Trial Title:
Therapy for Newly Diagnosed Patients With B-Cell Precursor Acute Lymphoblastic Leukemia and Lymphoma
NCT ID:
NCT06533748
Condition:
Acute Lymphoblastic Leukemia
Lymphoblastic Lymphoma
Conditions: Official terms:
Lymphoma
Leukemia
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Lymphoid
Cytarabine
Dexamethasone
Hydrocortisone
Cyclophosphamide
Methotrexate
Vincristine
Daunorubicin
Dasatinib
Mercaptopurine
Thioguanine
Blinatumomab
Inotuzumab Ozogamicin
Conditions: Keywords:
Acute Lymphoblastic Leukemia
Lymphoblastic Lymphoma
Newly Diagnosed
Antigen-directed therapies
Induction therapy
Children
Young Adults
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Not yet recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Intervention model description:
This study utilizes a single arm phase II design enrolling eligible participants with
newly diagnosed B-cell precursor acute lymphoblastic leukemia and lymphoma.
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Dexamethasone
Description:
Given orally (PO) or intravenously (IV).
Arm group label:
SJALL23H Treated Patients
Other name:
Decadron
Other name:
Hexadrol®
Intervention type:
Drug
Intervention name:
Vincristine
Description:
Given IV.
Arm group label:
SJALL23H Treated Patients
Other name:
Vincristine Sulfate
Other name:
Oncovin
Intervention type:
Drug
Intervention name:
Inotuzumab
Description:
Given IV.
Arm group label:
SJALL23H Treated Patients
Other name:
Inotuzumab ozogamicin
Other name:
BESPONSA®
Intervention type:
Drug
Intervention name:
Blinatumomab
Description:
Given IV.
Arm group label:
SJALL23H Treated Patients
Other name:
BLINCYTO®
Intervention type:
Drug
Intervention name:
Dasatinib
Description:
Given PO.
Arm group label:
SJALL23H Treated Patients
Other name:
Sprycel®
Intervention type:
Procedure
Intervention name:
IT MHA
Description:
Given Intrathecal (IT), Age adjusted.
Arm group label:
SJALL23H Treated Patients
Other name:
Intrathecal triple therapy (methotrexate + hydrocortisone + cytarabine)
Intervention type:
Drug
Intervention name:
Cyclophosphamide
Description:
Given IV.
Arm group label:
SJALL23H Treated Patients
Other name:
Cytoxan®
Intervention type:
Drug
Intervention name:
Cytarabine
Description:
Given IV or IT.
Arm group label:
SJALL23H Treated Patients
Other name:
Cytosine arabinoside
Other name:
Ara-C
Intervention type:
Drug
Intervention name:
Methotrexate
Description:
Given IT, IV, PO or intramuscular (IM).
Arm group label:
SJALL23H Treated Patients
Other name:
MTX
Other name:
Trexall®
Intervention type:
Drug
Intervention name:
6-Mercaptopurine
Description:
Given PO.
Arm group label:
SJALL23H Treated Patients
Other name:
Mercaptopurine
Other name:
6-MP
Intervention type:
Drug
Intervention name:
Calaspargase
Description:
Given IV.
Arm group label:
SJALL23H Treated Patients
Other name:
ASPARLAS
Intervention type:
Drug
Intervention name:
Daunorubicin
Description:
Given IV.
Arm group label:
SJALL23H Treated Patients
Other name:
Daunomycin
Intervention type:
Drug
Intervention name:
Thioguanine
Description:
Given PO (participants intolerant to mercaptopurine).
Arm group label:
SJALL23H Treated Patients
Other name:
6-thioguanine
Other name:
Tabloid®
Summary:
This is a Phase II clinical trial testing the use of two antigen-directed therapies,
inotuzumab and blinatumomab, as part of induction therapy for children and young adults
with newly diagnosed B-cell precursor acute lymphoblastic leukemia and lymphoma.
Primary Objective
- To assess if the flow-cytometry assessed MRD-negative remission rate following an
immunotherapy-based Induction in NCI-high risk patients without favorable genetic
features is higher than the results of similar patients treated on AALL1131.
Secondary Objectives
- To compare flow-cytometry assessed MRD-negative rates at the end of Induction for
patients treated with this therapy compared to similar patients treated on TOT17.
- To compare the rate of significant toxicities in patients treated with this therapy
to those treated with standard-risk therapy on TOT17.
- To assess the event free and overall survival of patients treated with this therapy.
Detailed description:
This study utilizes a single arm phase II design. Treatment will consist of 3 main
phases: Induction, early post induction [including Consolidation, Blinatumomab 1,
High-Dose Methotrexate, Reinduction, Interim, Reconsolidation, and Blinatumomab 2], and
Maintenance.
Induction:
- Induction includes 7 days of therapy on the INITIALL classification protocol
(NCT06289673) as well as 5 further weeks of treatment on this trial. Treatment
includes 15 days of oral (PO) or intravenous (IV) dexamethasone, 3 weekly doses of
vincristine IV, and 2 doses of inotuzumab IV on Days 2 and 8. Patients will then
receive blinatumomab IV from Days 9-36. Dasatinib PO will be added beginning on Day
12 for patients with an ABL-class fusion including patients with Ph+ ALL. These
patients will also receive dasatinib in all subsequent cycles of therapy.
Intrathecal (IT) MHA will be given. 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 receive cyclophosphamide intravenous (IV), cytarabine IV, inotuzumab IV,
and dasatinib PO for patients with ABL-class fusion. Patients will have a week
without chemotherapy at the end of Consolidation.
- Blinatumomab 1 will be given for four weeks to all patients after recovery from
Consolidation.
- High-dose Methotrexate will be given IV every two weeks for four cycles. Patients
will also receive an intrathecal chemotherapy treatment with each of the 2 week
cycles and will take oral mercaptopurine continuously if tolerated.
- Reinduction will consist of dexamethasone for 7 days in the first and third week, 3
weekly doses of vincristine IV, 1 dose of daunorubicin IV, 1 dose of calaspargase
IV, intrathecal (IT) MHA one dose, and dasatinib PO daily (for patients with
ABL-class fusion).
- Interim includes mercaptopurine po daily for 6 weeks, dexamethasone for 1 week (5
days), daunorubicin and vincristine IV on day 1 of weeks 2 and 5, calaspargase IV on
day 1 of weeks 1 and 4, IT MHA on day 1 of week 4 and dasatinib po daily for 6 weeks
(for patients with ABL-class fusion). Patients will have a week without chemotherapy
at the end of Interim Therapy. Patients with Down syndrome will not receive
daunorubicin during this phase.
- Reconsolidation will repeat therapy given in Consolidation but replace the
investigational inotuzumab with traditional mercaptopurine.
- Blinatumomab 2 will be given for four weeks to patients with elevated end of
induction MRD and patients with Down syndrome after Reconsolidation.
Maintenance therapy follows Reconsolidation or Blinatumomab 2 (for those patients
receiving this therapy) and includes 8 pulses of dexamethasone and vincristine given
every 4 weeks, weekly methotrexate, daily mercaptopurine, intrathecal therapy, and
dasatinib (for patients with ABL-class fusions). Maintenance therapy lasts a total of 80
weeks.
Duration of therapy is approximately 2¼ years. Follow-up is recommended 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.
- B-Acute lymphoblastic leukemia or lymphoblastic lymphoma.
- No prior chemotherapy excluding therapy given on or allowed by INITIALL.
- NCI high-risk (age 10 years or greater or presenting WBC count ≥50,000 cells/microL)
or NCI standard-risk and a HR clinical feature as listed below:
- CNS3 disease (≥5 WBC/microL CSF with blasts present)
- Testicular involvement of leukemia
- Steroid pretreatment defined as >24 hours of therapy in the 14 days prior to
enrollment on INITIALL if a preceding WBC to define NCI risk is unavailable
- For lymphoblastic lymphoma, Stage 3-4 disease OR Stage 1-2 disease in patient ages
≥10 years OR HR clinical feature as defined above.
- Adequate liver function defined as:
- Direct bilirubin ≤ 1.5x the upper limit of normal for age and alanine
transaminase (ALT) ≤ 5x the upper limit of normal for age.
- Patients with ALT or aspartate transferase (AST) 2.5-5x the upper limit of
normal for age are ineligible unless the increase is attributable to hemolysis.
- Adequate renal function defined as:
- 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 and
female)
- Age: 2 to <6 years; maximum serum creatinine (mg/dL): 0.8 (male and
female)
- Age: 6 to <10 years; maximum serum creatinine (mg/dL): 1.0 (male and
female)
- Age: 10 to <13 years; maximum serum creatinine (mg/dL): 1.2 (male and
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)
- Eligibility for inclusion post-induction requires meeting the first 4 Inclusion
criteria above AND:
- Treatment on SJALL23H for Induction OR
- Lymphoblastic lymphoma, initially treated on an SJALL protocol OR standard
(non-protocol) therapy, without a complete response at the end of induction OR
- NCI-SR ALL at diagnosis and treated with an SJALL protocol OR standard
(non-protocol) therapy who have
- Slow response to therapy (≥0.1% MRD at end of induction for patients with
hyperdiploid ALL or ≥0.01% MRD at end of induction for others with ALL) OR
- HR genetics as defined in the protocol.
Exclusion Criteria:
- Presence of ETV6::RUNX1 fusion unless also having a HR clinical feature OR slow
response to induction therapy.
- History or presence of clinically relevant central nervous system (CNS) pathology or
event such as epilepsy, childhood or adult non-febrile seizure, paresis, aphasia,
stroke, severe brain injuries, dementia, Parkinson's disease, cerebellar disease,
organic brain syndrome, or psychosis. History of simple febrile seizure during
childhood and presence of CNS leukemia at diagnosis are not exclusions to
participation.
- Active uncontrolled infection.
- Current active autoimmune disease or history of autoimmune disease with the
potential for CNS involvement.
- History of venoocclusive disease/ sinusoidal obstructive syndrome.
- Unstable cardiac disease including QTc >500msec.
- Inability or unwillingness to give informed consent/ assent as applicable.
- Pregnant or lactating.
- For patients of reproductive potential, unwillingness to use effective contraception
for the duration 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:
May 2034
Lead sponsor:
Agency:
St. Jude Children's Research Hospital
Agency class:
Other
Collaborator:
Agency:
Pfizer
Agency class:
Industry
Collaborator:
Agency:
Amgen
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/NCT06533748
http://www.stjude.org
http://www.stjude.org/protocols
