This phase II trial studies how well inotuzumab ozogamicin and blinatumomab with or without ponatinib work in treating patients with CD22-positive B-lineage acute lymphoblastic leukemia that is newly diagnosed, has come back after a period of improvement (recurrent), or does not respond to treatment (refractory). Inotuzumab ozogamicin is a monoclonal antibody, called inotuzumab, linked to a chemotherapy drug, called ozogamicin. Inotuzumab is a form of targeted therapy because it attaches to specific molecules (receptors) on the surface of cancer cells, known as CD22 receptors, and delivers ozogamicin to kill them. Blinatumomab is a monoclonal antibody that may interfere with the ability of cancer cells to grow and spread. A monoclonal antibody is a type of protein that can bind to certain targets in the body, such as molecules that cause the body to make an immune response (antigens). Ponatinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving inotuzumab ozogamicin and blinatumomab with or without ponatinib may be effective in treating patients with newly diagnosed, recurrent or refractory CD22 positive B-lineage acute lymphoblastic leukemia.
STEP 0: Submission of bone marrow aspirate and peripheral blood for MRD analysis is mandatory prior to registration; the bone marrow sample should be from the first aspiration (i.e. first pull). Aspirate needle should be redirected if needed to get first pull bone marrow aspirate. It should be initiated as soon as possible after pre-registration. The specimens should be sent to the HEME Biobank.
Patients may receive the day 1 of course IA dose of intrathecal (IT) methotrexate during the prior-to-registration lumbar puncture (or the venous line placement) to avoid a second lumbar puncture. If the dose is administered prior to registration, then systemic chemotherapy must begin within 7 days of this IT chemotherapy.
STEP 1: Morphologic diagnosis of precursor B-cell acute lymphoblastic leukemia (ALL) based on World Health Organization (WHO) criteria. Patients with Burkitt lymphoma/leukemia are not eligible.
STEP 1: CD22-positive disease defined as CD22 expression by >= 20% of lymphoblasts by local hematopathology evaluation.
None
Parallel
Biospecimen Collection
Procedure/SurgeryUndergo blood sample and cerebrospinal fluid collection
Blinatumomab
Biological/VaccineGiven IV
Bone Marrow Aspiration
Procedure/SurgeryUndergo bone marrow aspiration
Bone Marrow Biopsy
Procedure/SurgeryUndergo bone marrow biopsy
Inotuzumab Ozogamicin
Biological/VaccineGiven IV
Lumbar Puncture
Procedure/SurgeryUndergo lumbar puncture
Ponatinib
DrugGiven PO
Event-free survival
Will be defined as time from start of treatment to failure to achieve complete response (CR)/complete response with incomplete count recovery (CRi) after completing Course II of blinatumomab, relapse after CR/CRi, progression on study requiring withdrawal from study therapy, or death from any cause
Completion of protocol treatment (cohort 3)
Feasibility defined as completion of the planned therapy as defined in the protocol. Success rate defined as the proportion of patients who either complete entire protocol treatment or go off protocol treatment due to the disease (e.g., refractory disease, progression, and relapse).
Overall survival (OS)
Will be evaluated using the Kaplan-Meier method. A 95% confidence interval for the 1- and 3-year rates will be constructed using a point-wise confidence interval for the survival function based on a log-minus-log transformation. Will also calculate a 95% confidence interval by using a point-wise confidence interval for the survival function based on a log-minus-log transformation.
Relapse-free survival (RFS)
Will be evaluated using the Kaplan-Meier method. A 95% confidence interval for the 1- and 3-year rates will be constructed using a point-wise confidence interval for the survival function based on a log-minus-log transformation. Will also calculate a 95% confidence interval by using a point-wise confidence interval for the survival function based on a log-minus-log transformation.
Event-free survival (EFS)
Will be evaluated using the Kaplan-Meier method. A 95% confidence interval for the 1- and 3-year rates will be constructed using a point-wise confidence interval for the survival function based on a log-minus-log transformation. Will also calculate a 95% confidence interval by using a point-wise confidence interval for the survival function based on a log-minus-log transformation.
Complete and overall response rate
Point and interval estimates of the rates will be shown using a 95% binomial confidence interval.
Rate of cytokine release syndrome (Cohort 1)
Point and interval estimates of the rate will be shown using a 95% binomial confidence interval.
Sinusoidal obstruction syndrome/veno-occlusive disease (SOS/VOD) of the liver
The rate of, timing of, and risk factors for SOS/VOD of the liver after limited inotuzumab ozogamicin exposure. Point and interval estimates of the rate will be shown using a 95% binomial confidence interval. A summary of the timing and risk factors for SOS/VOD of the liver will be provided.
OS
Will compare between patients achieving CR/CRi and receiving consolidation with allogeneic hematopoietic cell transplantation versus (vs.) patients achieving CR/CRi and receiving consolidation without allogeneic hematopoietic cell transplantation. The median, 1-year, and 2-year OS will be compared between the above two groups. The distribution of OS for each group will be estimated using the Kaplan-Meier method.
RFS
Will compare between patients achieving CR/CRi and receiving consolidation with allogeneic hematopoietic cell transplantation vs. patients achieving CR/CRi and receiving consolidation without allogeneic hematopoietic cell transplantation. The median, 1-year, and 2-year RFS will be compared between the above two groups. The distribution of RFS for each treatment arm will be estimated using the Kaplan-Meier method.
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