Therapy for Newly Diagnosed Patients With B-Cell Precursor Acute Lymphoblastic Leukemia and Lymphoma
About this study
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.
- Condition
- Acute Lymphoblastic Leukemia, Lymphoblastic Lymphoma
- Tested
- Dexamethasone, Vincristine, Inotuzumab, Blinatumomab, Dasatinib, IT MHA, Cyclophosphamide, Cytarabine, Methotrexate, 6-M...
- Sponsor
- St. Jude Children's Research Hospital
Who can join
- Age
- 1 to 18 years
- Sex
- All sexes
- Healthy volunteers
- Not accepted
Inclusion 29
- Minimum age: 1 years
- Maximum age: 18 years
- Study condition: Acute Lymphoblastic Leukemia, Lymphoblastic Lymphoma
- 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:
- Total bilirubin ≤ 1.5x the upper limit of normal for age and alanine transaminase (ALT) ≤ 5x the upper limit of normal for age. Patients with an elevated total bilirubin due to hemolysis are eligible if they have a direct bilirubin \<1.5x the upper limit of normal.
- 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.
- These patients may receive no more than 2 weeks of post-induction therapy and should be transitioned to SJALL23H post-induction as soon as the qualifying genetic or MRD result is available.
Exclusion 10
- 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.
Where
3 sites, 3 recruiting
Novant Health Presbyterian Hemby Children's Hospital
Charlotte, North Carolina, United States
St. Jude Children's Research Hospital
Memphis, Tennessee, United States
Saint Francis Children's Hospital
Tulsa, Oklahoma, United States
Contact
-
Seth E. Karol, MD, MSCI
888-226-4343 referralinfo@stjude.org
Potential match only. Final eligibility is determined by the study team.