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)

T-cell Lymphoma Clinical Trial

Official title:

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)

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06390319
• Other study ID #: SJALL23T
• Secondary ID: NCI-2024-03015
• Status: Not yet recruiting
• Phase: Phase 2
• Start date: July 2024
• Est. completion date: December 2033

Study information

• Verified date: June 2024
• Source: St. Jude Children's Research Hospital
• Contact: Seth E. Karol, MD, MSCI
• Phone: 866-278-5833
• Email: referralinfo[@]stjude.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 145
• Est. completion date: December 2033
• Est. primary completion date: December 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 1 Year to 18 Years

Eligibility

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.

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.

• For patients with ETP ALL, near-ETP ALL, and MPAL: consumption of grapefruit, grapefruit products, Seville oranges, or starfruit within 3 days of the start of protocol therapy.

Related Conditions & MeSH terms

• Acute Disease
• Leukemia
• Leukemia, Lymphoid
• Lymphoma
• Lymphoma, T-Cell
• Lymphoma, T-Cell, Peripheral
• Mixed Phenotype Acute Leukemia
• Precursor Cell Lymphoblastic Leukemia-Lymphoma
• Precursor T-Cell Lymphoblastic Leukemia-Lymphoma
• T-cell Acute Lymphoblastic Leukemia
• T-cell Lymphoma

Intervention

Drug:
• Dexamethasone
Given orally (PO) or intravenously (IV).
• Vincristine
Given IV.
• Daunorubicin
Given IV.
• Calaspargase pegol
Given IV.
• Dasatinib
Given PO
• Venetoclax
Given PO (ETP, near-ETP, and MPAL only).
• Bortezomib
Given IV (T-LLy only).
• Intrathecal triple therapy (methotrexate + hydrocortisone + cytarabine)
Given Intrathecal (IT), Age adjusted.
• Cyclophosphamide
Given IV.
• Cytarabine
Given IV or IT.
• Mercaptopurine
Given PO.
• Nelarabine
Given IV
• Methotrexate
Given IT, IV, PO or intramuscular (IM).
• Thioguanine
Given PO (participants intolerant to mercaptopurine).

Locations

Country	Name	City	State
United States	St. Jude Children's Research Hospital	Memphis	Tennessee

Sponsors (2)

Lead Sponsor	Collaborator
St. Jude Children's Research Hospital	AbbVie

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	Event-free survival (EFS)	Kaplan-Meier estimates for EFS will be calculated along with standard error.	Up to 10 years
Secondary	Overall survival (OS)	Kaplan-Meier estimates for OS will be calculated along with standard error.	Up to 10 years
Secondary	Incidence of grade 4 toxicities	Adverse events will be graded using Common Terminology Criteria for Adverse Events version 5 and compared using Fisher's or exact Chi-square test.	Up to 30 days after last dose of study treatment
Secondary	EFS compared to Total 17 (TOT17-NCT03117751)	Comparisons of EFS to the corresponding TOT17 will be performed by the log-rank test.	Up to 10 years
Secondary	OS compared to TOT17	Comparisons of OS to the corresponding TOT17 will be performed by the log-rank test.	Up to 10 years

External Links

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