Madera

Researchers are evaluating a new vaccine called V118C designed to prevent pneumococcal disease, which includes infections caused by the Streptococcus pneumoniae bacteria. This study focuses on toddlers and infants to understand the safety and tolerance of V118C. It is a Phase 1 trial that compares V118C to an existing pneumococcal vaccine called PCV20 in children. The study has two parts: Stage 1 involves toddlers aged 12 to 15 months who have already received three doses of PCV20 during infancy. Stage 2 involves infants around 2 months old who will receive four doses of V118C using a 3+1 schedule (three infant doses plus one toddler dose). Both vaccines are given by intramuscular injection. The study compares safety and immune response between V118C and PCV20. Participants will be monitored for immediate reactions within 30 minutes after vaccination and for local and systemic side effects up to 7 days post-vaccination. Unsolicited adverse events will be tracked up to 28 days, and serious or medically attended events will be assessed for up to 12 months after vaccination. The study aims to collect detailed safety and tolerability information over this period.

Researchers are evaluating a culturally-tailored, home-based physical activity program designed to improve physical fitness in Hispanic or Latino/Latina adolescent and young adult childhood cancer survivors. These survivors may face long-term effects such as weight gain, fatigue, and reduced fitness after cancer treatment, with Hispanic or Latino/Latina individuals potentially at higher risk. The study aims to increase moderate to vigorous physical activity (MVPA) through a mobile health and social media intervention. The study has two stages. Stage 1 involves developing the intervention using feedback from 20 Latinx survivors who speak either English or Spanish. Stage 2 is a randomized controlled trial comparing the intervention group with a control group that only uses a Fitbit tracker. The intervention group receives Fitbit trackers, weekly reminders, goal-setting sessions, social media peer support 2-3 times a week, badges, monthly Zoom meetings, and may choose a physical activity partner who also receives support. After 12 weeks, a 4-week maintenance phase continues these supports with less structure. The control group wears a Fitbit daily for 12 weeks without additional support. Participants wear Fitbit trackers daily, attend weekly sessions, post on social media, and complete interviews and questionnaires. Researchers measure changes in physical activity levels, sedentary time, quality of life, and cardiometabolic health indicators. Data is collected using Fitbit devices, interviews, and surveys, with follow-up over 12 weeks plus maintenance. Safety and acceptability of the intervention are also assessed throughout the study.

Researchers are evaluating the efficacy and safety of benralizumab, given as a subcutaneous injection, in children and adolescents aged 6 to under 18 years who have severe eosinophilic asthma. These patients have a history of asthma exacerbations and uncontrolled symptoms despite treatment with high-dose inhaled corticosteroids plus at least one other controller medication. This Phase III study aims to compare benralizumab to placebo in reducing the time to the first asthma exacerbation. The study includes a screening period lasting from 4 to 12 weeks to confirm eligibility. After screening, patients are randomly assigned in a 1:1 ratio to receive either benralizumab or placebo via subcutaneous injections during a double-blind treatment period lasting a minimum of 16 weeks. This period continues until the patient experiences an asthma exacerbation or a set number of events occur. Patients who exacerbate can enter an open-label extension where all receive benralizumab for at least 48 weeks. An end-of-treatment visit occurs 8 weeks after the last dose in the extension phase. Participants will be monitored through visits and assessments including confirmation of severe eosinophilic asthma, asthma control questionnaires, and symptom diaries. Researchers will measure the time to first asthma exacerbation as the primary outcome. Medication adherence is tracked during screening, and safety is monitored throughout both the double-blind and extension periods. Total participation may span over a year, considering screening, treatment, extension, and follow-up visits.

Researchers are evaluating the effectiveness and safety of risdiplam in young children under 2 years old diagnosed with spinal muscular atrophy (SMA) who have two copies of the SMN2 gene and have previously received gene therapy with onasemnogene abeparvovec but have experienced a plateau or decline in function. This is an open-label, single-arm, multicenter Phase IV study focusing on this specific pediatric population with SMA. The study aims to assess how risdiplam may impact motor development and overall function after gene therapy. Participants will receive risdiplam orally at doses adjusted according to their weight and age. The treatment is given during the study period, with the dose tailored to each child's characteristics. This study does not include a comparator group and monitors the participants over a treatment period of 72 weeks. The intervention involves continuous administration of risdiplam, and the study design allows observation of changes in motor function following prior gene therapy. During the study, children will be closely monitored through various assessments, including the Bayley Scales of Infant and Toddler Development to measure gross motor skills at baseline and after 72 weeks of treatment. Researchers will track changes in motor abilities, swallowing, respiratory function, and other developmental milestones. Safety evaluations and laboratory tests will be conducted throughout the study to ensure participant well-being. The total duration of participation includes treatment and follow-up visits over the 72-week period.

Researchers are investigating the best way to combine chemotherapy and radiation therapy based on how patients with localized non-germinomatous germ cell tumors (NGGCT) in the brain respond to initial chemotherapy. This phase II study aims to optimize radiation treatment for those who respond well to induction chemotherapy to reduce spinal cord relapses, and to use higher dose chemotherapy followed by conventional radiation for patients who do not respond as well. The study evaluates various chemotherapy drugs that work to stop tumor growth in different ways and uses radiation therapy with high-energy x-rays or protons to kill tumor cells and shrink tumors. Participants receive induction chemotherapy with drugs including carboplatin, etoposide, ifosfamide, and thiotepa over multiple cycles. Based on their response, patients are assigned to one of two treatment plans: those with a good response receive whole ventricular plus spinal canal irradiation (WVSCI) radiation therapy, while those with less favorable responses may receive high-dose chemotherapy with peripheral blood stem cell transplantation followed by radiation therapy. Some patients may also undergo second-look surgery depending on their tumor response. Treatments are carefully scheduled and monitored for up to six weeks for radiation and multiple cycles for chemotherapy. During the study, participants undergo regular assessments including MRI scans, cerebrospinal fluid and blood sample collections, and neurocognitive and quality of life evaluations. Researchers monitor tumor response, progression-free survival, overall survival, and treatment side effects for up to 10 years after treatment. Additional evaluations compare outcomes based on radiation type and assess growth and blood counts in younger patients. Patient safety and treatment effectiveness are closely followed throughout the study period.

Researchers are evaluating combination chemotherapy treatments for patients with newly diagnosed stage II-IV diffuse anaplastic Wilms tumors (DAWT) and relapsed favorable histology Wilms tumors (FHWT). This phase II trial aims to assess how adding vincristine and irinotecan to standard chemotherapy regimens affects event-free survival and overall survival compared to historical data. The study also explores kidney toxicity, tumor genetics, and radiation therapy techniques to reduce side effects in children with lung and liver metastases. Two chemotherapy regimens are studied. Arm I (Regimen UH-3) involves cycles of vincristine, doxorubicin, cyclophosphamide, carboplatin, etoposide, and irinotecan given intravenously on specific days every 21 days. Radiation therapy is given around week 7 of cycle 3 if needed. Arm II (Regimen ICE/Cyclo/Topo) includes cycles of ifosfamide, carboplatin, etoposide, cyclophosphamide, and topotecan given intravenously every 21 days, with surgery and/or radiation during certain cycles. Both arms include multiple cycles in absence of disease progression or unacceptable side effects. Participants undergo various scans like CT, PET, MRI, chest x-rays, ultrasounds, and bone scans throughout the trial. Blood samples and biopsies may be collected periodically. After treatment, patients are followed up every 3 months for the first 2 years, every 6 months for years 3-4, and once at year 5. The main outcomes measured are event-free survival and overall survival up to 5 years, along with monitoring kidney health and treatment effects.

Researchers are investigating treatments for children and young adults aged 4 to 21 with low-risk and average-risk medulloblastoma, a type of brain cancer. The study evaluates whether adding sodium thiosulfate (STS) to standard chemotherapy and radiation reduces hearing loss caused by cisplatin in average-risk patients. It also examines if using less intense radiation can provide similar benefits with fewer side effects in low-risk patients. The trial aims to ensure survival rates and cancer recurrence are not negatively affected by these approaches. Participants receive radiation therapy five days a week for six weeks alongside weekly vincristine infusions, followed by maintenance therapy beginning four weeks later. Maintenance includes cycles of oral lomustine, intravenous cisplatin and sodium thiosulfate, and intravenous cyclophosphamide and vincristine, repeated over multiple cycles without disease progression or unacceptable side effects. The study also involves MRI scans, cerebrospinal fluid and optional blood sample collection throughout treatment. During the study, participants undergo hearing tests, cognitive and quality-of-life assessments, and monitoring for side effects like kidney damage. Researchers track hearing loss, event-free survival, overall survival, and tumor recurrence for up to 10 years after treatment. Follow-up visits occur every three months for the first two years, then less frequently through year ten to monitor long-term outcomes.

Researchers are evaluating the combination of blinatumomab with dasatinib or imatinib alongside standard chemotherapy to treat patients with Philadelphia chromosome-positive (Ph+) or ABL-class Philadelphia chromosome-like (Ph-like) B-cell acute lymphoblastic leukemia (B-ALL). This phase 2 trial focuses on children, adolescents, and young adults under 25 years with newly diagnosed Ph+ or ABL-class Ph-like B-ALL, aiming to estimate three-year event-free survival (EFS) and assess safety and toxicity of this chemo-immunotherapy approach. Treatment involves a modified Berlin-Frankfurt-Mfcnster chemotherapy backbone with three cycles of blinatumomab replacing traditional consolidation chemotherapy. Patients with Ph+ B-ALL receive continuous dasatinib, while those with ABL-class Ph-like B-ALL receive continuous imatinib or dasatinib depending on specific gene fusions. The study includes multiple treatment phases: induction, blinatumomab blocks, interim maintenance, delayed intensification, and maintenance cycles repeated every 12 weeks for two years, with some patients possibly receiving radiation therapy. Participants undergo blood and cerebrospinal fluid sample collections, bone marrow biopsies, echocardiography or multigated acquisition scans, and various laboratory tests throughout the study. Researchers measure outcomes such as three-year event-free survival, incidence of adverse events, minimal residual disease negativity, treatment response, and overall survival. Safety monitoring includes assessments of infections, neurotoxicity, and therapy-related mortality. The total participation extends up to three years with ongoing evaluations to track treatment effects and side effects.

PRIMARY OBJECTIVES: I. To compare event free survival post reinduction (EFS PR) between blinatumomab vs. blinatumomab/nivolumab in Group 4 patients aged ≥ 1 to \<31 years old with first relapse of CD19+ B ALL. II. To compare EFS PR (EFS post-reinduction) between consolidation with blinatumomab vs. blinatumomab/nivolumab in Group 3 patients aged \>= 1 to \< 31 years old with first relapse of CD19+ B ALL. SECONDARY OBJECTIVES: I. To evaluate the safety and tolerability of blinatumomab/nivolumab in patients aged \>= 1 to \< 31 years old with first relapse of CD19+ B ALL. EXPLORATORY OBJECTIVES: I. In Group 4 patients, compare EFS PR between blinatumomab monotherapy and blinatumomab/nivolumab arms as compared to similar patients treated on the predecessor trial AALL1331. II. In Group 4 patients, compare toxicity as defined by grade 3 or greater adverse events during the first cycle of blinatumomab or blinatumomab/nivolumab. III. In Group 4 patients, compare MRD negative second remission (Rem-2) rate after the first cycle of immunotherapy between blinatumomab monotherapy and blinatumomab/nivolumab arms. IV. In patients with Down syndrome (DS) with first relapse of B-ALL, describe the safety, tolerability and efficacy (as defined by MRD negative second remission, Rem-2) after up to two cycles of blinatumomab/nivolumab. V. With each Group, perform subset analyses of EFS and overall survival (OS) based on features including degree of marrow disease at relapse, age, sex, body mass index, cytogenetics, site(s) of relapse, percent peripheral blasts at relapse and absolute lymphocyte count at first relapse. OUTLINE: Patients \>= 18 years old with marrow +/- extramedullary (EM) relapse of any duration after initial diagnosis, or patients \< 18 years old with marrow +/- EM relapse \< 24 months after initial diagnosis are assigned to Group 1. Patients \< 18 years old with marrow +/- EM relapse \>= 24 months from initial diagnosis, or all isolated extramedullary (IEM) relapses \>= 1 to \< 31 years old are assigned to Groups 2-3 re-induction. Patients with DS are assigned to Arm G. NOTE: Patients in Group 1 and DS patients with white blood cells (WBC) \>= 30,000/uL, CNS 2/3 disease, or testicular disease must first receive 1 of 3 pre-immunotherapy treatments. Starting with amendment 4C (9/19/2024), patients with DS are assigned to group 3 or 4. Patients \< 18 years with bone marrow first relapse ≥ 36 months from initial diagnosis with MRD \<0.1% after VXLD reinduction or with isolated CNS/testicular extramedullary relapse occurring ≥ 18 months from initial diagnosis with MRD \<0.1% after VXLD reinduction are assigned to group 3. Patients who do not meet criteria for group 3 will be assigned to group 4. Patients with Down syndrome ≥ 1 to \< 31 years of age with first bone marrow relapse of B ALL are assigned to arm G. PRE-IMMUNOTHERAPY TREATMENT FOR PATIENTS WITH WBC \>= 30,000/uL (CLOSED TO ACCRUAL 9/19/2024 EXCEPT FOR ARM G) : Patients receive methotrexate (MTX) intrathecally (IT) or cytarabine IT or intrathecal triple therapy (ITT) consisting of MTX, hydrocortisone sodium succinate, and cytarabine IT at the time of diagnostic lumbar puncture (LP) or on day 1 (if intrathecal therapy is given with relapse diagnostic LP \< 7 days prior to the start of protocol therapy). Patients also receive dexamethasone intravenously (IV) or orally (PO) twice daily (BID) on days 1-5, vincristine sulfate via infusion or IV push over 1 minute on day 1. Patients with DS also receive leucovorin calcium PO or IV every 6 hours (q6h) for 2 doses on day 2 or at 24 and 30 hours after each IT administration. Patients should proceed to the next cycle when CNS 1 and no testicular disease is present, no sooner than Day 8 and no later than Day 15. PRE-IMMUNOTHERAPY TREATMENT FOR CNS 2/3 DISEASE (CLOSED TO ACCRUAL 9/19/2024 EXCEPT FOR ARM G): Patients receive MTX IT or cytarabine IT twice weekly (Q2W) for 5-7 doses or Intrathecal Triple Therapy (ITT) IT Q2W for 3-4 doses until patient is CNS 1. Patients with DS also receive leucovorin calcium PO or IV q6h for 2 doses at 24 and 30 hours after each IT administration. Patients should proceed to the next cycle when CNS 1 and no testicular disease is present, no sooner than Day 15 and no later than Day 24. PRE-IMMUNOTHERAPY TREATMENT FOR TESTICULAR DISEASE(CLOSED TO ACCRUAL 9/19/2024 EXCEPT FOR ARM G): Patients receive MTX IT, cytarabine IT, or ITT IT on days 1 and 15 (day 1 may be omitted if intrathecal therapy is given with relapse diagnostic LP \< 7 days prior to the start of protocol therapy). Patients with DS also receive leucovorin calcium PO or IV q6h for 2 doses on days 2 and 16 or at 24 and 30 hours after each IT administration. Males with testicular disease at relapse undergo radiation once daily (QD) for a total of 12 fractions over 12 days. Patients should proceed to the next cycle when CNS 1 and no testicular disease is present, no sooner than Day 15 and no later than Day 22. GROUP 1 (CLOSED TO ACCRUAL 9/19/2024): Patients are randomized to Arm A or Arm B. ARM A: Patients receive dexamethasone PO or IV on days 1 and 8 of cycle 1, blinatumomab via continuous IV infusion on days 1-28 of cycles 1-2, MTX IT, cytarabine IT, or ITT IT on days 1, 15, and 36 of cycle 1 (MTX, cytarabine, and ITT on day 1 may be omitted if intrathecal therapy was given \< 7 days prior to the start of this cycle), and MTX IT, cytarabine IT, or ITT IT on days 15 and 36 of cycle 2. Treatment repeats every 36 days for 2 cycles in the absence of disease progression or unacceptable toxicity. NOTE: Patients with MRD \< 0.01% after cycle 1 may stop study treatment or may choose to continue to cycle 2. Patients with MRD \>= 0.01% after cycle 1 proceed to cycle 2. ARM B: Patients receive dexamethasone, blinatumomab, and MTX, cytarabine, or ITT as in Arm A. Patients also receive nivolumab IV over 30 minutes on days 11 and 25 of cycle 1 and days 1 and 15 of cycle 2. Treatment repeats every 36 days for 2 cycles in the absence of disease progression or unacceptable toxicity. NOTE: Patients with MRD \< 0.01% after cycle 1 may stop study treatment or may choose to continue to cycle 2. Patients with MRD \>= 0.01% after cycle 1 proceed to cycle 2. GROUPS 2-4 VXLD REINDUCTION: Patients receive vincristine sulfate via infusion or IV push over 1 minute on days 1, 8, 15, and 22, dexamethasone PO or IV on days 1-14, doxorubicin hydrochloride IV over 1-15 minutes on day 1, MTX IT on days 1, 8, and 29 (day 1 IT may be omitted if intrathecal therapy is given with relapse diagnostic LP \< 7 days prior to the start of this cycle) (days 8 and 29 for CNS 1 patients at relapse only), pegaspargase intramuscularly (IM) or IV over 1-2 hours on days 2 and 16 or calaspargase IV over 1-2 hours on day 2 (for patients ≤ 22 years), cytarabine IT on days 4 and 11 (CNS 2 patients at relapse only), then Q2W until 3 consecutive samples are clear of blasts, and ITT IT on days 8, 15, 22, and 29 (CNS 3 patients at relapse only). Treatment continues in the absence of disease progression or unacceptable toxicity. GROUP 2 (CLOSED TO ACCRUAL 9/19/2024): The following patients are randomized to Arm C or Arm D: 1) \>= 1 to \< 31 years old, IEM relapse \< 18 months from diagnosis, regardless of MRD after Re-Induction. 2) \< 18 years old with marrow relapse \>= 24 to \< 36 months from diagnosis regardless of MRD after Re-Induction, 3) \>= 1 to \< 31 years old, IEM relapse \>= 18 months, and MRD \>= 0.1% after Re-Induction, 4) \< 18 years old with marrow relapse \>= 36 months, and MRD \>= 0.1% after Re-Induction. ARM C: Patients receive dexamethasone PO or IV on day 1 of cycle 1, blinatumomab via continuous IV infusion on days 1-28 of cycles 1 and 2, and MTX IT on days 1 and 15 of cycles 1 and 2 (day 1 may be omitted from cycle 1 if intrathecal MTX is given \< 7 days prior to the start of cycle 1 ). Treatment repeats every 36 days for 2 cycles in the absence of disease progression or unacceptable toxicity. NOTE: Patients with MRD \< 0.01% after cycle 1 may stop study treatment or may choose to continue to cycle 2. Patients with MRD \>= 0.01% after cycle 1 proceed to cycle 2. ARM D: Patients receive dexamethasone, blinatumomab, and MTX as in Arm C. Patients also receive nivolumab IV over 30 minutes on days 11 and 25 of cycle 1 and days 1 and 15 of cycle 2. Treatment repeats every 36 days for 2 cycles in the absence of disease progression or unacceptable toxicity. NOTE: Patients with MRD \< 0.01% after cycle 1 may stop study treatment or may choose to continue to cycle 2. Patients with MRD \>= 0.01% after cycle 1 proceed to cycle 2. GROUP 3: Patients are randomized to Arm E or Arm F. ARM E: IMMUNOTHERAPY CYCLES 1-2: Patients receive dexamethasone PO or IV on day 1 of cycle 1 only, blinatumomab IV via continuous infusion on days 1-28, and MTX IT on days 1 and 15 (day 1 may be omitted from cycle 1 if intrathecal therapy is given \< 7 days prior to the start of this cycle). Immunotherapy cycles 1-2 alternate with Consolidation cycles 1-2. CONSOLIDATION: Patients receive dexamethasone PO or IV on days 1-5, methotrexate IV, over 24 hours, on days 8 and 22, methotrexate IT on days 8 and 22 (CNS 1/2 at relapse only) or ITT IT on days 8 and 22 (CNS 3 at relapse only). INTENSIFICATION CYCLES 1-2: Patients receive dexamethasone PO on days 1-5, vincristine sulfate IV push over 1 minute or via infusion on day 1, mercaptopurine PO on days 1-42, methotrexate IV over 24 hours on days 8 and 22, cytarabine IV, over 3 hours on days 43 and 44, asparaginase erwinia recombinant IM or crisantaspase/asparaginase erwinia IM or IV over 1-2 hours on day 44, methotrexate IT on days 1 and 43 (CNS 1/2 at relapse only) or ITT IT on days 1 and 43 (CNS 3 at relapse only). IMMUNOTHERAPY CYCLE 3: Patients receive blinatumomab IV via continuous infusion on days 1-28, and MTX IT on days 1 and 15 (CNS 1/2 at relapse only) or ITT IT on days 1 and 15 (CNS 3 at relapse only). MAINTENANCE: Patients receive dexamethasone PO BID on days 1-5, 29-33, and 57-61, vincristine sulfate IV push over 1 minute or via infusion on days 1, 29, and 57, mercaptopurine PO on days 1-84, MTX IT on day 1 (CNS 1/2 patients at relapse only), ITT IT on day 1 (CNS 3 patients at relapse only), and MTX PO on days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78. Treatment repeats every 12 weeks for 2 years from the start of Re-Induction therapy in the absence of disease progression or unacceptable toxicity. MAINTENANCE CHEMORADIATION (FOR CNS 3 PATIENTS ONLY): Beginning between the first and second cycles of maintenance therapy, patients receive dexamethasone PO BID on days 1-7 and 15-21, vincristine sulfate IV push over 1 minute or via infusion on days 1, 8, and 15, and pegaspargase IM or IV over 1-2 hours or calaspargase IV over 1-2 hours on day 1. Patients with CNS 3 and isolated CNS relapse undergo cranial radiation in the form of 3-dimensional (D)-conformal radiation therapy (CRT) over 5 days per week for a total of 10 treatments. ARM F: IMMUNOTHERAPY CYCLES 1-2: Patients receive dexamethasone PO or IV on day 1 of cycle 1 only, blinatumomab IV via continuous infusion on days 1-28, nivolumab IV over 30 minutes on days 11 of cycle 1 and on days 1 of cycles 2 and 3, and MTX IT on days 1 and 15 (CNS 1/2 patients at relapse only)(day 1 may be omitted from cycle 1 if intrathecal therapy is given with \< 7 days prior to the start of this cycle) or , ITT IT on day 1 (CNS 3 patients at relapse only) (day 1 may be omitted from cycle 1 if intrathecal therapy is given with \< 7 days prior to the start of this cycle). Immunotherapy cycles 1-2 alternate with Consolidation cycles 1-2. CONSOLIDATION CYCLES 1-2: Patients receive dexamethasone PO on days 1-5, vincristine sulfate IV push over 1 minute or via infusion on day 1, methotrexate IV, over 24 hours, on days 8 and 22, methotrexate IT on days 8 and 22 (CNS 1/2 at relapse only) or ITT IT on days 8 and 22 (CNS 3 at relapse only). INTENSIFICATION CYCLES 1-2: Patients receive dexamethasone PO on days 1-5, vincristine sulfate IV push over 1 minute or via infusion on day 1, mercaptopurine PO on days 1-42, methotrexate IV over 24 hours on days 8 and 22, cytarabine IV, over 3 hours on days 43 and 44, asparaginase erwinia recombinant IM or crisantaspase/asparaginase erwinia IM or IV over 1-2 hours on day 44, methotrexate IT on days 1 and 43 (CNS 1/2 at relapse only) or ITT IT on days 1 and 43 (CNS 3 at relapse only). IMMUNOTHERAPY CYCLE 3: Patients receive blinatumomab IV via continuous infusion on days 1-28, nivolumab IV over 30 minutes on days 1 and 15 and MTX IT on days 1 and 15. MAINTENANCE: Patients receive dexamethasone PO BID on days 1-5, 29-33, and 57-61, vincristine sulfate IV push over 1 minute or via infusion on days 1, 29, and 57, mercaptopurine PO on days 1-84, MTX IT on day 1 (CNS 1/2 patients at relapse only), ITT IT on day 1 (CNS 3 patients at relapse only), and MTX PO on days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, 78. Treatment repeats every 12 weeks for 2 years from the start of Re-Induction therapy in the absence of disease progression or unacceptable toxicity. MAINTENANCE CHEMORADIATION (FOR CNS 3 PATIENTS): Beginning between the first and second cycles of maintenance therapy, patients receive dexamethasone PO BID on days 1-7 and 15-21, vincristine sulfate IV push over 1 minute or via infusion on days 1, 8, and 15, and pegaspargase IM or IV over 1-2 hours or calaspargase IV over 1-2 hours on day 1. Patients with CNS 3 and isolated CNS relapse undergo cranial radiation in the form of 3-dimensional (D)-conformal radiation therapy (CRT) over 5 days per week for a total of 10 treatments. GROUP 4: Patients are randomized to arm H or arm I. ARM H: Patients receive dexamethasone PO or IV on day 1 and 8 of cycle 1 only, blinatumomab IV via continuous infusion on days 1-28 and MTX IT on days 1 of cycle 1 only and days 15 and 36 ( for patients with CNS1/2 at relapse only) or ITT on day 1 of cycle 1 only and days 15 and 36 (for patients with CNS 3 at relapse only) (day 1 IT therapy may be omitted from cycle 1 if intrathecal therapy is given with \< 7 days prior to the start of this cycle). Cycles repeat every 36 days for up to 2 cycles in the absence of disease progression or unacceptable toxicity. ARM I: Patients receive dexamethasone PO or IV on day 1 and 8 of cycle 1 only, blinatumomab IV via continuous infusion on days 1-28, nivolumab IV, over 30 minutes on day 11 of cycle 1 and day 3 of cycle 2 and MTX IT on days 1 of cycle 1 only and days 15 and 36 ( for patients with CNS 1/2 at relapse only) or ITT on day 1 of cycle 1 only and days 15 and 36 (for patients with CNS 3 at relapse only) (day 1 IT therapy may be omitted from cycle 1 if intrathecal therapy is given with \< 7 days prior to the start of this cycle). Cycles repeat every 36 days for up to 2 cycles in the absence of disease progression or unacceptable toxicity. ARM G (DS PATIENTS): Patients receive dexamethasone PO or IV on days 1 and 8 of cycle 1 only, blinatumomab IV via continuous infusion on days 1-28, nivolumab IV over 30 minutes on days 11 of cycle 1 and day 3 of cycle 2, and MTX IT (for patients with CNS 1/2 at relapse only) or ITT on day 1 of cycle 1 only and days 15 and 36 (for patients with CNS 3 at relapse only) (day 1 IT therapy may be omitted from cycle 1 if intrathecal therapy is given with \< 7 days prior to the start of this cycle). Cycles repeat every 37 days for up to 2 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo lumbar puncture, bone marrow biopsy and aspiration, and collection of blood, urine and cerebrospinal fluid throughout the study. After completion of study treatment, patients are followed up every 3 months for 1 year.

Researchers are evaluating treatments for children and young adults with newly diagnosed acute myeloid leukemia (AML), with or without FLT3 gene mutations. This phase III trial compares standard chemotherapy using daunorubicin, cytarabine, and gemtuzumab ozogamicin to therapy with liposome-encapsulated daunorubicin-cytarabine (CPX-351) and/or the FLT3 inhibitor gilteritinib. The study aims to find out which treatment improves event-free survival, overall survival, and minimal residual disease rates, while also monitoring heart function and other effects during and after therapy. Participants are assigned to different treatment arms based on their AML risk group and FLT3 mutation status. Treatments include combinations of intravenous and intrathecal chemotherapy drugs such as cytarabine, daunorubicin, gemtuzumab ozogamicin, dexrazoxane, etoposide, mitoxantrone, asparaginase, and methotrexate. Gilteritinib is given orally to patients with FLT3 mutations alongside chemotherapy. Treatment phases include multiple induction cycles, intensification cycles, and for some, allogeneic stem cell transplantation followed by maintenance therapy with gilteritinib. Throughout the study, participants undergo regular assessments including blood tests, bone marrow biopsies, imaging scans like MRI and CT, cardiac function monitoring, and neuropsychological testing. Researchers track event-free survival up to 3 years, changes in heart function, leukemia response, and neurocognitive effects. Optional cognitive tests are offered at several time points. The study also collects blood samples for pharmacokinetic and biomarker analyses to better understand treatment effects and safety.