Improving treatment responses in children with T-cell leukemia or lymphoma

SJALL23T: 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)

This study is testing if adding two new drugs to standard chemotherapy can help children and young adults with T-cell leukemia or lymphoma have better treatment outcomes.

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 100 (estimated)
• Ages: 1 Year to 18 Years
• Sex: All
• Sponsor: St. Jude Children's Research Hospital (other)
• Drugs / interventions: chemotherapy, dasatinib, Methotrexate, cyclophosphamide
• Locations: 3 sites (San Diego, California and 2 other locations)
• Trial ID: NCT06390319 on ClinicalTrials.gov

What this trial studies

This clinical trial evaluates the effectiveness of adding dasatinib or venetoclax to standard chemotherapy for children and young adults newly diagnosed with T-cell acute lymphoblastic leukemia, T-cell lymphoma, or mixed phenotype acute leukemia. The study aims to determine if these additional agents can increase the rate of minimal residual disease (MRD) negativity at the end of induction therapy compared to standard treatment. Participants will undergo a structured treatment regimen that includes multiple phases of chemotherapy, with specific drugs assigned based on their leukemia subtype. The trial will also assess overall survival and event-free survival rates, as well as the toxicity of the treatments.

Who should consider this trial

Good fit: Ideal candidates are children and young adults aged 1 to 18.99 years with newly diagnosed T-cell acute lymphoblastic leukemia, T-cell lymphoma, or mixed phenotype acute leukemia.

Not a fit: Patients who have received prior chemotherapy or those with significant liver or kidney dysfunction may not benefit from this study.

Why it matters

Potential benefit: If successful, this trial could lead to improved treatment outcomes and survival rates for children with aggressive forms of leukemia and lymphoma.

How similar studies have performed: Other studies have shown promise with similar approaches, but this specific combination of treatments is being evaluated for the first time in this patient population.

Eligibility criteria

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.

Where this trial is running

San Diego, California and 2 other locations

• Rady Children's Hospital — San Diego, California, United States (RECRUITING)
• Saint Francis Children's Hospital — Tulsa, Oklahoma, United States (RECRUITING)
• St. Jude Children's Research Hospital — Memphis, Tennessee, United States (RECRUITING)

Study contacts

• Principal investigator: Seth E. Karol, MD, MSCI — St. Jude Children's Research Hospital
• Study coordinator: Seth E. Karol, MD, MSCI

Conditions: T-cell Acute Lymphoblastic Leukemia, T-cell Lymphoma, Mixed Phenotype Acute Leukemia, Newly Diagnosed, Children, Young Adults