

Given orally (PO) or intravenously (IV).

Intervention Type DRUG

Vincristine

Given IV.

Intervention Type DRUG

Daunorubicin

Given IV.

Intervention Type DRUG

Calaspargase pegol

Given IV.

Intervention Type DRUG

Dasatinib

Given PO

Intervention Type DRUG

Venetoclax

Given PO (ETP, near-ETP, and MPAL only).

Intervention Type DRUG

Bortezomib

Given IV (T-LLy only).

Intervention Type DRUG

Intrathecal triple therapy (methotrexate + hydrocortisone + cytarabine)

Given Intrathecal (IT), Age adjusted.

Intervention Type DRUG

Cyclophosphamide

Given IV.

Intervention Type DRUG

Cytarabine

Given IV or IT.

Intervention Type DRUG

Mercaptopurine

Given PO.

Intervention Type DRUG

Nelarabine

Given IV

Intervention Type DRUG

Methotrexate

Given IT, IV, PO or intramuscular (IM).

Intervention Type DRUG

Thioguanine

Given PO (participants intolerant to mercaptopurine).

Intervention Type DRUG

Other Intervention Names

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Decadron Hexadrol® Vincristine Sulfate Oncovin Daunomycin ASPARLAS Sprycel® Venclexta® Velcade® IT MHA Cytoxan® Ara-C Cytosine arabinoside 6-MP Arranon Atriance Trexall® 6-thioguanine Tabloid®

Eligibility Criteria

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Inclusion Criteria

* Enrollment on INITIALL.
* Age 1-18.99 years at the time of enrollment on INITIALL.
* T-Acute lymphoblastic leukemia or lymphoblastic lymphoma or mixed phenotype acute leukemia/ lymphoma
* No prior chemotherapy excluding therapy given on or allowed by INITIALL.
* Patient has completed no more than 3 days of chemotherapy on INITIALL.
* Direct bilirubin ≤ 1.5x the upper limit of normal for age
* Alanine aminotransferase (ALT) ≤ 5x the upper limit of normal for age
* 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), 0.6 (Female)
* Age: 2 to \< 6 years - Maximum serum creatinine (mg/dL): 0.8 (Male), 0.8 (Female)
* Age: 6 to \< 10 years - Maximum serum creatinine (mg/dL): 1 (Male), 1 (Female)
* Age: 10 to \< 13 years - Maximum serum creatinine (mg/dL): 1.2 (Male), 1.2 (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)

Exclusion Criteria

* Inability or unwillingness to give informed consent/ assent as applicable.
* Patients with \> Grade 2 neuropathy at the time of enrollment (participant with T-LLy only).
* Documented malabsorption syndrome or any other condition that precludes receipt of oral medications.
* Known HIV infection or active hepatitis B (defined as hepatitis B surface antigen-positive) or C (defined as hepatitis C antibody-positive).
* Pregnant or lactating.
* For patients of reproductive potential, unwillingness to use highly effective contraception for the duration of protocol therapy and for 90 days afterwards.
* Receipt of a strong or moderate CYP3A4 inducer such as rifampin, carbamazepine, phenytoin, and St. John's wort within 7 days of the start of protocol treatment.
* Consumption of grapefruit, grapefruit products, Seville oranges, or starfruit within 3 days of the start of protocol therapy.
Minimum Eligible Age

1 Year

Maximum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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AbbVie

INDUSTRY

Sponsor Role collaborator

St. Jude Children's Research Hospital

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Seth E. Karol, MD, MSCI

Role: PRINCIPAL_INVESTIGATOR

St. Jude Children's Research Hospital

Locations

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Rady Children's Hospital

San Diego, California, United States

Site Status RECRUITING

Saint Francis Children's Hospital

Tulsa, Oklahoma, United States

Site Status RECRUITING

St. Jude Children's Research Hospital

Memphis, Tennessee, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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Seth E. Karol, MD, MSCI

Role: CONTACT

866-278-5833

Facility Contacts

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Victor Wong, MD

Role: primary

858-966-5811

Ashraf Mohamed, MD

Role: primary

918-502-6720

Seth E. Karol, MD, MSCI

Role: primary

866-278-5833

Related Links

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http://www.stjude.org

St. Jude Children's Research Hospital

http://www.stjude.org/protocols

Clinical Trials Open at St. Jude

Other Identifiers

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NCI-2024-03015

Identifier Type: REGISTRY

Identifier Source: secondary_id

SJALL23T

Identifier Type: -

Identifier Source: org_study_id

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