Brief Summary
This phase III trial studies whether inotuzumab ozogamicin added to post-induction chemotherapya cancer treatment that uses drugs to kill or slow the growth of cancer cells, while minimising damage to healthy cells for patients with High-Risk B-cell Acutenew, recent, comes with an urgent or significant sense, is sudden, sharp Lymphoblastic Leukemia (B-ALL) improves outcomes. This trial also studies the outcomes of patients with mixed phenotype acute leukemia (MPAL), and B-lymphoblastic lymphomacancers of the lymphatic system (B-LLy) when treated with ALL therapy without inotuzumab ozogamicin. Inotuzumab ozogamicin is a monoclonal antibodya protein made by the immune system to fight against harmful substances (antigens), such as bacteria or viruses, called inotuzumab, linked to a type of chemotherapy called calicheamicin. Inotuzumab attaches to cancera disease where abnormal cells split without control and spread to other nearby body tissue and/or organs cellsthe basic structural and functional unit of all living things in a targeted way and delivers calicheamicin to kill them. Other drugs used in the chemotherapy regimen, such as cyclophosphamide, cytarabine, dexamethasone, doxorubicin, daunorubicin, methotrexate, leucovorin, mercaptopurine, prednisone, thioguanine, vincristine, and pegaspargase or calaspargase pegol work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. This trial will also study the outcomes of patients with mixed phenotype acute leukemia (MPAL) and disseminated B lymphoblastic lymphoma (B-LLy) when treated with high-risk ALL chemotherapy.
The overall goal of this study is to understand if adding inotuzumab ozogamicin to standard of care chemotherapy maintains or improves outcomes in High Riskthe possibility that something bad will happen B-cell Acute Lymphoblastic Leukemia (HR B-ALL). The first part of the study includes the first two phases of therapy: Induction and Consolidation. This part will collect information on the leukemia, as well as the effects of the initial treatment, to classify patients into post-consolidation treatment groups. On the second part of this study, patients with HR B-ALL will receive the remainder of the chemotherapy cycles (interim maintenance I, delayed intensification, interim maintenance II, maintenance), with some patients randomized to receive inotuzumab. The patients that receive inotuzumab will not receive part of delayed intensification. Other aims of this study include investigating whether treating both males and females with the same duration of chemotherapy maintains outcomes for males who have previously been treated for an additional year compared to girls, as well as to evaluate the best ways to help patients adhere to oral chemotherapy regimens. Finally, this study will be the first to track the outcomes of subjects with disseminated B-cell Lymphoblastic Leukemia (B-LLy) or Mixed Phenotype Acute Leukemia (MPAL) when treated with B-ALL chemotherapy.
Intervention / Treatment
- Procedure: Biospecimen Collection
- Procedure: Bone Marrow Aspirationa procedure that involves inserting a needle into the hipbone (or the breastbone in some cases) to remove samples of solid and liquid bone marrow.
- Procedure: Bone Marrowsoft, spongy tissue found in bones that makes blood cells Biopsyremoval of a section of tissue to analyse for cancer cells
- Procedure: Bone Scana type of medical imaging that uses a radioactive tracer to detect bone conditions or abnormalities
- Drug: Calaspargase Pegol
- Procedure: Computed Tomography
- Drug: Cyclophosphamide
- Drug: Cytarabine
- Drug: Daunorubicin Hydrochloride
- Drug: Dexamethasone
- Drug: Doxorubicin Hydrochloride
- Biological: Inotuzumab Ozogamicin
- Drug: Leucovorin Calcium
- Procedure: Magnetic Resonance Imagingtests that create detailed images of areas inside the body
- Drug: Mercaptopurine
- Drug: Methotrexate
- Drug: Pegaspargase
- Procedure: Positron Emission Tomography
- Drug: Prednisolone
- Other: Questionnaire Administration
- Radiation: Radiation Therapya treatment that uses controlled doses of radiation to damage or kill cancer cells
- Radiation: Radiation Therapy
- Drug: Thioguanine
- Drug: Vincristine Sulfate
Inclusion Criteria
- B-ALL and MPAL patients must be enrolled on APEC14B1 and consented to eligibility studies (Part A) prior to treatment and enrollment on AALL1732. Note that central confirmation of MPAL diagnosisthe process of identifying a disease based on signs and symptoms, patient history and medical test results must occur within 22 days of enrollment for suspected MPAL patients. If not performed within this time frame, patients will be taken off protocol.
- APEC14B1 is not a requirement for B-LLy patients but for institutional compliance every patient should be offered participation in APEC14B1. B-LLy patients may directly enroll on AALL1732.
- Patients must be > 365 days and < 25 years of age
- White bloodthe red bodily fluid that transports oxygen and other nutrients around the body cell count (WBC) criteria for patients with B-ALL (within 7 days prior to the start of protocol-directed systemic therapy):
- Age 1-9.99 years: WBC >= 50,000/uL
- Age 10-24.99 years: Any WBC
- Age 1-9.99 years: WBC < 50,000/uL with:
- Testicular leukemia
- CNS leukemia (CNS3)
- Steroid pretreatment.
- White blood cell count (WBC) criteria for patients with MPAL (within 7 days prior to the start of protocol-directed systemic therapy):
- Age 1-24.99 years: any WBC NOTE: Patients enrolled as suspected MPAL but found on central confirmatory testing to have B-ALL must meet the B-ALL criteria above (age, WBC, extramedullary disease, steroid pretreatment) to switch to the B-ALL stratum before the end of induction.
- Patient has newly diagnosed B-ALL or MPAL (by World Health Organization [WHO] 2016 criteria) with >= 25% blasts on a bone marrow (BM) aspirateto draw out fluid or tissue from the body, often with a syringe;
- OR If a BM aspirate is not obtained or is not diagnostic of acute leukemia, the diagnosis can be established by a pathologic diagnosis of acute leukemia on a BM biopsy;
- OR A complete blood counta test that counts red blood cells, white blood cells and platelets in the blood (CBC) documenting the presence of at least 1,000/uL circulating leukemic cells if a bone marrow aspirate or biopsy cannot be performed.
- Patient has newly diagnosed B-LLy Murphy stages III or IV.
- Patient has newly diagnosed B-LLy Murphy stages I or II with steroid pretreatment.
- Note: For B-LLy patients with tissuea group of cells that work together to perform a function available for flow cytometry, the criterion for diagnosis should be analogous to B-ALL. For tissue processed by other means (i.e., paraffin blocks), the methodology and criteria for immunophenotypic analysis to establish the diagnosis of B-LLy defined by the submitting institution will be accepted.
- Central nervous system (CNS) status must be determined prior to enrollment based on a sample obtained prior to administration of any systemic or intrathecal chemotherapy, except for steroid pretreatment and cytoreductionremoval of as much of the tumour as possible when complete tumour removal is not possible, also known as tumour debulking. It is recommended that intrathecal cytarabine be administered at the time of the diagnostic lumbar puncturea procedure that involves inserting a needle between two vertebrae in the lower spine and extracting a sample of cerebrospinal fluid (CSF) for analysis. This is usually done at the time of the diagnostic bone marrow or venous line placement to avoid a second lumbar puncture. This is allowed prior to enrollment. Systemic chemotherapy must begin within 72 hours of this intrathecal therapy.
- All patients and/or their parents or legal guardians must sign a written informed consenta process in which a patient receives detailed information about a procedure or treatment, including its potential risks, benefits, and alternatives. The patient then has the opportunity to understand the information and voluntarily agree to the procedure or treatment..
- All institutional, Food and Drug Administration (FDA), and NCI requirements for human studies must be met.