Trial Title:
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
Condition:
T-cell Acute Lymphoblastic Leukemia
T-cell Lymphoma
Mixed Phenotype Acute Leukemia
Conditions: Official terms:
Lymphoma
Leukemia
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Lymphoid
Lymphoma, T-Cell
Lymphoma, T-Cell, Peripheral
Precursor T-Cell Lymphoblastic Leukemia-Lymphoma
Acute Disease
Cytarabine
Dexamethasone
Hydrocortisone
Cyclophosphamide
Methotrexate
Vincristine
Bortezomib
Venetoclax
Daunorubicin
Dasatinib
Mercaptopurine
Thioguanine
Conditions: Keywords:
Newly Diagnosed
Children
Young Adults
T-cell Acute Lymphoblastic Leukemia
T-cell Lymphoma
Mixed Phenotype Acute Leukemia (MPAL)
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Not yet recruiting
Study design:
Allocation:
Non-Randomized
Intervention model:
Parallel Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Dexamethasone
Description:
Given orally (PO) or intravenously (IV).
Arm group label:
Patients with ETP or near-ETP ALL or MPAL
Arm group label:
Patients with T-ALL (except ETP or near-ETP)
Arm group label:
Patients with T-LLy
Other name:
Decadron
Other name:
Hexadrol®
Intervention type:
Drug
Intervention name:
Vincristine
Description:
Given IV.
Arm group label:
Patients with ETP or near-ETP ALL or MPAL
Arm group label:
Patients with T-ALL (except ETP or near-ETP)
Arm group label:
Patients with T-LLy
Other name:
Vincristine Sulfate
Other name:
Oncovin
Intervention type:
Drug
Intervention name:
Daunorubicin
Description:
Given IV.
Arm group label:
Patients with ETP or near-ETP ALL or MPAL
Arm group label:
Patients with T-ALL (except ETP or near-ETP)
Arm group label:
Patients with T-LLy
Other name:
Daunomycin
Intervention type:
Drug
Intervention name:
Calaspargase pegol
Description:
Given IV.
Arm group label:
Patients with ETP or near-ETP ALL or MPAL
Arm group label:
Patients with T-ALL (except ETP or near-ETP)
Arm group label:
Patients with T-LLy
Other name:
ASPARLAS
Intervention type:
Drug
Intervention name:
Dasatinib
Description:
Given PO
Arm group label:
Patients with T-ALL (except ETP or near-ETP)
Other name:
Sprycel®
Intervention type:
Drug
Intervention name:
Venetoclax
Description:
Given PO (ETP, near-ETP, and MPAL only).
Arm group label:
Patients with ETP or near-ETP ALL or MPAL
Other name:
Venclexta®
Intervention type:
Drug
Intervention name:
Bortezomib
Description:
Given IV (T-LLy only).
Arm group label:
Patients with T-LLy
Other name:
Velcade®
Intervention type:
Drug
Intervention name:
Intrathecal triple therapy (methotrexate + hydrocortisone + cytarabine)
Description:
Given Intrathecal (IT), Age adjusted.
Arm group label:
Patients with ETP or near-ETP ALL or MPAL
Arm group label:
Patients with T-ALL (except ETP or near-ETP)
Arm group label:
Patients with T-LLy
Other name:
IT MHA
Intervention type:
Drug
Intervention name:
Cyclophosphamide
Description:
Given IV.
Arm group label:
Patients with ETP or near-ETP ALL or MPAL
Arm group label:
Patients with T-ALL (except ETP or near-ETP)
Arm group label:
Patients with T-LLy
Other name:
Cytoxan®
Intervention type:
Drug
Intervention name:
Cytarabine
Description:
Given IV or IT.
Arm group label:
Patients with ETP or near-ETP ALL or MPAL
Arm group label:
Patients with T-ALL (except ETP or near-ETP)
Arm group label:
Patients with T-LLy
Other name:
Ara-C
Other name:
Cytosine arabinoside
Intervention type:
Drug
Intervention name:
Mercaptopurine
Description:
Given PO.
Arm group label:
Patients with ETP or near-ETP ALL or MPAL
Arm group label:
Patients with T-ALL (except ETP or near-ETP)
Arm group label:
Patients with T-LLy
Other name:
6-MP
Intervention type:
Drug
Intervention name:
Nelarabine
Description:
Given IV
Arm group label:
Patients with ETP or near-ETP ALL or MPAL
Arm group label:
Patients with T-ALL (except ETP or near-ETP)
Other name:
Arranon
Other name:
Atriance
Intervention type:
Drug
Intervention name:
Methotrexate
Description:
Given IT, IV, PO or intramuscular (IM).
Arm group label:
Patients with ETP or near-ETP ALL or MPAL
Arm group label:
Patients with T-ALL (except ETP or near-ETP)
Arm group label:
Patients with T-LLy
Other name:
Trexall®
Intervention type:
Drug
Intervention name:
Thioguanine
Description:
Given PO (participants intolerant to mercaptopurine).
Arm group label:
Patients with ETP or near-ETP ALL or MPAL
Arm group label:
Patients with T-ALL (except ETP or near-ETP)
Arm group label:
Patients with T-LLy
Other name:
6-thioguanine
Other name:
Tabloid®
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.
Detailed 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.
Criteria for 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.
Gender:
All
Minimum age:
1 Year
Maximum age:
18 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
St. Jude Children's Research Hospital
Address:
City:
Memphis
Zip:
38105
Country:
United States
Contact:
Last name:
Seth E. Karol, MD, MSCI
Phone:
866-278-5833
Email:
referralinfo@stjude.org
Investigator:
Last name:
Seth E. Karol, MD, MSCI
Email:
Principal Investigator
Start date:
December 2024
Completion date:
December 2033
Lead sponsor:
Agency:
St. Jude Children's Research Hospital
Agency class:
Other
Collaborator:
Agency:
AbbVie
Agency class:
Industry
Source:
St. Jude Children's Research Hospital
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06390319
http://www.stjude.org
http://www.stjude.org/protocols
