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)

NCT06390319 | Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: SJALL23TNCI-2024-03015
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 3

Brief Summary

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.

Conditions

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

Keywords

Newly Diagnosed; Children; Young Adults; T-cell Acute Lymphoblastic Leukemia; T-cell Lymphoma; Mixed Phenotype Acute Leukemia (MPAL)

Outcome Measures

Primary Outcomes (2)

• Minimal residual disease (MRD)-negativity rate in patients with T cell acute lymphoblastic leukemia

  Comparison of the probability of achieving negative MRD (\<0.01%) and M1 bone marrow status at the end of induction between this protocol and COG AALL1231 will be performed. Statistical analysis of the primary objective will be conducted according to a group sequential design with 1 interim analysis, by a slightly modified version of the procedure for binary endpoint.

  Up to end of induction day 29 or death

• MRD-negativity rate in patients with ETP or near ETP ALL

  The proportion of patients with ETP or near-ETP treated with venetoclax based induction will be compared to the rate of such unsuccessful induction in patients treated on AALL1231 with a standard 4-drug induction. The probability of achieving negative MRD will be tested using a one-sided exact binomial proportion test.

  Up to end of induction day 29 or death

Secondary Outcomes (5)

• Event-free survival (EFS)

  Up to 10 years

• Overall survival (OS)

  Up to 10 years

• Incidence of grade 4 toxicities

  Up to 30 days after last dose of study treatment

• EFS compared to Total 17 (TOT17-NCT03117751)

  Up to 10 years

• OS compared to TOT17

  Up to 10 years

Study Arms (3)

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

EXPERIMENTAL

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

Drug: Dexamethasone; Drug: Vincristine; Drug: Daunorubicin; Drug: Calaspargase pegol; Drug: Dasatinib; Drug: Intrathecal triple therapy (methotrexate + hydrocortisone + cytarabine); Drug: Cyclophosphamide; Drug: Cytarabine; Drug: Mercaptopurine; Drug: Nelarabine; Drug: Methotrexate; Drug: Thioguanine

Patients with ETP or near-ETP ALL or MPAL

EXPERIMENTAL

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

Drug: Dexamethasone; Drug: Vincristine; Drug: Daunorubicin; Drug: Calaspargase pegol; Drug: Venetoclax; Drug: Intrathecal triple therapy (methotrexate + hydrocortisone + cytarabine); Drug: Cyclophosphamide; Drug: Cytarabine; Drug: Mercaptopurine; Drug: Nelarabine; Drug: Methotrexate; Drug: Thioguanine

Patients with T-LLy

EXPERIMENTAL

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

Drug: Dexamethasone; Drug: Vincristine; Drug: Daunorubicin; Drug: Calaspargase pegol; Drug: Bortezomib; Drug: Intrathecal triple therapy (methotrexate + hydrocortisone + cytarabine); Drug: Cyclophosphamide; Drug: Cytarabine; Drug: Mercaptopurine; Drug: Methotrexate; Drug: Thioguanine

Interventions

Dexamethasone DRUG

Given orally (PO) or intravenously (IV).

Also known as: Decadron, Hexadrol®

Patients with ETP or near-ETP ALL or MPAL; Patients with T-ALL (except ETP or near-ETP); Patients with T-LLy

Vincristine DRUG

Given IV.

Also known as: Vincristine Sulfate, Oncovin

Patients with ETP or near-ETP ALL or MPAL; Patients with T-ALL (except ETP or near-ETP); Patients with T-LLy

Daunorubicin DRUG

Given IV.

Also known as: Daunomycin

Patients with ETP or near-ETP ALL or MPAL; Patients with T-ALL (except ETP or near-ETP); Patients with T-LLy

Calaspargase pegol DRUG

Given IV.

Also known as: ASPARLAS

Patients with ETP or near-ETP ALL or MPAL; Patients with T-ALL (except ETP or near-ETP); Patients with T-LLy

Dasatinib DRUG

Given PO

Also known as: Sprycel®

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

Venetoclax DRUG

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

Also known as: Venclexta®

Patients with ETP or near-ETP ALL or MPAL

Bortezomib DRUG

Given IV (T-LLy only).

Also known as: Velcade®

Patients with T-LLy

Intrathecal triple therapy (methotrexate + hydrocortisone + cytarabine) DRUG

Given Intrathecal (IT), Age adjusted.

Also known as: IT MHA

Patients with ETP or near-ETP ALL or MPAL; Patients with T-ALL (except ETP or near-ETP); Patients with T-LLy

Cyclophosphamide DRUG

Given IV.

Also known as: Cytoxan®

Patients with ETP or near-ETP ALL or MPAL; Patients with T-ALL (except ETP or near-ETP); Patients with T-LLy

Cytarabine DRUG

Given IV or IT.

Also known as: Ara-C, Cytosine arabinoside

Patients with ETP or near-ETP ALL or MPAL; Patients with T-ALL (except ETP or near-ETP); Patients with T-LLy

Mercaptopurine DRUG

Given PO.

Also known as: 6-MP

Patients with ETP or near-ETP ALL or MPAL; Patients with T-ALL (except ETP or near-ETP); Patients with T-LLy

Nelarabine DRUG

Given IV

Also known as: Arranon, Atriance

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

Methotrexate DRUG

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

Also known as: Trexall®

Patients with ETP or near-ETP ALL or MPAL; Patients with T-ALL (except ETP or near-ETP); Patients with T-LLy

Thioguanine DRUG

Given PO (participants intolerant to mercaptopurine).

Also known as: 6-thioguanine, Tabloid®

Patients with ETP or near-ETP ALL or MPAL; Patients with T-ALL (except ETP or near-ETP); Patients with T-LLy

Eligibility Criteria

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

You may qualify if:

• 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)

You may not qualify if:

• 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.

Sponsors & Collaborators

• AbbVie: collaborator
• St. Jude Children's Research Hospital: lead

Study Sites (3)

Rady Children's Hospital

San Diego, California, 92123, United States

RECRUITING

Saint Francis Children's Hospital

Tulsa, Oklahoma, 74136, United States

RECRUITING

St. Jude Children's Research Hospital

Memphis, Tennessee, 38105, United States

RECRUITING

Related Links

• St. Jude Children's Research Hospital
• Clinical Trials Open at St. Jude

MeSH Terms

Conditions

Precursor T-Cell Lymphoblastic Leukemia-Lymphoma; Lymphoma, T-Cell; Leukemia, Biphenotypic, Acute

Interventions

Dexamethasone; Calcium Dobesilate; Vincristine; Daunorubicin; calaspargase pegol; Dasatinib; venetoclax; Bortezomib; Methotrexate; Hydrocortisone; Cytarabine; Cyclophosphamide; Mercaptopurine; nelarabine; Thioguanine

Condition Hierarchy (Ancestors)

Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Lymphoma, Non-Hodgkin; Lymphoma

Intervention Hierarchy (Ancestors)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Benzenesulfonates; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Arylsulfonates; Arylsulfonic Acids; Sulfonic Acids; Sulfur Acids; Sulfur Compounds; 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; Aminoglycosides; Glycosides; Carbohydrates; Thiazoles; Azoles; Heterocyclic Compounds, 1-Ring; Pyrimidines; Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Pyrazines; Aminopterin; Pterins; Pteridines; Pregnenediones; Pregnenes; 11-Hydroxycorticosteroids; Hydroxycorticosteroids; Adrenal Cortex Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; 17-Hydroxycorticosteroids; Cytidine; Pyrimidine Nucleosides; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Sulfhydryl Compounds; Purines

Study Officials

• Seth E. Karol, MD, MSCI

  St. Jude Children's Research Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Seth E. Karol, MD, MSCI

CONTACT

888-226-4343; referralinfo@stjude.org

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 25, 2024
• First Posted: April 30, 2024
• Study Start: December 27, 2024
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2033
• Last Updated: May 1, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Data will be made available at the time of article publication.
• Access Criteria: Data will be provided to researchers following a formal request with the following information: full name of requestor, affiliation, data set requested, and timing of when data is needed. As an informational point, the lead statistician and study principal investigator will be informed that primary results datasets have been requested.

Locations

US (3)